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Keyword: noradrenaline
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Articles
Marcel Ruzicka, John S. Floras, Andrew J. G. McReynolds, Elizabeth Coletta, Haissam Haddad, Ross Davies, Frans H. H. Leenen
Clin Sci (Lond) (2013) 124 (9): 589-595.
Published: 21 January 2013
.... Compared with 50 mg daily, losartan 200 mg/day decreased MSNA significantly ( P <0.05), by approximately 15 bursts/min, and increased MSNA variability within the 0.27–0.33 Hz high-frequency range by 0.11 units 2 /Hz ( P =0.06). PNE [plasma noradrenaline (norepinephrine)] fell in parallel with changes in...
Abstract
In patients with CHF (chronic heart failure) sympathetic activity increases as cardiac performance decreases and filling pressures increase. We hypothesized that in patients with mild-to-moderate CHF, higher than conventional doses of an AT 1 -receptor [AngII (angiotensin II) type 1 receptor] antagonist would achieve greater central AT 1 -receptor blockade, resulting in diminished MSNA (muscle sympathetic nerve activity) and augmented MSNA variability, two indices of central effects on sympathetic outflow. In total, 13 patients with ischaemic cardiomyopathy [NYHA (New York Heart Association) class II–III] were weaned off all pharmacological RAS (renin–angiotensin system) modifiers, and then randomized to receive a low (50 mg/day) or high (200 mg/day) dose of losartan. Central haemodynamics, MSNA and its variability, plasma catecholamines, AngI (angiotensin I) and AngII and aldosterone were assessed both before and 3 months after randomization. Neither dose altered BP (blood pressure), PCWP (pulmonary capillary wedge pressure) or CI (cardiac index) significantly. Compared with 50 mg daily, losartan 200 mg/day decreased MSNA significantly ( P <0.05), by approximately 15 bursts/min, and increased MSNA variability within the 0.27–0.33 Hz high-frequency range by 0.11 units 2 /Hz ( P =0.06). PNE [plasma noradrenaline (norepinephrine)] fell in parallel with changes in MSNA ( r =0.62; P <0.05). These findings support the hypothesis that higher than conventional doses of lipophilic ARBs (AT 1 -receptor blockers) can modulate the intensity and variability of central sympathetic outflow in patients with CHF. The efficacy and safety of this conceptual change in the therapeutic approach to heart failure merits prospective testing in clinical trials.
Articles
Esther Sastre, Gloria Balfagón, Elena Revuelta-López, Maria-Ángeles Aller, Maria-Paz Nava, Jaime Arias, Javier Blanco-Rivero
Clin Sci (Lond) (2012) 122 (7): 337-348.
Published: 07 December 2011
... methyl ester) and the CGRP (calcitonin gene-related peptide) receptor antagonist CGRP-(8–37) in mesenteric segments from ST (short-term; 1 month) and LT (long-term; 21 months) SO (sham-operated) and pre-hepatic PH (portal hypertensive) rats. The vasomotor responses to NA (noradrenaline), the NO donor DEA...
Abstract
In the present study, we analysed possible alterations in adrenergic, nitrergic and sensory functioning in mesenteric arteries from rats at 1 and 21 months after partial portal vein ligation, and the mechanisms involved in these alterations, if any. For this purpose, we analysed the vasoconstrictor response to EFS (electrical field stimulation) and the effect of the α-antagonist phentolamine, the NOS (nitric oxide synthase) inhibitor L -NAME ( N G -nitro- L -arginine methyl ester) and the CGRP (calcitonin gene-related peptide) receptor antagonist CGRP-(8–37) in mesenteric segments from ST (short-term; 1 month) and LT (long-term; 21 months) SO (sham-operated) and pre-hepatic PH (portal hypertensive) rats. The vasomotor responses to NA (noradrenaline), the NO donor DEA-NO (diethylamine NONOate) and CGRP were analysed. NA, NO and CGRP releases were measured. Phospho-nNOS (neuronal NOS) expression was studied. The vasoconstrictor response to EFS was decreased in STPH animals. Phentolamine decreased this vasoconstrictor response more strongly in SO animals. Both L -NAME and CGRP-(8–37) increased vasoconstrictor response to EFS more strongly in PH than SO segments. PH did not modify vasomotor responses to NA, DEA-NO or CGRP, but it decreased NA release while increasing those of NO and CGRP. Phospho-nNOS expression was increased by PH. In LTPH, no differences were observed in vasoconstrictor response to EFS, vasomotor responses or neurotransmitter release when compared with age-matched SO animals. In conclusion, the mesenteric innervation may participate in the development of the characteristic hyperdynamic circulation observed in STPH through the joint action of decreased adrenergic influence, and increased nitrergic and sensory innervations influences. The participation of each innervation normalizes under conditions of LTPH.
Articles
Clin Sci (Lond) (2011) 121 (8): 331-341.
Published: 24 June 2011
... the mechanisms involved. Rats were divided into two groups: (i) control, and (ii) HgCl 2 -treated rats (30 days; first dose, 4.6 μg/kg of body weight; subsequent dose, 0.07 μg·kg −1 of body weight·day −1 , intramuscularly). Vasomotor response to EFS (electrical field stimulation), NA (noradrenaline...
Abstract
In the present study, we have investigated the possible changes in rat mesenteric artery vascular innervation function caused by chronic exposure to low doses of HgCl 2 (mercuric chloride), as well as the mechanisms involved. Rats were divided into two groups: (i) control, and (ii) HgCl 2 -treated rats (30 days; first dose, 4.6 μg/kg of body weight; subsequent dose, 0.07 μg·kg −1 of body weight·day −1 , intramuscularly). Vasomotor response to EFS (electrical field stimulation), NA (noradrenaline) and the NO donor DEA-NO (diethylamine NONOate) were studied, nNOS (neuronal NO synthase) and phospho-nNOS protein expression were analysed, and NO, O 2 − (superoxide anion) and NA release were also determined. EFS-induced contraction was higher in the HgCl 2 -treated group. Phentolamine (1 μmol/l) decreased the response to EFS to a greater extent in HgCl 2 -treated rats. HgCl 2 treatment increased vasoconstrictor response to exogenous NA and NA release. L -NAME ( N G -nitro- L -arginine methyl ester; 0.1 mmol/l) increased the response to EFS in both experimental groups, but the increase was greater in segments from control animals. HgCl 2 treatment decreased NO release and increased O 2 − production. Vasodilator response to DEA-NO was lower in HgCl 2 -treated animals. Tempol increased DEA-NO-induced relaxation to a greater extent in HgCl 2 -treated animals. nNOS expression was similar in arteries from both experimental groups, whereas phospho-nNOS was decreased in segments from HgCl 2 -treated animals. HgCl 2 treatment increased vasoconstrictor response to EFS as a result of, in part, reduced NO bioavailability and increased adrenergic function. These findings offer further evidence that mercury, even at low concentrations, is an environmental risk factor for cardiovascular disease.
Articles
Alberto Giannoni, Michele Emdin, Roberta Poletti, Francesca Bramanti, Concetta Prontera, Massimo Piepoli, Claudio Passino
Clin Sci (Lond) (2008) 114 (7): 489-497.
Published: 29 February 2008
... hypoxia and hypercapnia (i.e. HVR and HCVR), compared with those with normal chemosensitivity, had significantly (all P <0.01) higher noradrenaline (norepinephrine) and BNP (B-type natriuretic peptide) levels, higher prevalence of daytime and night-time CSR, worse NYHA (New York Heart Association...
Abstract
Increased chemosensitivity has been observed in HF (heart failure) and, in order to clarify its pathophysiological and clinical relevance, the aim of the present study was to investigate its impact on neurohormonal balance, breathing pattern, response to exercise and arrhythmic profile. A total of 60 patients with chronic HF [age, 66±1 years; LVEF (left ventricular ejection fraction), 31±1%; values are means±S.E.M.] underwent assessment of HVR (hypoxic ventilatory response) and HCVR (hypercapnic ventilatory response), neurohormonal evaluation, cardiopulmonary test, 24-h ECG monitoring, and assessment of CSR (Cheyne–Stokes respiration) by diurnal and nocturnal polygraphy. A total of 60% of patients had enhanced chemosensitivity. Those with enhanced chemosensitivity to both hypoxia and hypercapnia (i.e. HVR and HCVR), compared with those with normal chemosensitivity, had significantly (all P <0.01) higher noradrenaline (norepinephrine) and BNP (B-type natriuretic peptide) levels, higher prevalence of daytime and night-time CSR, worse NYHA (New York Heart Association) class and ventilatory efficiency [higher V ̇ E (minute ventilation)/ V ̇ CO 2 (carbon dioxide output) slope], and a higher incidence of chronic atrial fibrillation and paroxysmal non-sustained ventricular tachycardia, but no difference in left ventricular volumes or LVEF. A direct correlation was found between HVR or HCVR and noradrenaline ( R =0.40 and R =0.37 respectively; P <0.01), BNP ( R =0.40, P <0.01), N-terminal pro-BNP ( R =0.37 and R =0.41 respectively, P <0.01), apnoea/hypopnoea index ( R =0.57 and R =0.59 respectively, P <0.001) and V ̇ E / V ̇ CO 2 slope ( R =0.42 and R =0.50 respectively, P <0.001). Finally, by multivariate analysis, HCVR was shown to be an independent predictor of both daytime and night-time CSR. In conclusion, increased chemosensitivity to hypoxia and hypercapnia, particularly when combined, is associated with neurohormonal impairment, worse ventilatory efficiency, CSR and a higher incidence of arrhythmias, and probably plays a central pathophysiological role in patients with HF.
Articles
Maria C. P. Franco, Dulce E. Casarini, Marcela S. Carneiro-Ramos, Ana L. Sawaya, Maria L. M. Barreto-Chaves, Ricardo Sesso
Clin Sci (Lond) (2008) 114 (5): 375-380.
Published: 01 February 2008
..., catecholamines and ACE activity were determined in plasma. Circulating noradrenaline levels were significantly elevated in SGA girls compared with AGA girls ( P =0.036). In addition, angiotensin II and ACE activity were higher in SGA boys ( P =0.024 and P =0.050 respectively). There was a significant association...
Abstract
There have been only a few reports on the sympathoadrenal and renin–angiotensin systems in children of small gestational age. The purpose of the present study was to investigate plasma levels of ACE (angiotensin-converting enzyme) activity, angiotensin and catecholamines in 8- to 13-year-old children and to determine whether there are correlations between the components of these systems with both birthweight and BP (blood pressure) levels. This clinical study included 66 children (35 boys and 31 girls) in two groups: those born at term with an appropriate birthweight [AGA (appropriate-for-gestational age) group, n =31] and those born at term but with a small birthweight for gestational age [SGA (small-for-gestational age) group, n =35]. Concentrations of angiotensin, catecholamines and ACE activity were determined in plasma. Circulating noradrenaline levels were significantly elevated in SGA girls compared with AGA girls ( P =0.036). In addition, angiotensin II and ACE activity were higher in SGA boys ( P =0.024 and P =0.050 respectively). There was a significant association of the circulating levels of both angiotensin II and ACE activity with BP levels in our study population. Although the underlying mechanisms that link restricted fetal growth with later cardiovascular events are not fully understood, the findings in the present study support the link between low birthweight and overactivity of both sympathoadrenal and renin–angiotensin systems into later childhood.
Articles
Clin Sci (Lond) (2008) 114 (2): 157-164.
Published: 11 December 2007
...Fatemeh Amirahmadi; Lynne Turnbull; Xiao-Jun Du; Robert M. Graham; Elizabeth A. Woodcock Reperfusion of ischaemic rat or mouse hearts causes NE [noradrenaline (‘norepinephrine’)] release, stimulation of α 1 -ARs (α 1 -adrenergic receptors), PLC (phospholipase C) activation, Ins(1,4,5) P 3...
Abstract
Reperfusion of ischaemic rat or mouse hearts causes NE [noradrenaline (‘norepinephrine’)] release, stimulation of α 1 -ARs (α 1 -adrenergic receptors), PLC (phospholipase C) activation, Ins(1,4,5) P 3 generation and the development of arrhythmias. In the present study, we examined the effect of increased α 1A -AR drive on these responses. In hearts from non-transgenic mice (α 1A -WT), Ins(1,4,5) P 3 generation was observed after 2 min of reperfusion following 30 min of zero-flow ischaemia. No Ins(1,4,5) P 3 response was observed in hearts from transgenic mice with 66-fold overexpression of α 1A -AR (α 1A -TG). This was despite the fact that α 1A -TG hearts had 8–10-fold higher PLC responses to NE than α 1A -WT under normoxic conditions. The immediate phospholipid precursor of Ins(1,4,5) P 3 , PtdIns(4,5) P 2 , responded to ischaemia and reperfusion similarly in α 1A -WT and α 1A -TG mice. Thus the lack of Ins(1,4,5) P 3 generation in α 1A -TG mice is not caused by limited availability of PtdIns(4,5) P 2 . Overall, α 1 -AR-mediated PLC activity was markedly enhanced in α 1A -WT mice under reperfusion conditions, but responses in α 1A -TG mice were not significantly different in normoxia and post-ischaemic reperfusion. Ischaemic preconditioning prevented Ins(1,4,5) P 3 generation after 30 min of ischaemic insult in α 1A -WT mice. However, the precursor lipid PtdIns(4,5) P 2 was also reduced by preconditioning, whereas heightened α 1A -AR activity did not influence PtdIns(4,5) P 2 responses in reperfusion. Thus preconditioning and α 1A -AR overexpression have different effects on early signalling responses, even though both prevented Ins(1,4,5) P 3 generation. These studies demonstrate a selective inhibitory action of heightened α 1A -AR activity on immediate post-receptor signalling responses in early post-ischaemic reperfusion.
Articles
Beth A. Beidleman, Stephen R. Muza, Charles S. Fulco, Allen Cymerman, Janet E. Staab, Michael N. Sawka, Steven F. Lewis, Gary S. Skrinar
Clin Sci (Lond) (2006) 111 (2): 163-169.
Published: 13 July 2006
... and during both exercise work bouts for measurements of WBC count, leucocyte subset counts, cortisol, adrenaline (epinephrine) and noradrenaline (norepinephrine). WBC, neutrophil and lymphocyte counts increased significantly ( P <0.05) during rest and exercise from SL to PreIAE and decreased ( P...
Abstract
Recent studies have demonstrated that brief daily IAE (intermittent altitude exposure) was equally as effective as continuous altitude residence in inducing physiological adaptations consistent with altitude acclimatization. Although the positive benefits of IAE have been clearly defined, the potential negative consequences of IAE on health, specifically the immune system, remain undefined. The present study determined the effects of IAE on WBC (white blood cell) and hormonal responses during rest and exercise at 4300 m altitude. Six lowlanders (age, 23±2 years; body weight, 77±6 kg; values are means±S.E.M.) completed a V ̇ O 2 max (maximal O 2 uptake) and submaximal cycle ergometer test during a 30-h SL (sea level) exposure and during a 30 h exposure to 4300 m altitude-equivalent once before (PreIAE) and once after (PostIAE) a 3-week period of IAE (4 h·day −1 , 5 days·week −1 , 4300 m). The submaximal cycle ergometer test consisted of two consecutive 15-min work bouts at 40% and 70% of altitude-specific V ̇ O 2 max. Blood samples were obtained at rest and during both exercise work bouts for measurements of WBC count, leucocyte subset counts, cortisol, adrenaline (epinephrine) and noradrenaline (norepinephrine). WBC, neutrophil and lymphocyte counts increased significantly ( P <0.05) during rest and exercise from SL to PreIAE and decreased ( P <0.05) during rest and exercise from PreIAE to PostIAE. Monocyte counts decreased ( P <0.05) during rest and exercise from PreIAE to PostIAE, but eosinophil and basophil counts did not change. Cortisol, adrenaline and noradrenaline did not change during rest or exercise from SL to PreIAE or PostIAE, but all increased significantly ( P <0.05) from rest during the two work bouts. In conclusion, this type of IAE stimulus did not induce a hormonal stress response and did no harm in terms of activation of the immune system at altitude, as measured by WBC and leucocyte subset counts. This method of pre-acclimatization can therefore be highly recommended for inducing altitude acclimatization without the ‘altitude residency’ requirement.
Articles
Reza Mobini, Michael Fu, Per-Anders Jansson, Claes-Håkan Bergh, Margareta Scharin Täng, Finn Waagstein, Bert Andersson
Clin Sci (Lond) (2006) 110 (3): 329-336.
Published: 10 February 2006
... present study, we studied the acute effects of the imidazoline-receptor agonist moxonidine on haemodynamics, NA (noradrenaline) kinetics and myocardial metabolism. Fifteen patients with CHF (chronic heart failure) were randomized to a single dose of 0.6 mg of sustained-release moxonidine or matching...
Abstract
Although β-adrenergic blockade is beneficial in heart failure, inhibition of central sympathetic outflow using moxonidine has been associated with increased mortality. In the present study, we studied the acute effects of the imidazoline-receptor agonist moxonidine on haemodynamics, NA (noradrenaline) kinetics and myocardial metabolism. Fifteen patients with CHF (chronic heart failure) were randomized to a single dose of 0.6 mg of sustained-release moxonidine or matching placebo. Haemodynamics, NA kinetics and myocardial metabolism were studied over a 2.5 h time period. There was a significant reduction in pulmonary and systemic arterial pressures, together with a decrease in cardiac index in the moxonidine group. Furthermore, there was a simultaneous reduction in systemic and cardiac net spillover of NA in the moxonidine group. Analysis of myocardial consumption of substrates in the moxonidine group showed a significant increase in non-esterified fatty acid consumption and a possible trend towards an increase in myocardial oxygen consumption compared with the placebo group ( P =0.16). We conclude that a single dose of moxonidine (0.6 mg) in patients already treated with a β-blocker reduced cardiac and overall sympathetic activity. The finding of increased lipid consumption without decreased myocardial oxygen consumption indicates a lack of positive effects on myocardial metabolism under these conditions. We suggest this might be a reason for the failure of moxonidine to prevent deaths in long-term studies in CHF.
Articles
Jean-Pierre Wolf, Malika Bouhaddi, Francis Louisy, Andrei Mikehiev, Laurent Mourot, Sylvie Cappelle, Fabrice Vuillier, Pierre Andre, Lucien Rumbach, Jacques Regnard
Clin Sci (Lond) (2006) 110 (3): 369-377.
Published: 10 February 2006
... patients with Parkinson's disease (PD) with Hoehn and Yahr stages 1–4. Patients were investigated once with their regular treatment and once after 12 h of interruption of L -dopa treatment. L -Dopa intake significantly reduced systolic and diastolic blood pressure, heart rate and plasma noradrenaline and...
Abstract
In the present study, the effects of L -dopa treatment on cardiovascular variables and peripheral venous tone were assessed in 13 patients with Parkinson's disease (PD) with Hoehn and Yahr stages 1–4. Patients were investigated once with their regular treatment and once after 12 h of interruption of L -dopa treatment. L -Dopa intake significantly reduced systolic and diastolic blood pressure, heart rate and plasma noradrenaline and adrenaline in both the supine and upright (60°) positions. A significant reduction in stroke volume and cardiac output was also seen with L -dopa. The vascular status of the legs was assessed through thigh compression during leg weighing, a new technique developed in our laboratory. Healthy subjects were used to demonstrate that this technique provided reproducible results, consistent with those provided by strain gauge plethysmography of the calf. When using this technique in patients with PD, L -dopa caused a significant lowering of vascular tone in the lower limbs as shown, in particular, by an increase in venous distensibility. Combined with the results of the orthostatic tilting, these findings support that the treatment-linked lowering of plasma noradrenaline in patients with PD was concomitant with a significant reduction in blood pressure, heart rate and vascular tone in the lower limbs. These pharmacological side-effects contributed to reduce venous return and arterial blood pressure which, together with a lowered heart rate, worsened the haemodynamic status.
Articles
Clin Sci (Lond) (2005) 109 (5): 431-437.
Published: 24 October 2005
... present in the brain, kidney, heart and vasculature. However, each differentially influences blood pressure and sympathetic transmission. Activation of α 2A -ARs in cardiovascular control centres of the brain lowers blood pressure and decreases plasma noradrenaline (norepinephrine), activation of...
Abstract
Cardiovascular regulation by the sympathetic nervous system is mediated by activation of one or more of the nine known subtypes of the adrenergic receptor family; α 1A -, α 1B -, α 1D -, α 2A -, α 2B -, α 2C -, β 1 -, β 2 - and β 3 -ARs (adrenoceptors). The role of the α 2 -AR family has long been known to include presynaptic inhibition of neurotransmitter release, diminished sympathetic efferent traffic, vasodilation and vasoconstriction. This complex response is mediated by one of three subtypes which all uniquely affect blood pressure and blood flow. All three subtypes are present in the brain, kidney, heart and vasculature. However, each differentially influences blood pressure and sympathetic transmission. Activation of α 2A -ARs in cardiovascular control centres of the brain lowers blood pressure and decreases plasma noradrenaline (norepinephrine), activation of peripheral α 2B -ARs causes sodium retention and vasoconstriction, whereas activation of peripheral α 2C -ARs causes cold-induced vasoconstriction. In addition, non-selective agonists elicit endothelium-dependent vasodilation and presynaptic inhibition of noradrenaline release. The evidence that each of these receptor subtypes uniquely participates in cardiovascular control is discussed in this review.
Articles
Tomi LAITINEN, Hanna HUOPIO, Ilkka VAUHKONEN, Cyril CAMARO, Juha HARTIKAINEN, Markku LAAKSO, Leo NISKANEN
Clin Sci (Lond) (2003) 105 (3): 315-322.
Published: 01 September 2003
... adrenaline concentration (from 0.19±0.03 to 1.68±0.32 nmol/l; P <0.001), and a modest 1.3-fold increase in the plasma noradrenaline concentration (from 1.74±0.22 to 2.02±0.19 nmol/l; P <0.05) compared with baseline. Furthermore, we observed significant decreases in diastolic blood pressure (from 68±3...
Abstract
The effects of hypoglycaemia during hyperinsulinaemia, occurring under various pathophysiological conditions, on the cardiovascular regulatory system and vasculature are largely unknown. The aim of the present study was to investigate regulatory and haemodynamic responses to acute hyperinsulinaemia and consequent hypoglycaemia in 18 healthy subjects. Blood sampling and 5 min ECG and blood pressure recordings were performed at baseline and during the euglycaemic and hypoglycaemic phases of a hyperinsulinaemic clamp. Heart rate variability (HRV) and blood pressure variability (BPV) were assessed by using power spectral analysis, and baroreflex sensitivity (BRS) was assessed using the cross-spectral method. Stroke volume was assessed from the non-invasive blood pressure signal by the arterial pulse contour method. Euglycaemic hyperinsulinaemia did not change plasma catecholamine concentrations, HRV, BPV, BRS, heart rate, blood pressure, stroke volume, cardiac output or peripheral resistance. However, hyperinsulinaemic hypoglycaemia resulted in an 11.7-fold increase in the plasma adrenaline concentration (from 0.19±0.03 to 1.68±0.32 nmol/l; P <0.001), and a modest 1.3-fold increase in the plasma noradrenaline concentration (from 1.74±0.22 to 2.02±0.19 nmol/l; P <0.05) compared with baseline. Furthermore, we observed significant decreases in diastolic blood pressure (from 68±3 to 60±3 mmHg; P <0.05) and peripheral resistance (from 24.1±1.2 to 18.5±1.1 mmHg·min -1 ·l -1 ; P <0.01). Stroke volume and cardiac output increased markedly from the euglycaemic to the hypoglycaemic period only ( P <0.01 for both). Hypoglycaemia did not influence HRV, BPV or BRS. Our findings indicate that hyperinsulinaemic hypoglycaemia is characterized by a significant increase in the plasma adrenaline concentration and by decreases in peripheral resistance and blood pressure. Counter-regulation during hyperinsulinaemic hypoglycaemia involves selective adrenomedullary sympathetic activation, and does not influence cardiac parasympathetic regulation or baroreflex control of heart rate.
Articles
Clin Sci (Lond) (2003) 104 (6): 649-654.
Published: 01 June 2003
...David S. GOLDSTEIN; Courtney HOLMES; Nicholas PATRONAS; Irwin J. KOPIN In multiple system atrophy (MSA) and pure autonomic failure (PAF), orthostatic hypotension (OH) results from deficient noradrenaline release from sympathetic nerves during standing. Post-mortem findings have indicated loss of...
Abstract
In multiple system atrophy (MSA) and pure autonomic failure (PAF), orthostatic hypotension (OH) results from deficient noradrenaline release from sympathetic nerves during standing. Post-mortem findings have indicated loss of central noradrenergic cells in both diseases. The present study sought in vivo neurochemical evidence for central noradrenergic deficiency in patients with OH due to MSA or PAF. A total of 28 patients with OH (18 with MSA; 10 with PAF) had cerebrospinal fluid and blood sampled for levels of noradrenaline and its neuronal metabolite dihydroxyphenylglycol. A control group of 44 subjects included 10 elderly normal volunteers, 10 patients with Alzheimer's disease, 18 patients with dysautonomia (postural tachycardia syndrome or neurocardiogenic syncope) and six patients with MSA in the absence of OH. Patients with OH had lower cerebrospinal fluid concentrations of noradrenaline (0.53±0.07 nmol/l) and dihydroxyphenylglycol (6.52±0.46 nmol/l) than did control subjects (0.90±0.09 and 9.64±0.46 nmol/l respectively; P =0.0001). The MSA + OH group had higher plasma levels of both catechols (noradrenaline, 1.31±0.16 nmol/l; dihydroxyphenylglycol, 5.08±0.43 nmol/l) than did the PAF group (noradrenaline, 0.38±0.08 nmol/l; dihydroxyphenylglycol, 2.53±0.30 nmol/l; P <0.001), despite similarly low cerebrospinal fluid levels. Among MSA patients, those with OH had lower cerebrospinal fluid levels of noradrenaline and dihydroxyphenylglycol than those without OH (noradrenaline, 1.71±0.64 nmol/l; dihydroxyphenylglycol, 10.41±1.77 nmol/l respectively; P =0.006). The findings are consistent with central noradrenergic deficiency in both MSA + OH and PAF. In MSA, central noradrenergic deficiency seems to relate specifically to OH.
Articles
Maria G. MELIS, Giannina SECCHI, Patrizia BRIZZI, Cristiana SEVERINO, Mario MAIOLI, Giancarlo TONOLO
Clin Sci (Lond) (2002) 103 (4): 397-402.
Published: 05 September 2002
... during the exogenous infusion of noradrenaline. We studied groups of non-diabetic normotensive subjects: eight with the wild-type Trp64Trp β 3 AR and eight with the Trp64Arg variant. The subjects each received, on two different days (randomized, double-blind fashion), a 4h infusion of either...
Abstract
The β 3 -adrenergic receptor (β 3 AR) plays a critical role in lipid metabolism, and thus alterations in its function may be involved in the metabolic syndrome. Indeed, we have found previously that the Trp64Arg amino acid variant of the β 3 AR is associated with hypertension and higher serum triacylglycerol levels in the Sardinian population. The aim of the present study was to evaluate the effect of the Trp64Arg β 3 AR variant on the regulation of triacylglycerol levels and blood pressure during the exogenous infusion of noradrenaline. We studied groups of non-diabetic normotensive subjects: eight with the wild-type Trp64Trp β 3 AR and eight with the Trp64Arg variant. The subjects each received, on two different days (randomized, double-blind fashion), a 4h infusion of either noradrenaline (0.147nmol·min -1 ·kg -1 ) or Emagel (subjects had fasted for at least 12h). The only available subject with a homozygous mutant Arg64Arg β 3 AR was also studied. Blood pressure was measured every 10min using a sphygmomanometer, and blood samples were taken every 30min from the contralateral vein for biochemical determinations. After a 4h noradrenaline infusion, significant increases in diastolic blood pressure (from 83±2 to 91±3mmHg; P <0.01) and serum triacylglycerol levels (from 1.69±0.4 to 1.79±0.6mmol/l; P <0.05) were observed compared with basal values in subjects with the Trp64Arg β 3 AR variant, whereas subjects with the Trp64Trp β 3 AR did not show any significant change over the infusion period. Glycaemia had increased significantly only at the end of the first 1h of infusion in subjects with the Trp64Arg variant (from 5.0±0.1 to 5.8±0.3mmol/l; P <0.05), with no significantly different behaviour compared with those subjects with the Trp64Trp β 3 AR during the remaining infusion period. The effects of noradrenaline infusion were more marked in the subject with the Arg64Arg variant. In conclusion, our data indicate that the Trp64Arg amino acid variant of the β 3 AR confers increased sensitivity to the pressure effect of noradrenaline. Moreover, this variant also influences blood triacylglycerol levels and, to a degree, glucose metabolism.
Articles
Clin Sci (Lond) (2002) 102 (6): 661-666.
Published: 14 May 2002
... antagonist of ET-1 has not been evaluated in the forearm. The present study investigated the effects of BQ-123 on changes in FBF in response to ET-1 and noradrenaline (NA; norepinephrine), taking into account the possible influence of vasodilator effects of BQ-123 on responses to vasoconstrictors. Six...
Abstract
Endothelin-1 (ET-1) has been proposed to contribute to the regulation of vascular tone in humans. BQ-123, an ET A receptor antagonist, has also been reported to increase forearm blood flow (FBF) in vivo ; however, the efficacy of BQ-123 as an antagonist of ET-1 has not been evaluated in the forearm. The present study investigated the effects of BQ-123 on changes in FBF in response to ET-1 and noradrenaline (NA; norepinephrine), taking into account the possible influence of vasodilator effects of BQ-123 on responses to vasoconstrictors. Six subjects (age 25-34 years) participated in a double-blind randomized study. FBF was measured by forearm occlusion plethysmography. Drugs were infused intra-arterially into the non-dominant arm (study arm) on four separate occasions; the non-infused arm was used as a control. The effects of BQ-123 (50nmol/min for 60min, or 300nmol/min for 5min followed by saline for 55min) were compared with the effects of infusion of sodium nitroprusside (SNP; 12nmol/min for 60min) or saline on vasoconstriction induced by ET-1 (10pmol/min for 7min) and NA (120pmol/min for 7min). Infusion of BQ-123 at either dose did not significantly increase FBF, whereas SNP increased FBF by 134% ( P = 0.03). ET-1 significantly reduced FBF, and this effect was almost completely inhibited by both doses of BQ-123, but was unaffected by SNP. NA also reduced FBF, and this action was unaffected by BQ-123 or SNP. The data show that BQ-123 is a selective ET-1 antagonist, but do not confirm a major role for ET-1 in influencing resting forearm vascular tone in young normotensive subjects.
Articles
Clin Sci (Lond) (2001) 101 (4): 377-383.
Published: 14 September 2001
... before the first exercise session. Compared with sea level, hypoxia progressively decreased the maximal heart rate from day 1 and onwards; also, hypoxia by itself increased plasma noradrenaline levels after maximal exercise. Domperidone further increased maximal noradrenaline concentrations, but had no...
Abstract
This study examined the effects of dopamine D 2 -receptor blockade on the early decrease in maximal heart rate at high altitude (4559m). We also attempted to clarify the time-dependent component of this reduction and the extent to which it is reversed by oxygen breathing. Twelve subjects performed two consecutive maximal exercise tests, without and with oxygen supplementation respectively, at sea level and after 1, 3 and 5 days at altitude. On each study day, domperidone (30mg; n = 6) or no medication ( n = 6) was given 1h before the first exercise session. Compared with sea level, hypoxia progressively decreased the maximal heart rate from day 1 and onwards; also, hypoxia by itself increased plasma noradrenaline levels after maximal exercise. Domperidone further increased maximal noradrenaline concentrations, but had no effect on maximal heart rate. On each study day at altitude, oxygen breathing completely reversed the decrease in maximal heart rate to values not different from those at sea level. In conclusion, dopamine D 2 -receptor blockade with domperidone demonstrates that hypoxic exercise in humans activates D 2 -receptors, resulting in a decrease in circulating levels of noradrenaline. However, dopamine D 2 -receptors are not involved in the hypoxia-induced decrease in the maximal heart rate. These data suggest that receptor uncoupling, and not down-regulation, of cardiac adrenoreceptors, is responsible for the early decrease in heart rate at maximal hypoxic exercise.
Articles
Clin Sci (Lond) (2000) 99 (1): 57-63.
Published: 14 June 2000
... activity in CHF. Correspondence : Dr Bronwyn Kingwell (e-mail b.kingwell@alfred.org.au ). 19 10 1999 14 1 2000 16 3 2000 The Biochemical Society and the Medical Research Society © 2000 2000 acetylcholine heart failure nitric oxide noradrenaline oxygen 57Clinical...
Abstract
Despite providing symptomatic relief in patients with congestive heart failure (CHF), supplemental oxygen (O 2 ) has been demonstrated to increase total peripheral resistance. The present study investigated the possibility that O 2 inhalation reduces nitric oxide (NO) bioavailability, using endothelium-dependent (acetylcholine) and -independent (phentolamine) vasodilators, and the antioxidant ascorbic acid. Ten patients (nine male and one female) with primary left ventricular failure participated in the study. Forearm venous occlusion plethysmography was used to study blood flow responses to acetylcholine and the α-adrenergic antagonist phentolamine during inhalation of either room air or 100% O 2 , with and without the simultaneous infusion of ascorbic acid. Neither O 2 inhalation (3.9±0.4 compared with 3.8±0.3 ml⋅min -1 ⋅100 ml -1 ) nor ascorbic acid infusion (5.2±0.4 compared with 5.5±0.4 ml⋅min -1 ⋅100 ml -1 ) affected resting forearm blood flow. The percentage increase from basal blood flow after acetylcholine infusion was not altered by either O 2 inhalation or ascorbic acid infusion (room air, 140±55%; O 2 , 118±46%; ascorbic acid, 147±39%; ascorbic acid+O 2 , 109±31%). O 2 inhalation did, however, reduce the dilation induced by phentolamine (room air, 131±24%; O 2 , 80±14%; P < 0.05). These data indicate that oxygen inhalation does not increase forearm vascular resistance. Secondly, preservation of reactivity to acetylcholine during O 2 inhalation suggests that degradation of NO by O 2 -derived free radicals is not enhanced. Attenuation of phentolamine-induced vasodilation during O 2 inhalation, however, implies increased adrenergic activity, which may possibly exacerbate the detrimental effects of elevated sympathetic activity in CHF.
Articles
Clin Sci (Lond) (2000) 98 (2): 193-200.
Published: 11 January 2000
... effects with those of noradrenaline (NA; norepinephrine). All sheep were chronically instrumented. Six sheep received l -NMMA (7 mg·kg -1 ·h -1 ), six sheep received NA, and seven sheep received the carrier alone (0.9% NaCl). The NA dosage was continuously and individually adjusted to achieve the same...
Abstract
This prospective, non-randomized, controlled experimental study looks at the effects of N Ω -monomethyl- l -arginine ( l -NMMA) on haemodynamics, oxygen transport and regional blood flow in healthy and septic sheep, and compares these effects with those of noradrenaline (NA; norepinephrine). All sheep were chronically instrumented. Six sheep received l -NMMA (7 mg·kg -1 ·h -1 ), six sheep received NA, and seven sheep received the carrier alone (0.9% NaCl). The NA dosage was continuously and individually adjusted to achieve the same increase in blood pressure as observed in matched sheep of the l -NMMA group (non-septic phase). Treatment was discontinued after 3 h. Sepsis was initiated and maintained by a continuous infusion of live Pseudomonas aeruginosa . After 24 h of sepsis, the sheep were again challenged over a treatment period of 3 h with their previously assigned drug (septic phase). During the non-septic phase of the experiment, NA and l -NMMA both caused an increase in mean arterial pressure (MAP) through vasoconstriction. Ater 24 h of sepsis, all sheep developed a hyperdynamic circulatory state. While l -NMMA caused an increase in MAP through intense vasoconstriction, NA caused MAP to increase through a further elevation of the cardiac index. The NA dosage needed was significantly higher in the septic phase compared with the non-septic phase, reflecting a reduced vascular responsiveness to catecholamines during sepsis. Renal blood flow remained unchanged during either treatment in both the non-septic and the septic phases. Nevertheless, urine output increased during NA treatment in both the non-septic and the septic phases, while l -NMMA caused urine output to increase only under septic conditions.
Articles
Clin Sci (Lond) (1999) 97 (6): 639-647.
Published: 29 October 1999
... in normal renal interlobular and subcutaneous vessels from uraemic patients. In human subcutaneous arteries from uraemic subjects, noradrenaline- and KCl-induced vasoconstrictions were enhanced when nitric oxide (NO) production was blocked with N G -nitro- L -arginine methyl ester ( L -NAME), but...
Abstract
This study investigated potential reasons why erythropoietin (EPO) given therapeutically to patients with renal failure may increase peripheral, but not renal, vascular resistance. This was done by comparing the effects of EPO on resting tension in normal renal interlobular and subcutaneous vessels from uraemic patients. In human subcutaneous arteries from uraemic subjects, noradrenaline- and KCl-induced vasoconstrictions were enhanced when nitric oxide (NO) production was blocked with N G -nitro- L -arginine methyl ester ( L -NAME), but were unaffected by EPO, while acetylcholine- and bradykinin-induced concentration-dependent relaxations were markedly attenuated by L -NAME, but not by EPO. The noradrenaline- and KCl-induced vasoconstrictions of human renal interlobular arteries were unaffected by the presence of L -NAME, but were attenuated by EPO (20 units·ml -1 ) by some 33% ( P < 0.01); this effect was enhanced by the co-administration of L -NAME. Acetylcholine and bradykinin caused comparable dilatations of the interlobular arteries; the response to the former was attenuated by L -NAME, but none of these responses were changed by EPO. EPO given alone, at a concentration of either 0.1 or 20 units·ml -1 , had no effect on basal resting tone. NO production mediated both acetylcholine- and bradykinin-induced relaxation in this vessel type. In contrast, in the interlobular arteries there was no indication of NO modulating the level of vasoconstriction, and it only mediated acetylcholine-induced dilation. These acute responses to EPO only partially explain its differential effects on the vasculature in renal failure.
Articles
Clin Sci (Lond) (1999) 97 (5): 539-546.
Published: 17 September 1999
...-arterial cannulation in either the dominant or the non-dominant forearm. Cannulation of a forearm brachial artery has a small effect on baseline blood flow. Responses to intra-arterially infused noradrenaline (norepinephrine) were not influenced by left or right arm dominance. Intravenous infusion of...
Abstract
The human forearm model is used extensively in physiological, pharmacological and clinical investigations. Effects of arm dominance or arterial cannulation on forearm flow measurements have never been tested formally. In the present study we tested the hypotheses that left or right arm dominance or cannulation of the brachial artery do not affect forearm haemodynamic responses to physiological or pharmacological stimuli. Results obtained in 16 volunteers showed that forearm blood flow responses to physiological stimuli are comparable before and after intra-arterial cannulation in either the dominant or the non-dominant forearm. Cannulation of a forearm brachial artery has a small effect on baseline blood flow. Responses to intra-arterially infused noradrenaline (norepinephrine) were not influenced by left or right arm dominance. Intravenous infusion of noradrenaline in eight subjects resulted in small responses in forearm blood flow that were slightly asymmetrical. During the intravenous infusion of noradrenaline, forearm blood flow or the forearm blood flow ratio did not reflect the marked increase in FVR that occurred. These results support our hypotheses (a) that either arm can be used as the control or intervention arm, and (b) that intra-arterial cannulation does not affect the results of intra-arterial infusion studies.
Articles
Barry J. KNEALE, Philip J. CHOWIENCZYK, Sally E. BRETT, JohnR. COCKCROFT, James M. RITTER, James M. RITTER
Clin Sci (Lond) (1999) 97 (3): 277-282.
Published: 15 July 1999
...; an inhibitor of NO biosynthesis), relative to the response to noradrenaline, has been reported in hypertensive patients and interpreted as evidence of reduced basal NO biosynthesis. We sought to determine whether reduced sensitivity of forearm vasculature to the vasoconstrictor action of l -NMMA...
Abstract
A role for abnormal NO production in essential hypertension remains controversial. Blunted vasoconstriction of forearm resistance vasculature in response to N G -monomethyl-⌊-arginine (⌊-NMMA; an inhibitor of NO biosynthesis), relative to the response to noradrenaline, has been reported in hypertensive patients and interpreted as evidence of reduced basal NO biosynthesis. We sought to determine whether reduced sensitivity of forearm vasculature to the vasoconstrictor action of l -NMMA relative to that of noradrenaline is a consistent finding in essential hypertension. We studied a group of patients ( n = 32; blood pressure 176±4/102±2 mmHg; means±S.E.M.) and a group of healthy normotensive controls ( n = 32; blood pressure 130±2/75±1 mmHg). Noradrenaline (60–240 pmol·min -1 ) and ⌊-NMMA (1–4 μ mol·min -1 ) were infused into the brachial artery, and forearm blood flow was measured by venous occlusion plethysmography. The effects of each vasoconstrictor were similar in hypertensive and control subjects. The highest dose of l -NMMA reduced forearm blood flow by 0.75±0.12 ml·min -1 ·dl -1 in the control group and by 0.89±0.10 ml·min -1 ·dl -1 in the hypertensive group. The study had 90% power (with P = 0.05) to detect a 10% difference in forearm blood flow response between the hypertensive and control groups. We conclude that reduced sensitivity of forearm resistance vasculature to the vasoconstrictor action of l -NMMA is not a universal feature of essential hypertension. This argues against a primary role for reduced basal NO biosynthesis in skeletal muscle resistance vessels in the pathogenesis of essential hypertension.
Articles
Djillali ANNANE, Véronique BAUDRIE, Anne-Sophie BLANC, Dominique LAUDE, Jean-Claude RAPHAËL, Jean-Luc ELGHOZI
Clin Sci (Lond) (1999) 96 (6): 613-621.
Published: 11 May 1999
... healthy subjects), but the acceleratory response to atropine, or to 60 ° head-up tilt, was maintained. Resting plasma noradrenaline levels were high in acute GBS, but the secretory response to tilt was preserved. Desensitization to noradrenaline was observed in acute GBS with a reduced pressor action of...
Abstract
The effect of Guillain-Barré syndrome (GBS) on the short-term variability of blood pressure and heart rate was evaluated in six patients presenting with a moderate form of the syndrome, i.e. unable to stand up unaided and without respiratory failure, at the height of the disease and during recovery. The patients were compared with six age-matched healthy volunteers. During the acute phase of the syndrome, GBS patients exhibited a significant heart rate elevation (+26 beats/min compared with healthy subjects), but the acceleratory response to atropine, or to 60 ° head-up tilt, was maintained. Resting plasma noradrenaline levels were high in acute GBS, but the secretory response to tilt was preserved. Desensitization to noradrenaline was observed in acute GBS with a reduced pressor action of this α-adrenoceptor agonist. Blood pressure levels were normal and head-up tilt did not induce orthostatic hypotension in this moderate form of GBS. Power spectral analysis demonstrated marked alterations in cardiovascular variability. The overall heart period variability was markedly reduced with the reduction predominantly in the high-frequency (respiratory) range (-73%). The low-frequency component of heart period variability was also reduced (-54%). This cardiovascular profile of moderate GBS at the height of the disease could result from a demyelination of the reflex loop controlling respiratory oscillations in heart rate and from a desensitization of the arterial tree to an elevated plasma noradrenaline. Sympathetic nervous activation may contribute to the high resting heart rate in acute GBS.
Articles
Clin Sci (Lond) (1999) 96 (6): 589-595.
Published: 07 May 1999
... and the Medical Research Society © 1999 1999 adrenaline catecholamines cortisol glucose infarct size myocardial infarction noradrenaline unstable angina 589Clinical Science (1999) 96, 589ñ595 (Printed in Great Britain) Circulating stress hormone and insulin concentrations in acute...
Abstract
We re-examined, in the context of modern practice, plasma insulin and stress hormone concentrations in patients admitted to hospital with acute coronary syndromes. Venous blood sampling was carried out prior to anti-thrombotic therapy in 148 patients with myocardial infarction (MI); 76 patients with unstable angina (UA) pectoris were also studied, together with 27 patients with non-cardiac chest pain (NCP). There were significant progressive increases in the concentrations of catecholamines, cortisol, glucose and insulin from NCP to UA to MI patients. Hyperglycaemia (glucose > 8 mmol/l) was present in over 50% of MI patients. The plasma cortisol and insulin levels were both significantly positively correlated with the glucose concentration on admission. Only the cortisol concentration was correlated with peak cardiac enzyme levels. The glucose and insulin concentrations on admission in 141 MI and UA patients were related to insulin resistance, as judged from subsequent insulin and glucose concentrations measured while fasting and during a glucose tolerance test. The product of admission insulin×glucose (divided by 25; the admission insulin-resistance index, or AIRI) was significantly correlated with indices of insulin resistance, and was significantly higher (approximately double) in the MI group (7.81±0.76) and the UA group (6.88±1.19) than in the control NCP group (3.59±0.06; Kuskul–Wallis: P = 0.0001), implying that the insulin levels in the first two groups were approximately twice as high as is appropriate for the glucose levels. The ethnic origin of 20% of the patients was the Indian subcontinent; admission insulin and glucose levels in this subgroup were higher than in the non-Asians across all the groups with chest pain. Cortisol was the only stress hormone that was raised in proportion to the size of the infarct, and is a likely partial cause of the elevation in blood glucose. The high insulin levels were related to the prevalence of insulin resistance, and this was particularly important in the Asian subgroup presenting with MI and UA. Thus it appears feasible to identify acute coronary syndrome patients who are insulin-resistant at a time (on admission) when alternative early therapeutic strategies can be instituted.
Articles
John R. SHANNON, Keith GOTTESDIENER, Jens JORDAN, Kong CHEN, Stacey FLATTERY, Patrick J. LARSON, Mari Rios CANDELORE, Barry GERTZ, David ROBERTSON, Ming SUN
Clin Sci (Lond) (1999) 96 (5): 483-491.
Published: 14 April 1999
... -, β 2 - and β 3 -adrenoreceptors. Twenty-four-hour energy expenditure was 3.6% greater (8965±1301 versus 8648±1347 kJ, P < 0.05) with ephedrine than with placebo, but mechanical work was not different between the ephedrine and placebo periods. Noradrenaline excretion was lower with ephedrine (0.032...
Abstract
Ephedrine is used to help achieve weight control. Data on its true efficacy and mechanisms in altering energy balance in human subjects are limited. We aimed to determine the acute effect of ephedrine on 24-h energy expenditure, mechanical work and urinary catecholamines in a double-blind, randomized, placebo-controlled, two-period crossover study. Ten healthy volunteers were given ephedrine (50 mg) or placebo thrice daily during each of two 24-h periods (ephedrine and placebo) in a whole-room indirect calorimeter, which accurately measures minute-by-minute energy expenditure and mechanical work. Measurements were taken of 24-h energy expenditure, mechanical work, urinary catecholamines and binding of (±)ephedrine in vitro to human β 1 -, β 2 - and β 3 -adrenoreceptors. Twenty-four-hour energy expenditure was 3.6% greater (8965±1301 versus 8648±1347 kJ, P < 0.05) with ephedrine than with placebo, but mechanical work was not different between the ephedrine and placebo periods. Noradrenaline excretion was lower with ephedrine (0.032±0.011 μ g/mg creatinine) compared with placebo (0.044±0.012 μ g/mg creatinine) ( P < 0.05). (±)Ephedrine is a relatively weak partial agonist of human β 1 - and β 2 -adrenoreceptors, and had no detectable activity at human β 3 -adrenoreceptors. Ephedrine (50 mg thrice daily) modestly increases energy expenditure in normal human subjects. A lack of binding of ephedrine to β 3 -adrenoreceptors and the observed decrease in urinary noradrenaline during ephedrine treatment suggest that the thermogenic effect of ephedrine results from direct β 1 -/β 2 -adrenoreceptor agonism. An indirect β 3 -adrenergic effect through the release of noradrenaline seems unlikely as urinary noradrenaline decreased significantly with ephedrine.
Articles
Gavin W. LAMBERT, Mario VAZ, Helen S. COX, Andrea G. TURNER, David M. KAYE, Garry L. JENNINGS, Murray D. ESLER
Clin Sci (Lond) (1999) 96 (2): 191-197.
Published: 01 February 1999
... neurotransmitter stemming from the brain. By combining this technique with a noradrenaline and adrenaline isotope dilution method for examining neuronal transmitter release, we were able to examine the association between central nervous system neurotransmitters and efferent sympathetic nervous outflow and...
Abstract
The afferent signals that evoke changes in energy intake with regard to body weight regulation are presumed to arise partly from body stores, with the most likely candidate being adipose tissue depots. However, clinical investigation of the neuronal circuitry involved in the central nervous system's processing of such satiety signals remains largely unexplored. Using percutaneously placed catheters in either the right or left internal jugular veins, we were able to quantify the release of central nervous system monoamine and indoleamine neurotransmitters in 64 weight-stable male subjects with varying degrees of adiposity. Veno-arterial plasma concentration differences and internal jugular blood or plasma flow were used, according to the Fick Principle, to quantify the amount of neurotransmitter stemming from the brain. By combining this technique with a noradrenaline and adrenaline isotope dilution method for examining neuronal transmitter release, we were able to examine the association between central nervous system neurotransmitters and efferent sympathetic nervous outflow and adrenomedullary function in human obesity. We found that brain 5-hydroxytryptamine (serotonin) turnover is chronically elevated in proportion to adiposity and is increased postprandially to a similar degree in lean and obese individuals. There was no difference in the degree of sympathetic nervous activity or rate of adrenaline secretion in the subjects examined. It therefore seems that in human obesity, in the face of a chronic elevation in peripheral satiety signals, brain serotonergic processes are switched on accordingly, but the subsequent physiological response involving a reduction in food intake, increased thermogenesis and sympathetic activity is in some way impeded.
Articles
Clin Sci (Lond) (1998) 96 (1): 41-47.
Published: 01 January 1999
... operated. In rat aorta, there was no significant difference between portal hypertensive and sham-operated animals in the contractile potency of KCl, noradrenaline or phenylephrine. In aortas from Wistar rats, the maximum response to KCl (0.71±0.12 ;g) and noradrenaline (1.00±0.17 ;g) but not phenylephrine...
Abstract
We have examined the effects of pre-hepatic portal hypertension on the responsiveness of aorta from Wistar and Sprague–Dawley rats. Rats were made portal hypertensive by creating a calibrated portal vein stenosis, or sham operated. In rat aorta, there was no significant difference between portal hypertensive and sham-operated animals in the contractile potency of KCl, noradrenaline or phenylephrine. In aortas from Wistar rats, the maximum response to KCl (0.71±0.12 ;g) and noradrenaline (1.00±0.17 ;g) but not phenylephrine (0.86±0.10 ;g) in portal hypertensive animals was significantly increased compared with that in sham-operated animals (0.45±0.04 ;g, 0.57±0.07 ;g, 0.71±0.05 ;g respectively). In aortas from Sprague–Dawley rats, the maximum response to KCl (1.21±0.21 ;g) and phenylephrine (1.54±0.30 ;g) but not noradrenaline (0.93±0.09 ;g) in portal hypertensive animals was significantly increased compared with that in sham-operated animals (0.59±0.09 ;g, 0.76±0.11 ;g, 1.04±0.10 ;g respectively). There was no difference between portal hypertensive and sham-operated Wistar rats in the affinity or maximum number of binding sites for [ 3 H]prazosin to α 1 -adrenoceptors in cardiac ventricular membranes. It is concluded that portal hypertension tends to produce an increase rather than a decrease in the contractile response to vasoconstrictors in aorta from both Wistar and Sprague–Dawley rats. This suggests that the diminished responsiveness to vasoconstrictors reported in portal hypertensive rats in vivo is not due to a diminished responsiveness at the level of the vascular smooth muscle.
Articles
Clin Sci (Lond) (1998) 95 (1): 59-66.
Published: 01 July 1998
... calorimetry and sympathetic nervous system activity from noradrenaline kinetics using [ 3 H]noradrenaline in 12 older men (70±4 years) and 12 older women (66±4 years) at rest and during 30 min of submaximal exercise (45% of peak oxygen consumption). 3. At rest, men oxidized more fat than women on both an...
Abstract
1. Gender differences in fat oxidation at rest and during exercise may contribute to higher body fat in women. We examined gender differences in fat oxidation at rest and during submaximal exercise and their relationship to sympathetic nervous system activity, free fatty acid availability, body composition and aerobic capacity in older volunteers. 2. We measured free fatty acid kinetics using [ 14 C]palmitate, absolute ( μ mol/min) and relative (respiratory quotient) rates of fat oxidation by indirect calorimetry and sympathetic nervous system activity from noradrenaline kinetics using [ 3 H]noradrenaline in 12 older men (70±4 years) and 12 older women (66±4 years) at rest and during 30 min of submaximal exercise (45% of peak oxygen consumption). 3. At rest, men oxidized more fat than women on both an absolute (88±19 versus 51±15 μ mol/min; P < 0.01) and relative (respiratory quotient: 0.80±0.04 versus 0.85±0.04; P < 0.01) basis. These differences were not related to noradrenaline appearance rate, free fatty acid concentration, body composition or aerobic capacity. During exercise, fat oxidation was higher ( P < 0.05 to P < 0.01) in men on an absolute level, but respiratory quotient did not differ. Higher absolute fat oxidation in men during exercise was explained by their higher absolute workload. Plasma free fatty acids and free fatty acid rate of appearance did not differ between men and women during exercise despite higher ( P < 0.05 to P < 0.01) plasma noradrenaline concentrations in men. 4. We conclude that: (i) resting fat oxidation is higher in older men compared with older women independent of differences in noradrenaline appearance rate, free fatty acid availability, body composition or aerobic capacity, and (ii) despite higher plasma noradrenaline concentrations during submaximal exercise, no gender differences in free fatty acid appearance rate or fat oxidation were found. These results suggest a sex dimorphism in post-absorptive fat metabolism in the elderly.
Articles
Clin Sci (Lond) (1998) 94 (6): 601-607.
Published: 01 June 1998
... nitroprusside (5 and 10 μg/min), before and after 1 h of sustained hypertension, induced by noradrenaline given intravenously. Identical measurements were made in 11 subjects before and during concomitant local intra-arterial infusion of noradrenaline without change in blood pressure and eight subjects were...
Abstract
1. Previous investigations have demonstrated an impaired endothelium-dependent vasodilatation (EDV) in patients with hypertension. The present study aimed to investigate if an acute rise in blood pressure to hypertensive levels impairs EDV in otherwise normotensive subjects. 2. Twenty-seven young, healthy, normotensive subjects were studied. Eight of these underwent evaluation of EDV and endothelium-independent vasodilatation (EIDV) by means of forearm blood flow measurements during local intra-arterial infusions of methacholine (2 and 4 μg/min) and sodium nitroprusside (5 and 10 μg/min), before and after 1 h of sustained hypertension, induced by noradrenaline given intravenously. Identical measurements were made in 11 subjects before and during concomitant local intra-arterial infusion of noradrenaline without change in blood pressure and eight subjects were studied during saline infusions. 3. One hour of sustained hypertension (diastolic blood pressure > 95 mmHg) significantly attenuated both forearm blood flow (17.4 ± 6.8 versus 27.4 ± 6.8 ml · min −1 · 100 ml −1 tissue at baseline, P < 0.05) and forearm vascular resistance decrease (3.2 ± 0.87 versus 7.4 ± 2.5 units at baseline, P < 0.05) during methacholine infusion. These attenuations were significantly more pronounced for methacholine than for sodium nitroprusside ( P < 0.05). In contrast, local intra-arterial noradrenaline infusions impaired vasodilatation induced by methacholine and sodium nitroprusside to a similar extent. Saline infusions did not change either EDV or EIDV. 4. Thus, an acute rise in blood pressure to hypertensive levels induced by noradrenaline impaired EDV more than EIDV in otherwise normotensive subjects, while no such selective effect of local noradrenaline was seen, suggesting that a high blood pressure impairs endothelial vasodilator function.
Articles
Clin Sci (Lond) (1998) 94 (6): 609-614.
Published: 01 June 1998
... the endogenous insulin response was inhibited with subcutaneous octreotide. 3. After placebo, hypertensive patients had slightly but significantly higher blood glucose levels than controls ( P < 0.0001), but comparable insulin concentrations ( P > 0.5). Plasma noradrenaline levels were...
Abstract
1. Hyperinsulinaemia and insulin resistance are thought to be intimately involved in the development of hypertension, but controversy remains as to whether hyperinsulinaemia is a consequence or a cause of hypertension per se , and whether it plays a role in the short-term regulation of blood pressure. 2. We studied six hypertensive patients [blood pressure 161(9)/101(2) mmHg] and seven normotensive control subjects [blood pressure 122(6)/76(4) mmHg], ( P < 0.005) using two oral glucose tolerance tests of 3 h duration. In one of these tests the endogenous insulin response was inhibited with subcutaneous octreotide. 3. After placebo, hypertensive patients had slightly but significantly higher blood glucose levels than controls ( P < 0.0001), but comparable insulin concentrations ( P > 0.5). Plasma noradrenaline levels were consistently lower in the hypertensive group ( P < 0.001). Blood pressure did not change in either group during the 3 h after glucose ingestion. 4. Octreotide completely abolished the immediate insulin response to glucose in all subjects (both P < 0.0001) and caused a delayed and significantly increased glycaemic response in born groups ( P < 0.0001). There were no significant differences in plasma glucose responses between groups; however, after octreotide, the hypertensive subjects had a greater insulin suppression than the controls ( P < 0.02). Octreotide suppressed noradrenaline levels in the normotensive group ( P < 0.001); they were also suppressed in the hypertensive group, but just failed to reach significance ( P = 0.056). Throughout the study the hypertensive group's noradrenaline levels remained generally lower than those in the control group ( P < 0.0001). 5. In this study there were no differences between hypertensive and normotensive subjects in fasting or post-glucose insulin levels, nor any significant change in blood pressure in either group when post-glucose hyperinsulinaemia was suppressed. This argues against insulin playing a direct role in the short-term regulation of blood pressure.
Articles
Mareomi Hamada, Yuji Shigematsu, Hideo Kawakami, Naoto Minamino, Kenji Kangawa, Hisayuki Matsuo, Kunio Hiwada
Clin Sci (Lond) (1998) 94 (1): 21-28.
Published: 01 January 1998
... antibody. Plasma levels of endothelin-1, atrial and brain natriuretic peptides and noradrenaline were also measured. 3. Plasma levels of adrenomedullin were higher in patients with hypertrophic cardiomyopathy (8.43 ± 3.73 pmol/l) than in normal controls (5.24 ± 0.44 pmol/l, P < 0.005). There was no...
Abstract
1. The aim of this study was to elucidate the pathophysiological role of adrenomedullin and the relation between adrenomedullin and other hormones in patients with hypertrophic cardiomyopathy. 2. Fourteen patients with hypertrophic obstructive cardiomyopathy (HOCM), 26 patients with hypertrophic non-obstructive cardiomyopathy (HNCM) and 14 normal control subjects participated in this study. Radioimmunoassay for plasma adrenomedullin concentration was performed with adrenomedullin-M antibody. Plasma levels of endothelin-1, atrial and brain natriuretic peptides and noradrenaline were also measured. 3. Plasma levels of adrenomedullin were higher in patients with hypertrophic cardiomyopathy (8.43 ± 3.73 pmol/l) than in normal controls (5.24 ± 0.44 pmol/l, P < 0.005). There was no significant difference between HOCM and HNCM patients. There was a weak correlation between plasma levels of adrenomedullin and total 12-lead QRS voltage in patients with hypertrophic cardiomyopathy ( r = 0323, P < 0.05) 4. Plasma levels of endothelin-1, atrial and brain natriuretic peptides were higher in hypertrophic cardiomyopathy than in normal controls. Endothelin-1 showed no significant difference between HOCM and HNCM patients, but atrial and brain natriuretic peptides were higher in HOCM than in HNCM patients. There was a positive correlation between plasma levels of adrenomedullin and endothelin-1 ( r = 0.575, P < 0.0001), but no correlation between plasma levels of adrenomedullin and atrial natriuretic peptide, brain natriuretic peptide and noradrenaline. 5. Our results indicate that adrenomedullin may play an important role to maintain haemodynamics in patients with hypertrophic cardiomyopathy, and its action may be related to endothelin-1 but independent of atrial natriuretic peptide, brain natriuretic peptide and noradrenaline.
Articles
Clin Sci (Lond) (1997) 93 (6): 519-525.
Published: 01 December 1997
... occlusion venous plethysmography combined with brachial artery infusions of the nitric oxide synthase inhibitor, N G -monomethyl-l-arginine (l-NMMA; 1, 2 and 4 μmol/min) with noradrenaline (60, 120 and 240 pmol/min) as a control vasoconstrictor. We also measured urinary nitrate excretion after a controlled...
Abstract
1. Basal release of nitric oxide from the vascular endothelium maintains a constant vasodilating tone. Impaired nitric oxide-mediated vasodilatation has been described in hypertension and atheromatous disease. Circulatory diseases account for considerable morbidity and almost half of all deaths in people over the age of 75 years. 2. We have therefore compared nitric oxide-dependent vasorelaxation in 12 healthy elderly subjects with 12 young volunteers matched for blood pressure, cholesterol and glucose, using forearm occlusion venous plethysmography combined with brachial artery infusions of the nitric oxide synthase inhibitor, N G -monomethyl-l-arginine (l-NMMA; 1, 2 and 4 μmol/min) with noradrenaline (60, 120 and 240 pmol/min) as a control vasoconstrictor. We also measured urinary nitrate excretion after a controlled 48 h low nitrate diet as an index of total body nitric oxide production and correlated these changes with forearm blood flow responses to l-NMMA and noradrenaline in both groups. 3. The mean age and blood pressure of the elderly subjects was 76 (range 66–82) years and 132/76 (SEM 4/3) mmHg respectively, while in the young these were 27 (20–35) years and 131/72 (4/3) mmHg respectively. l-NMMA and noradrenaline produced dose-dependent reductions in forearm blood flow in both groups. l-NMMA (4 μmol/min) produced less vasoconstriction in the elderly than in the young (−37.7 ± 2.6 versus −48.3 ± 4.2%; P = 0.017). The mean slope of the l-NMMA dose-response curves in the elderly was significantly less than the younger group (−35.2 ± 3.1 versus −63.7 ± 10.6; P = 0.041). Noradrenaline, 240 pmol/min, also produced less vasoconstriction in the elderly compared with the young (−22.8 ± 2.9 versus −35.3 ± 5.0%; P = 0.029) although the slopes of the dose—response curves did not differ significantly. 4. Urinary nitrate adjusted for creatinine clearance was also significantly higher in the younger group (460.6 ± 97.7 versus 205.9 ± 64.8 μmol/day; P = 0.042) and showed a significant correlation with the percentage change in forearm blood flow in response to the maximum dose of l-NMMA ( r = 0.5, P = 0.046). 5. We conclude that nitric oxide-mediated vasodilatation in the forearm vascular bed is diminished in old age and this reflects a more generalized reduction in nitric oxide production (as measured by urinary nitrate) in the circulation of older people. The blunted response to noradrenaline points to a more generalized reduction in vascular reactivity in the elderly.
Articles
Clin Sci (Lond) (1997) 93 (3): 227-234.
Published: 01 September 1997
...-arginine to adriamycin-pregnant rats or of N G -nitro-l-arginine-methyl ester (l-NAME) to normal pregnant rats. In other experiments, we assessed the response of isolated perfused arterial mesenteric vessels, precontracted with noradrenaline, to acetylcholine, l-arginine or l-NAME. 3. Blood pressure was...
Abstract
1. In previous studies we have shown that, after the administration of adriamycin, hypertension developed in rats who became pregnant (adriamycin-pregnant rats), whereas virgin animals remained normotensive. Subsequently, we showed that this hypertension was prevented by administration of l-arginine, suggesting that deficient synthesis of nitric oxide may be pathogenetic in this model. 2. To further assess the role of nitric oxide in this model, we measured mean arterial blood pressure after administration of l-arginine to adriamycin-pregnant rats or of N G -nitro-l-arginine-methyl ester (l-NAME) to normal pregnant rats. In other experiments, we assessed the response of isolated perfused arterial mesenteric vessels, precontracted with noradrenaline, to acetylcholine, l-arginine or l-NAME. 3. Blood pressure was decreased in normal pregnant rats, whereas it was elevated in adriamycin-pregnant rats. l-NAME treatment increased blood pressure in normal pregnant rats and l-arginine decreased it in adriamycin-pregnant rats. 4. Mesenteric vessels of adriamycin-pregnant rats exibited an exaggerated vasoconstrictory response to noradrenaline, when compared with the blunted response observed in normal pregnancy. The addition of l-NAME in vitro induced a further contraction, significantly greater in normal pregnant rats. The vasodilatory response to acetylcholine and l-arginine was greater in vessels from adriamycin-pregnant rats. In contrast, responses to either nitroprusside or diazoxide were similar in all groups. 5. The results suggest a state of reduced nitric oxide synthesis in rats with adriamycin nephropathy, leading to vascular maladaption and hypertension in pregnancy.
Articles
Clin Sci (Lond) (1997) 92 (4): 423-430.
Published: 01 April 1997
... Medical Research Society 1997 amino acid catecholamine dihydroxyphenylacetic acid 3,4-dihydroxyphenylalanine noradrenaline sympathetic activity Clinical Science (1997) 92,423-430 (Printed in Great Britain) 423 Effects of ordinary meals on plasma concentrations of 3,4=dihydroxyphenylalanine...
Abstract
1. Plasma concentrations of 3,4-dihydroxyphenylalanine (DOPA), dopamine sulphate (DA-S), and 3,4-dihydroxyphenylacetic acid (DOPAC) in humans have been claimed to be indexes of sympathetic nervous activity, but the source and significance of plasma DOPA, DOPAC and DA-S have not been completely elucidated. 2. The effects of ordinary meals on plasma concentrations of total dopamine, mainly DA-S, DOPAC and DOPA were studied in seven healthy subjects. Venous blood was collected every hour for 25 h, while subjects were either fasting or received three meals at 9.00 hours, 13.00 hours and 18.00 hours. Catecholamines and metabolites were determined by reverse-phase HPLC with electrochemical detection. Neutral amino acids were measured by ionexchange chromatography with photometric detection. 3. The food contained relatively little DOPA as compared with phenylalanine, tyrosine, isoleucine and tryptophan. The content of DA and DA-S varied considerably, with the greatest amount in the evening meal of open sandwiches. 4. Plasma DOPA decreased significantly after the meals at 13.00 hours and 18.00 hours, whereas concentrations of the other amino acids increased as expected. 5. Plasma DA-S increased significantly after meals and especially after the evening meal. Increments in DA-S above basal values after a meal were closely related to the content of DOPA+DA+DA-S in the meal. Plasma DOPAC increased significantly after the evening meal. 6. The decrease in plasma DOPA observed after a meal was probably due to uptake of DOPA by muscle tissue. Changes in plasma DA-S and DOPAC during this 25-h study reflected to a large extent the content of DOPA, DA and DA-S in the meals.
Articles
Clin Sci (Lond) (1997) 92 (3): 285-289.
Published: 01 March 1997
...Guido Grassi; Giambattista Bolla; Gino Seravalle; Carlo Turri; Antonio Lanfranchi; Giuseppe Mancia 1. Although plasma noradrenaline and muscle sympathetic nerve traffic have been shown to be suitable markers of sympathetic activity in man, no study has systematically compared the reproducibility...
Abstract
1. Although plasma noradrenaline and muscle sympathetic nerve traffic have been shown to be suitable markers of sympathetic activity in man, no study has systematically compared the reproducibility and sensitivity of these two indices of adrenergic tone. 2. Reproducibility data were collected in 10 subjects, in whom plasma noradrenaline was assessed by HPLC on blood samples withdrawn from an antecubital vein and efferent postganglionic muscle sympathetic nerve activity was measured by microneurography from a peroneal nerve, together with arterial blood pressure (Finapres technique). Measurements were obtained in a first session (session 1), 60 min later (session 2) and after 14 days (session 3). While muscle sympathetic nerve activity values recorded in the three different experimental sessions were closely and significantly correlated with each other ( r always >0.90, P < 0.001), noradrenaline showed a less significant correlation between sessions 1 and 2 ( r = 0.71, P < 0.05) or no correlation between sessions 1 and 3 ( r = 0.45, P not significant). 3. Sensitivity data were collected by evaluating muscle sympathetic nerve activity and noradrenaline values in three different age groups (young, middle-age and old subjects, n = 18), in three groups with different blood pressures (normotensive, mild and severe hypertensive subjects, n = 30) and in a group of eight subjects before and after a physical training programme, i.e. conditions known to increase or reduce sympathetic cardiovascular drive. Muscle sympathetic nerve activity was significantly increased by aging and hypertension, and reduced by physical training. The noradrenaline changes were much less marked and consistent. 4. These data suggest that muscle sympathetic nerve activity has a greater short- and medium-term reproducibility than noradrenaline. In several conditions known to modify sympathetic cardiovascular drive muscle sympathetic nerve activity also appears to change more clearly than noradrenaline.
Articles
Clin Sci (Lond) (1997) 92 (2): 133-138.
Published: 01 February 1997
... inhibitor, N G -monomethyl- l -arginine, and a control vasoconstrictor, noradrenaline. 2. Substance P and acetylcholine caused dose-dependent increases in forearm blood flow ( P < 0.001). When separated by 30 min saline infusions, repeated responses did not undergo tachyphylaxis. 3. Noradrenaline caused...
Abstract
1. Forearm blood flow responses to incremental challenges of acetylcholine and substance P, administered via the brachial artery, were measured by venous occlusion plethysmography in eight subjects in the presence of saline, the nitric oxide synthase inhibitor, N G -monomethyl- l -arginine, and a control vasoconstrictor, noradrenaline. 2. Substance P and acetylcholine caused dose-dependent increases in forearm blood flow ( P < 0.001). When separated by 30 min saline infusions, repeated responses did not undergo tachyphylaxis. 3. Noradrenaline caused a mean reduction in basal blood flow of 34–51% ( P < 0.001), and augmented the percentage increases in blood flow with both substance P ( P = 0.05) and acetylcholine ( P = 0.03) infusions. 4. N G -Monomethyl- l -arginine caused a mean reduction in basal blood flow of 42–45% ( P < 0.001) and significantly inhibited the responses to both substance P ( P < 0.001) and acetylcholine ( P = 0.05). 5. In comparison with saline responses, N G -monomethyl- l -arginine caused a mean inhibition of 69 ± 8% for substance P-induced vasodilatation and 40 ± 5% for acetylcholine-induced vasodilatation. However, comparing responses with those to the control vasoconstrictor noradrenaline, N G -monomethyl- l -arginine caused a mean inhibition of 81 ± 5% for substance P responses and 58 ± 3% for acetylcholine responses. Inhibition by N G -monomethyl- l -arginine of the response to substance P was significantly greater than inhibition of the response to acetylcholine ( P = 0.02). 6. Hence, in healthy men, a greater proportion of the forearm vasodilatation to substance P than to acetylcholine appears to be nitric oxide-mediated. Given its greater stability, substance P may be more suitable as a pharmacological tool in the investigation of stimulated nitric oxide production and endothelial cell function.
Articles
Clin Sci (Lond) (1996) 91 (5): 621-626.
Published: 01 November 1996
... subjects the proportion of natural killer cells was correlated with cAMP production in lymphocytes and inversely correlated with plasma noradrenaline level. 3. In 16 elderly non-smokers plasma noradrenaline was negatively correlated with the natural killer cell subset CD3–CD16+. Lymphocyte cAMP responses...
Abstract
1. We studied 37 healthy men at rest in the supine position to examine the effect of ageing, smoking and physical training on β 2 -adrenoceptor function, plasma catecholamines and the proportions of various lymphocyte subsets. 2. In 14 young subjects the proportion of natural killer cells was correlated with cAMP production in lymphocytes and inversely correlated with plasma noradrenaline level. 3. In 16 elderly non-smokers plasma noradrenaline was negatively correlated with the natural killer cell subset CD3–CD16+. Lymphocyte cAMP responses did not differ between young and elderly non-smokers, whereas plasma noradrenaline increased slightly but significantly with age. Physical training did not influence either plasma noradrenaline or adrenaline at rest or cAMP in lymphocytes. 4. In seven elderly long-term smokers cAMP production and the viability of lymphocytes were reduced. Plasma noradrenaline attained its highest values in long-term smokers. 5. It is concluded that cAMP production and plasma noradrenaline are related to lymphocyte subset composition. The greater the proportion of natural killer cells and related subsets, the higher is cAMP production and the lower is plasma noradrenaline. Thus, the inverse correlation between lymphocyte cAMP and plasma noradrenaline is indirect and most likely mediated by variability in lymphocyte subset composition. In elderly subjects, reduced cAMP production was observed in long-term smokers, and this abnormality was probably due to a reduced viability of lymphocytes and especially of natural killer cells. The negative correlation between the proportion of natural killer cells and plasma noradrenaline at rest contrasts with a well-known mobilizing effect of adrenaline on natural killer cells.
Articles
Marie-Cecile Jacobs, David S. Goldstein, Jacques J. Willemsen, Paul Smits, Theo Thien, Jacques W. M. Lenders
Clin Sci (Lond) (1996) 90 (5): 337-343.
Published: 01 May 1996
... catecholaminergic responses to lower body negative pressure depends on the intensity of the stimulus (−15 versus −40 mmHg). 2. In 14 healthy subjects, responses of forearm blood flow and noradrenaline spillover and of total body noradrenaline and adrenaline spillover were assessed during infusion of [ 3 H...
Abstract
1. Lower body negative pressure provides a means to examine neurocirculatory reflexive responses to decreases in venous return to the heart. We assessed whether the pattern of catecholaminergic responses to lower body negative pressure depends on the intensity of the stimulus (−15 versus −40 mmHg). 2. In 14 healthy subjects, responses of forearm blood flow and noradrenaline spillover and of total body noradrenaline and adrenaline spillover were assessed during infusion of [ 3 H]noradrenaline and [ 3 H]adrenaline during −15 and −40 mmHg of lower body negxative pressure. 3. During lower body negative pressure at −15 mmHg, heart rate and pulse pressure did not change, but forearm vascular resistance increased by 25–50%. Forearm noradrenaline spillover increased by about 50%, from 0.63 ± 0.16 to 0.94 ± 0.23 pmol min −1 100 ml −1 ( P <0.05). Total body noradrenaline spillover did not change, and total body adrenaline spillover increased significantly by about 30%. Clearances of noradrenaline and adrenaline were unchanged. 4. During lower body negative pressure at −40 mmHg, heart rate increased and pulse pressure decreased. Forearm vascular resistance increased by about 100%, and forearm noradrenaline spillover increased by 80%, from 0.73 ± 0.19 to 1.32 ± 0.36 pmol min −1 100 ml −1 ( P <0.05). Total body noradrenaline spillover increased by 30%, and total body adrenaline spillover increased by about 50%. Clearances of both noradrenaline and adrenaline decreased. 5. The results are consistent with the view that selective deactivation of cardiopulmonary baroreceptors during low-intensity lower body negative pressure increases sympathoneural traffic to forearm skeletal muscle and increases adrenomedullary secretion without a concomitant generalized increase in sympathoneural outflows. Concurrent deactivation of cardiopulmonary and arterial baroreceptors during high-intensity lower body negative pressure evokes a more generalized increase in sympathoneural activity, accompanied by further increased adrenomedullary secretion and decreased plasma clearances of noradrenaline and adrenaline. The findings support differential increases in skeletal sympathoneural and adrenomedullary outflows during orthostasis, with more generalized sympathoneural responses to systemic hypotension.
Articles
Clin Sci (Lond) (1995) 89 (4): 343-348.
Published: 01 October 1995
...Daniel Green; Gerry O'driscoll; Brian Blanksby; Roger Taylor 23 6 1995 23 6 1995 © 1995 The Biochemical Society and the Medical Research Society 1995 antioxidants blood flow cigarette smoking forearm nitric oxide noradrenaline Clinical Science (1995) 89, 343-348...
Articles
Helen S. Cox, David M. Kaye, Jane M. Thompson, Andrea G. Turner, Garry L. Jennings, Catherine Itsiopoulos, Murray D. Esler
Clin Sci (Lond) (1995) 89 (2): 145-154.
Published: 01 August 1995
... nervous activity in healthy, lean subjects. 2. In nine male subjects, noradrenaline spillover was measured from the heart, kidney and liver using isotope dilution, both while fasting and after consumption of a high-energy liquid meal of composition 53% carbohydrate, 32% fat and 15% protein (energy value...
Abstract
1. To investigate the link between post-prandial thermogenesis and sympathetic nervous activation we have studied the effects of a single large meal on regional sympathetic nervous activity in healthy, lean subjects. 2. In nine male subjects, noradrenaline spillover was measured from the heart, kidney and liver using isotope dilution, both while fasting and after consumption of a high-energy liquid meal of composition 53% carbohydrate, 32% fat and 15% protein (energy value 2.64–3.51 MJ). Regional oxygen consumption, whole-body oxygen consumption and, in a subset of subjects, muscle sympathetic nerve firing (microneurography) were also measured. 3. Both whole-body oxygen consumption ( P < 0.03) and total body spillover of noradrenaline ( P < 0.01) rose after the meal, with peak increases of 24% and 56% respectively. Spillover of noradrenaline from the heart was unchanged, that from the hepatosplanchnic circulation increased marginally (0.377 nmol/min to 0.480 nmol/min, P = 0.09), while renal noradrenaline spillover more than doubled (0.440 nmol/min to 0.937 nmol/min, P < 0.05). Skeletal muscle sympathetic nerve activity (peroneal nerve) increased from 7.7 bursts/min at rest to peak at 17.9 bursts/min 60 min after the meal in the three subjects in whom stable recordings were obtained. 4. The meal increased oxygen consumption in the kidneys and liver significantly, from 11.5 ± 1.6 ml/min to 14.5 ± 1.1 ml/min and from 46 ± 7 ml/min to 57 ± 6 ml/min respectively ( P < 0.05), but not in the heart. 5. Consumption of a large meal produces a substantial and relatively selective increase in sympathetic outflow to the kidneys and skeletal muscle. While resting regional oxygen consumptions and noradrenaline spillovers were related, the changes that occurred in each were unrelated, so that no direct relationship could be demonstrated between post-prandial thermogenesis and sympathetic activity.
Articles
Graeme Eisenhofer, Peter Friberg, Karel Pacak, David S. Goldstein, Dennis L. Murphy, Constantine Tsigos, Arshed A. Quyyumi, Han G. Brunner, Jacques W. M. Lenders
Clin Sci (Lond) (1995) 88 (5): 533-542.
Published: 01 May 1995
... from plasma measurements of these metabolites in a number of clinical conditions (hypertension, cardiac failure, bilateral adrenalectomy and X-chromosomal deletions of the gene for monoamine oxidase), and before and during activation of sympathetic outflow or infusions of noradrenaline and adrenaline...
Abstract
1. The clinical utility of plasma metadrenalines for examination of sympatho-adrenal function and catecholamine metabolism was assessed from plasma measurements of these metabolites in a number of clinical conditions (hypertension, cardiac failure, bilateral adrenalectomy and X-chromosomal deletions of the gene for monoamine oxidase), and before and during activation of sympathetic outflow or infusions of noradrenaline and adrenaline. 2. Plasma concentrations of normetadrenaline were less than 25% of those of noradrenaline, concentrations of metadrenaline and adrenaline were similar and those of sulphate-conjugated metadrenalines were 20- to 30-fold higher than free metadrenalines. Hypertensive patients had elevated plasma concentrations of adrenaline, noradrenaline and conjugated but not free metadrenalines. Cardiac failure patients had 2- to 4-fold increases in plasma noradrenaline and free and conjugated normetadrenaline. Adrenalectomy resulted in undetectable plasma concentrations of adrenaline, 91–97% decreases in free and conjugated metadrenaline and a 40% decrease in normetadrenaline relative to noradrenaline. Patients with X-chromosomal deletions of the gene for monoamine oxidase had 6- and 16-fold increases in plasma free and conjugated normetadrenaline and 2- and 4-fold increases in free and conjugated metadrenaline. 3. Infusion of catecholamines increased plasma concentrations of free metadrenalines by less than 6% of increases in precursor amines, indicating that most plasma normetadrenaline (84%) and metadrenaline (90%) is derived from metabolism of catecholamines before their entry into the circulation. Considerable O-methylation of catecholamines within the adrenals explains why sympatho-adrenal activation resulted in smaller proportional increases in plasma metadrenalines than catecholamines. 4. Plasma metadrenalines provide supplementary information about sympatho-adrenal activity to that provided by catecholamines, but are more useful for examination of the extraneuronal inactivation of catecholamines, particularly detection of neurochemical phenotypes in genetic disorders of catecholamine metabolism. Significant formation of metadrenalines within chromaffin tissue explains why measurements of plasma metadrenalines provide an extraordinarily sensitive method for diagnosis of phaeochromocytoma.
Articles
Clin Sci (Lond) (1995) 88 (5): 525-531.
Published: 01 May 1995
...Florence Wong; Arieh Bomzon; Alexander Logan; Laurence Blendis 1. This study assesses the effects of sodium status on venous responsiveness to noradrenaline and the neurohumoral profile in pre-ascitic cirrhotic patients. Eight cirrhotic patients and ten control subjects were studied after both a...
Abstract
1. This study assesses the effects of sodium status on venous responsiveness to noradrenaline and the neurohumoral profile in pre-ascitic cirrhotic patients. Eight cirrhotic patients and ten control subjects were studied after both a low (20 mmol/day) and a high (200 mmol/day) sodium diet. Venous responsiveness to increasing doses of noradrenaline in a dorsal hand vein and various plasma hormone levels were measured. Maximal response ( R max .) and the dose of noradrenaline that yielded 50% of R max (ED 50 ) were then calculated. 2. A significantly smaller dorsal hand vein diameter was observed in the control subjects on a low sodium (2.23 ± 0.14 mm) compared with a high sodium (2.57 ± 0.15 mm; P = 0.04) diet, but not in the cirrhotic patients. R max. was not significantly different in either group on both diets. With low sodium intake, ED 50 was similar in the two groups. However, on high sodium intake, control subjects had a significantly higher ED 50 (34.4 ± 7.4 ng/min) than the cirrhotic patients (5.03 ± 0.86 ng/min; P < 0.003). Plasma noradrenaline in the control subjects fell significantly with the change from a low (1.29 ± 0.11 nmol/l) to a high (0.68 ± 0.09 nmol/l; P < 0.001) sodium diet, but remained elevated in the cirrhotic patients. Cirrhotic patients had significantly higher atrial natriuretic factor levels and lower plasma renin activity than the control subjects on both diets. 3. In conclusion, pre-ascitic cirrhotic patients show no evidence of venodilatation. Their sympathetic nervous activity is not suppressible by volume expansion. Relative hyper-responsiveness of the peripheral venous circulation to adrenergic stimulation with high sodium intake is present.
Articles
Clin Sci (Lond) (1995) 88 (4): 421-426.
Published: 01 April 1995
... microvascular disease. We have previously found that vasoconstrictive responses to noradrenaline are exaggerated in insulin-dependent diabetic patients with microalbuminuria as compared with both normoalbuminuric insulin-dependent diabetic patients and non-diabetic control subjects. 2. To determine whether this...
Abstract
1. Microalbuminuria, the earliest clinical marker of microvascular disease, is an important predictor of early death in insulin-dependent diabetes, and abnormal vascular reactivity may contribute to microvascular disease. We have previously found that vasoconstrictive responses to noradrenaline are exaggerated in insulin-dependent diabetic patients with microalbuminuria as compared with both normoalbuminuric insulin-dependent diabetic patients and non-diabetic control subjects. 2. To determine whether this is due to increased sensitivity at α 1 - or α 2 -adrenergic receptors, we compared vascular responses to the α 1 -adrenergic agonist phenylephrine and the α 2 -adrenergic agonist clonidine. 3. We studied 15 insulin-dependent diabetic patients with microalbuminuria, 15 insulin-dependent diabetic patients with normal urinary albumin excretion and 14 non-diabetic subjects. Vascular constrictive responses were measured in dorsal hand veins. 4. No difference in vasoreactivity to phenylephrine was demonstrated between any of the three groups. However, enhanced vascular responsitivity to clonidine at infusion rates of 16–2048 ng/min (analysis of variance, P < 0.001) was found in insulin-dependent diabetic patients with microalbuminuria as compared with both non-diabetic control subjects and normoalbuminuric insulin-dependent diabetic patients. There were no significant differences between the dose—response curves of the diabetic group with normal urinary albumin excretion and the non-diabetic group. 5. Vasoconstriction mediated by α 2 -adrenergic receptors is therefore enhanced in normotensive insulin-dependent diabetic patients with microalbuminuria. If also present at the level of the peripheral resistance arterioles or the efferent glomerular arterioles, this could lead to systemic and intraglomerular hypertension, factors which may contribute to the development of diabetic nephropathy.
Articles
Clin Sci (Lond) (1995) 88 (4): 439-446.
Published: 01 April 1995
...Kjell Larsson; Per Carlens; Sture Bevegård; Paul Hjemdahl 1. Bronchoconstriction does not seem to be a stimulus for sympathoadrenal activation, as judged by venous plasma concentrations of noradrenaline, adrenaline or neuropeptide Y-like immunoreactivity. However, venous measurements have...
Abstract
1. Bronchoconstriction does not seem to be a stimulus for sympathoadrenal activation, as judged by venous plasma concentrations of noradrenaline, adrenaline or neuropeptide Y-like immunoreactivity. However, venous measurements have methodological drawbacks. In the present study arterial and mixed venous (pulmonary arterial) levels of these variables were determined before and after histamine-induced bronchoconstriction in non-medicated asthmatic subjects. In addition, noradrenaline kinetics in plasma (isotope dilution) and the pulmonary overflows of noradrenaline and neuropeptide Y-like immunoreactivity were determined. 2. Histamine inhalation induced bronchoconstriction; forced expiratory volume in 1 s decreased by 38.7% ± 4.1% (SE) and arterial P o 2 by 3.0 ± 0.9 kPa. This acute bronchoconstriction induced significant elevations of arterial and mixed venous plasma noradrenaline from ≤1.18 nmol/l to ≥1.40 nmol/l. The clearance of NA from plasma increased marginally. Thus, the arterial plasma NA response was due to increased spillover of noradrenaline to plasma (from 1.80 ± 0.18 to 2.52 ± 0.36 mmol min −1 /m 2 at maximal bronchoconstriction, with a subsequent further increase). There were no elevations of adrenaline or neuropeptide Y-like immunoreactivity in arterial plasma. 3. No sympathetic activation could be demonstrated in the lungs (pulmonary noradrenaline or neuropeptide Y-like immunoreactivity overflow), and no alterations in pulmonary vascular resistance or cardiac output were observed. Neither arterial nor mixed venous plasma concentrations of adrenaline were influenced by bronchoconstriction. 4. Acute bronchoconstriction thus leads to peripheral sympathetic activation (possibly due to the increased work of breathing) which does not involve the lungs. Adrenaline is not secreted in response to induced bronchoconstriction, and thus is of no functional importance as a counter-regulatory hormone in this situation.
Articles
Clin Sci (Lond) (1994) 87 (1): 69-74.
Published: 01 July 1994
... shamfeeding (with the sight and smell of an English breakfast) and for 5 h after they had ingested the meal (3514kJ, 50% fat, 35% carbohydrate). The post-obese women had maintained their normal body weight for at least 3 months before the study. 2. The plasma noradrenaline concentration was not different...
Abstract
1. Plasma pancreatic polypeptide, plasma catecholamine, blood glucose, plasma insulin and plasma peptide YY concentrations were studied to assess differences between eight formerly obese and eight never-obese control women during 25 min of shamfeeding (with the sight and smell of an English breakfast) and for 5 h after they had ingested the meal (3514kJ, 50% fat, 35% carbohydrate). The post-obese women had maintained their normal body weight for at least 3 months before the study. 2. The plasma noradrenaline concentration was not different between the groups either during fasting (post-obese women 0.08 ± 0.01 ng/ml versus control women 0.10 ± 0.01 ng/ml) or in the significant postprandial increase ( P < 0.001). The plasma adrenaline concentration increased significantly during sham-feeding in the control group from 0.024 ± 0.004 ng/ml to 0.033 ± 0.004 ng/ml ( P = 0.02) in contrast with the post-obese women, who had significantly lower plasma concentrations of adrenaline in the fasting state (post-obese 0.016 ± 0.003 ng/ml versus control women 0.024 ± 0.004 ng/ml, P = 0.003), during sham-feeding (post-obese women 0.018 ± 0.002 ng/ml versus control women 0.033 ± 0.004 ng/ml, P = 0.003) and in the postprandial increase ( P = 0.003). The maximal postprandial response concentrations recorded 5 h after the meal were 0.025 ± 0.003 ng/ml in post-obese women and 0.035 ± 0.004 ng/ml in control subjects ( P = 0.04). There were no significant differences in plasma pancreatic polypeptide, plasma peptide YY, plasma insulin, or blood glucose concentrations between the two groups. 3. The plasma adrenaline concentration is lower in post-obese women in the basal fasting state, during sham-feeding and in response to a meal. These results indicate that post-obese subjects respond differently to food stimulation than normal subjects.
Articles
Umberto Simeoni, Thierry Massfelder, Christian Saussine, Clément Judes, Jean Geisert, Jean-Jacques Helwig
Clin Sci (Lond) (1994) 86 (3): 245-249.
Published: 01 March 1994
... rabbit kidney perfused in the presence of indomethacin (10 μmol/l) and preconstricted with noradrenaline (7.2 nmol/min). 2. Under control conditions, bolus administrations of acetylcholine (10 μmol/l), an NO-dependent renal vasodilator, verapamil (0.1 mmol/l), an NO-independent renal vasodilator, and...
Abstract
1. The present study was designed to explore the role of NO derived from l-arginine in the vasodilatory response to synthetic human parathyroid hormone-related peptide-(1–34) in the isolated rabbit kidney perfused in the presence of indomethacin (10 μmol/l) and preconstricted with noradrenaline (7.2 nmol/min). 2. Under control conditions, bolus administrations of acetylcholine (10 μmol/l), an NO-dependent renal vasodilator, verapamil (0.1 mmol/l), an NO-independent renal vasodilator, and parathyroid hormone-related peptide (87 nmol/l) decreased the preconstriction pressure, by 31%, 71% and 43%, respectively. 3. Bolus administration of 100 μmol/l N G -nitro-l-arginine-methyl ester caused a 20% increment in the perfusion pressure of the noradrenaline-preconstricted kidney. N G -nitro-l-arginine methyl ester inhibited the vasodilatory effect of acetylcholine and parathyroid hormone-related peptide, by 68% and 44%, respectively, but did not alter the verapamil-induced vasodilatation. 4. Unlike l-arginine, the bolus administration of 1 μmol/l of a mono-substituted l-arginine derivative, N-α -benzoyl-l-arginine ethyl ester, durably decreased the noradrenaline/ N G -nitro-l-arginine methyl ester-induced preconstriction by 57%. 5. Both l-arginine and N-α -benzoyl-l-arginine ethyl ester effectively reversed the inhibition induced by N G -nitro-l-arginine methyl ester on the vasodilatation elicited by acetylcholine and parathyroid hormone-related peptide. 6. In conclusion, the formation of NO from l-arginine contributes a substantial part to the vasodilatory action of parathyroid hormone-related peptide. Therefore, parathyroid hormone-related peptide appears to have a place among the renal haemodynamically active substances, whose vasodilatory actions are tuned by NO.
Articles
Clin Sci (Lond) (1994) 86 (2): 177-184.
Published: 01 February 1994
...A. Kurpad; K. Khan; A. G. Calder; S. Coppack; K. Frayn; I. MaCdonald; M. Elia 1. The effect of infusion of noradrenaline (0.42 μmol min −1 kg −1 ) on the exchange of non-esterified fatty acids, glycerol and other metabolites across subcutaneous abdominal adipose tissue was investigated in five...
Abstract
1. The effect of infusion of noradrenaline (0.42 μmol min −1 kg −1 ) on the exchange of non-esterified fatty acids, glycerol and other metabolites across subcutaneous abdominal adipose tissue was investigated in five healthy subjects using an arteriovenous catheterization technique and measurement of adipose tissue blood flow using the 133 Xe clearance technique. At the same time, the net rate of fat oxidation in the whole body was assessed by indirect calorimetry, and the turnover of glycerol in the whole body and in subcutaneous adipose tissue was estimated using [5- 2 H]glycerol, which was administered as a primed constant infusion for 1 h before (basal turnover) noradrenaline administration and continued during the 1 h of noradrenaline infusion. 2. The noradrenaline infusion increased the plasma noradrenaline concentration from a basal value of 0.9 ± 0.1 to 12.6 ± 1.2 nmol/(mean ± SEM) at 60 min. It also increased the arterialized concentration of glycerol by 50% (basal value 81 ± 11/μmol/l −1 ) and that of plasma non-esterified fatty acids three-fold (basal value 357 ± 86 μmol/l). 3. Noradrenaline increased the net release of glycerol by adipose tissue three-fold and that of non-esterified fatty acids three- to four-fold. Although the ratio of non-esterified fatty acid to glycerol release by adipose tissue increased in all subjects from a mean value of 2.7 in the basal period to 3.6 and 3.9 at 50 and 60 min of the noradrenaline infusion, respectively ( P < 0.02), at no time point did the ratio differ significantly from 3.0 4. Noradrenaline increased the estimated rate of appearance of glycerol in the whole body from a basal value of 1.5 ± 0.3 to 2.6 ± 0.3 μmol min −1 kg −1 body weight, and the net rate of triacylglycerol oxidation from 1.2 ± 0.1 to 1.7 ± 0.13 μmol min −1 kg −1 . The enrichment of glycerol in venous blood draining adipose tissue was two-fold lower than that predicted from the net addition of glycerol to the blood in the basal period ( P < 0.02). 5. This study provides a direct demonstration of a ‘hormone’ stimulating lipolysis in human adipose tissue in viva The effect of noradrenaline in significantly increasing the ratio of non-esterified fatty acid to glycerol release by adipose tissue may be partly explained by accumulation in adipose tissue of diacylglycerol, which is associated with release of non-esterified fatty acids but not glycerol. Finally, since the low enrichment of glycerol in venous blood draining adipose tissue cannot be entirely explained by the net addition of glycerol in adipose tissue, there must be exchange between enriched glycerol in blood and unenriched glycerol in adipose tissue. This raises questions about the accuracy of glycerol turnover studies, which are typically carried out over 1 h.
Articles
Daniel T. O'Connor, Justine H. Cervenka, Richard A. Stone, Gail L. Levine, Robert J. Parmer, Rebecca E. Franco-Bourland, Ignacio Madrazo, Philip J. Langlais, David Robertson, Italo Biaggioni
Clin Sci (Lond) (1994) 86 (2): 149-158.
Published: 01 February 1994
... central α 2 -agonist clonidine at a dose that diminished cerebrospinal fluid noradrenaline, nor did cerebrospinal fluid dopamine β-hydroxylase correspond between subjects to cerebrospinal fluid concentrations of noradrenaline or methoxyhydroxyphenylglycol; thus, cerebrospinal fluid dopamine β-hydroxylase...
Abstract
1. Dopamine β-hydroxylase is stored and released with catecholamines by exocytosis from secretory vesicles in noradrenergic neurons and chromaffin cells. Although dopamine β-hydroxylase enzymic activity is measurable in cerebrospinal fluid, such activity is unstable, and its relationship to central noradrenergic neuronal activity in humans is not clearly established. To explore the significance of cerebrospinal fluid dopamine β-hydroxylase, we applied a homologous human dopamine β-hydroxylase radioimmunoassay to cerebrospinal fluid, in order to characterize the properties and stability of cerebrospinal fluid dopamine β-hydroxylase, as well as its relationship to central noradrenergic neuronal activity and its variation in disease states such as hypertension, renal failure, Parkinsonism and congenital dopamine β-hydroxylase deficiency. 2. Authentic, physically stable dopamine β-hydroxylase immunoreactivity was present in normal human cerebrospinal fluid at a concentration of 31.3 ± 1.4 ng/ml (range: 18.5–52.5 ng/ml), but at a 283 ± 27-fold lower concentration than that found in plasma. Cerebrospinal fluid and plasma dopamine β-hydroxylase concentrations were correlated ( r = 0.67, P = 0.001). Some degree of local central nervous system control of cerebrospinal fluid dopamine β-hydroxylase was suggested by incomplete correlation with plasma dopamine β-hydroxylase (with an especially marked dissociation in renal disease) as well as the lack of a ventricular/lumbar cerebrospinal dopamine β-hydroxylase concentration gradient. 3. Cerebrospinal fluid dopamine β-hydroxylase was not changed by the central α 2 -agonist clonidine at a dose that diminished cerebrospinal fluid noradrenaline, nor did cerebrospinal fluid dopamine β-hydroxylase correspond between subjects to cerebrospinal fluid concentrations of noradrenaline or methoxyhydroxyphenylglycol; thus, cerebrospinal fluid dopamine β-hydroxylase concentration was not closely linked either pharmacologically or biochemically to central noradrenergic neuronal activity. 4. Cerebrospinal fluid dopamine β-hydroxylase was not changed in essential hypertension. In Parkinson's disease, cerebrospinal fluid dopamine β-hydroxylase was markedly diminished (16.3 ± 2.9 versus 31.3 ± 1.4 ng/ml, P < 0.001) and rose by 58 ± 21% ( P = 0.02) after adrenal-to-caudate chromaffin cell autografts. In congenital dopamine β-hydroxylase deficiency, lack of detectable dopamine β-hydroxylase immunoreactivity in cerebrospinal fluid or plasma suggests absent enzyme (rather than a catalytically defective enzyme) as the origin of the disorder. 5. We conclude that cerebrospinal fluid dopamine β-hydroxylase immunoreactivity, while not closely linked to central noradrenergic neuronal activity, is at least in part derived from the central nervous system, and that its measurement may be useful in both the diagnosis and treatment of neurological disease.
Articles
Clin Sci (Lond) (1994) 86 (2): 203-208.
Published: 01 February 1994
... displacement technique. 3. Basal forearm blood flow was increased and vascular resistance was decreased in the patients with alcoholic cirrhosis compared with healthy control subjects. Noradrenaline and N G -monomethyl-l-arginine caused dose-dependent falls in forearm blood flow in both healthy control...
Abstract
1. Nitric oxide (NO) is a potent endogenous vasodilator and plays a role in the control of resting vascular tone. Patients with cirrhosis have a hyperdynamic circulation with reduced blood pressure and decreased peripheral resistance, and it is possible that increased production of NO due to induction of NO synthase may be involved in maintaining this vasodilatation. We have examined this possibility by studying the effects of local infusions of N G -monomethyl-l-arginine (an inhibitor of NO synthase) in the forearm arteriolar bed and the superficial dorsal hand veins of patients with alcoholic cirrhosis. 2. Drugs were either infused locally into the brachial artery and forearm blood flow was measured by venous occlusion plethysmography, or into a vein on the back of the hand and vein diameter was measured using a linear displacement technique. 3. Basal forearm blood flow was increased and vascular resistance was decreased in the patients with alcoholic cirrhosis compared with healthy control subjects. Noradrenaline and N G -monomethyl-l-arginine caused dose-dependent falls in forearm blood flow in both healthy control subjects and patients with cirrhosis. There was no significant difference in the responses to either noradrenaline or N G -monomethyl-l-arginine between the two groups. 4. In the superficial hand veins there was no change in vein size in response to N G -monomethyl-l-arginine infused alone, and venoconstriction to local infusion of noradrenaline was unaffected by co-infusion with N G -monomethyl-l-arginine. 5. Our results confirm that patients with alcoholic cirrhosis are vasodilated compared with healthy control subjects. Our findings show that basal NO-mediated vasodilatation occurs in the forearm arterial bed, but not the superficial hand veins, of these patients. However, since the response to local NO synthesis inhibition was similiar in the two groups, increased production of NO due to induction of NO synthase is unlikely to account fully for the vasodilatation seen in patients with mild to moderate alcoholic cirrhosis.
Articles
Clin Sci (Lond) (1994) 86 (1): 35-41.
Published: 01 January 1994
... stress. 2. To assess the biological variability within individuals, ten subjects were sampled on five occasions over 8–30 h. The intra-individual coefficients of variation for plasma and platelet noradrenaline levels were 193 +10% and 9.5 +4.2%, respectively, and for plasma and platelet adrenaline levels...
Abstract
1. Four studies were designed to test the hypothesis that platelet catecholamine levels may provide a stable index of circulating plasma catecholamine concentrations, and that these are unaffected by acute elevations of plasma levels with physical and psychological stress. 2. To assess the biological variability within individuals, ten subjects were sampled on five occasions over 8–30 h. The intra-individual coefficients of variation for plasma and platelet noradrenaline levels were 193 +10% and 9.5 +4.2%, respectively, and for plasma and platelet adrenaline levels 48.3 +22% and 25.3 +8.4%, respectively. 3. Three other studies investigating the response to physical and psychological stress were performed. In the first study, plasma and platelet catecholamine levels were studied in 12 healthy subjects before and after bicycle ergometry. Plasma catecholamine concentrations increased [noradrenaline by +346 + 323% ( P = 0.002) and adrenaline by +314 + 352% (P - 0.003)], whereas platelet concentrations showed little change [noradrenaline +4+18% ( P = 0.94) and adrenaline +38+ 116% ( P = 0.67)]. 4. In the study, catecholamine concentrations were measured in eight subjects after hand immersion in iced water. Plasma noradrenaline concentrations increased significantly (+58 +19%, P = 0.001), but no significant change was found in plasma adrenaline concentrations (+8+44%, P = 0.48). Platelet catecholamine concentrations showed no significant change (noradrenaline +15 +15%, P = 0.052, and adrenaline 19 +82%, P = 0.84). 5. In the third study, catecholamine concentrations were measured in 22 medical students before and after their end-of-year examination. There was no significant change in plasma noradrenaline or adrenaline concentrations (+20 +39%, P = 0.08, and −2 +33%, P = 0.36, respectively) nor in platelet concentrations (noradrenaline +6+19%, P = 0.15, and adrenaline +34 +72, P = 0.65). 6. In 53 subjects sampled between 08.00 and 12.00 hours, plasma and platelet noradrenaline concentrations were significantly correlated ( r , = 0.47, P <0.001), but the relationship between plasma and platelet adrenaline concentrations in these subjects did not achieve significance ( r s = 0.17, P <0.23). 7. In conclusion, platelet catecholamine concentrations seem to be unaffected by acute short-term stress and may provide a reliable indicator of chronic sympatho-adrenomedullary arousal.
Articles
Clin Sci (Lond) (1993) 85 (1): 45-49.
Published: 01 July 1993
...-individual variability of cardiovascular and plasma noradrenaline responses to sustained isometric contraction. 3. The results of this study indicate that inter-individual variability is generally greater than intra-individual variability. Diastolic blood pressure was the most sensitive as well as the least...
Abstract
1. Eight healthy adult males underwent three sustained isometric contractions at 30% of maximal voluntary contraction for 3 min, within a 9 day period. 2. The study focuses on the inter-individual and day-to-day intra-individual variability of cardiovascular and plasma noradrenaline responses to sustained isometric contraction. 3. The results of this study indicate that inter-individual variability is generally greater than intra-individual variability. Diastolic blood pressure was the most sensitive as well as the least variable cardiovascular parameter measured. 4. The variability of plasma noradrenaline levels in both the basal and the stimulated state was high. The present study suggests that it is preferable to determine the ‘true’ noradrenaline peak after the release of handgrip, as this is associated with a lower variability than the plasma noradrenaline peak taken at the time of the release of handgrip.
Articles
Clin Sci (Lond) (1993) 84 (4): 413-417.
Published: 01 April 1993
...Alastair J. McCance; J. Colin Forfar 1. To investigate the effects of acute β 1 -adrenoceptor blockade on sympathetic nervous activity, cardiac and whole-body noradrenaline kinetics were determined during intravenous infusions of saline placebo and of metoprolol (10-15 mg plus 150 μg min −1 kg −1...
Abstract
1. To investigate the effects of acute β 1 -adrenoceptor blockade on sympathetic nervous activity, cardiac and whole-body noradrenaline kinetics were determined during intravenous infusions of saline placebo and of metoprolol (10-15 mg plus 150 μg min −1 kg −1 ) in 10 patients undergoing diagnostic cardiac catheterization, in whom β-adrenoceptor antagonists had been discontinued for 7 days. 2. Coronary haemodynamics were measured in these 10 patients plus two others. Compared with saline placebo, metoprolol administration was associated with decreases in heart rate (68 ± 2 to 59 ± 3 beats/min, P < 0.001) and coronary sinus blood flow (86 ± 8 to 68 ± 6 ml/min, P < 0.001) and an increase in calculated coronary vascular resistance (1.42 ± 0.19 to 1.75 ± 0.22 mmHg min ml −1 , P < 0.001). Arterial and femoral venous noradrenaline concentrations, whole-body noradrenaline clearance and whole-body noradrenaline spillover to arterial plasma did not change. In contrast, cardiac noradrenaline spillover (33.7 ± 5.1 to 20.2 ± 4.3 pmol/min, P < 0.05) and cardiac noradrenaline clearance (31 ± 3 to 23 ± 3 ml/min, P < 0.001) were significantly decreased during metoprolol administration. 3. These results may be explained by inhibition of pre-junctional facilitatory β-adrenoceptors, which we hypothesize may be predominantly of the β 1 -subtype in the heart and of the β 2 -subtype in the periphery.