During positive pressure mechanical ventilation, percentile systolic pressure variation (%SPV) or respiratory-related arterial pressure variability (RAPV) have both been used in assessment of graded haemorrhage. We aimed to investigate whether changes in %SPV and RAPV are correlated during graded haemorrhage (by 5, 10 or 20% of the estimated blood volume) in anaesthetized positive pressure ventilated rats and to investigate the involvement of autonomic regulation. Saline vehicle or atropine produced no discernible effect on baseline %SPV or RAPV but, thereafter, %SPV and RAPV increased progressively with graded haemorrhage. Propranolol significantly decreased baseline %SPV and RAPV and changes induced in %SPV and RAPV by graded haemorrhage. Phentolamine significantly enhanced baseline %SPV and RAPV, and further enhancement of %SPV and RAPV by graded haemorrhage did not occur until 20% of the estimated blood volume was removed. RAPV was significantly correlated with %SPV in all experimental groups. We conclude that RAPV is comparable with%SPV as an indicator of graded haemorrhage and that, in anaesthetized and positive pressure ventilated rats, both are dependent on autonomic function, especially β-adrenoceptors.

Congestive heart failure (CHF) is characterized by a sympathetic activation and a baroreflex impairment whose degree is directly related to the clinical severity of the disease. However, whether these abnormalities vary according to the ischaemic or idiopathic dilated nature of the CHF state has not been conclusively documented. In patients with a clinically stable, chronic CHF state in New York Heart Association functional class II and III, due either to ischaemic heart disease (IHD; n = 22, age 60.3±2.4 years, means±S.E.M.) or to idiopathic dilated cardiomyopathy (IDC; n = 20, age 58.9±2.8 years), and in 30 age-matched controls, we measured arterial blood pressure (using a Finapres device), heart rate (by electrocardiogram) and postganglionic muscle sympathetic nerve traffic (by microneurography) at rest and during baroreceptor manipulation induced by the vasoactive drug-infusion technique. Blood pressure values were not significantly different in CHF patients and controls. Compared with controls, heart rate was similarly increased and left ventricular ejection fraction (by echocardiography) similarly reduced in CHF patients with IHD or IDC. Muscle sympathetic nerve traffic was significantly greater in CHF patients than in controls, and did not differ between patients with IHD or IDC (67.3±4.2 and 67.8±3.8 bursts/100 heart beats respectively). This was also the case for the degree of baroreflex impairment. These data show that CHF states due to IHD or to IDC are characterized by a similar degree of peripheral sympathetic activation and by a similar impairment of the baroreflex function. Thus the neuroadrenergic and reflex abnormalities characterizing CHF are independent of its aetiology.

The purpose of this study was to evaluate the autonomic response to standard haemodialysis and the changes associated with the onset of intradialytic hypotension in 12 normotensive patients with uraemia. Power spectra of R–R interval and of blood pressure fluctuations were obtained during a standard dialysis session and estimated in the low-frequency (LF, 30–150 ;mHz) and high-frequency (HF, 150–400 ;mHz) range. The absolute power of the LF component of blood pressure variations and the LF/HF ratio of R–R interval were assumed as indexes of sympathetic activity. Standard haemodialysis induced hypotension in six patients (unstable) while a minor pressure decline was present in the other six (stable). Normalized blood volume before dialysis and percentage volume reduction were similar in the two groups. Tachycardia in response to pressure and volume decrease was more pronounced in stable than in unstable patients, as evidenced by a higher slope of the relation between R–R interval and systolic blood pressure (7.9 versus 0.9 ;ms/mmHg, P < 0.01). Sympathetic tone was enhanced during early dialysis in all patients (+2±1 for R–R LF/HF ratio, +2.4±0.6 ;mmHg 2 and +7.2±2 ;mmHg 2 for absolute LF power of diastolic and of systolic blood pressure respectively, P < 0.05), compared with baseline predialysis values. During late dialysis, unstable patients showed an impairment of sympathetic activation which preceded hypotension and was maximal during the crisis (-2.9±1.4 for R–R LF/HF ratio, -2.7±1.4 ;mmHg 2 and -8.6±4.0 ;mmHg 2 for absolute LF power of diastolic and of systolic blood pressure respectively, P < 0.05). On the contrary, stable patients showed constantly elevated indexes (+3.7±1.4 for R–R LF/HF ratio, +5.9±2.7 ;mmHg 2 and +13.3±6.2 ;mmHg 2 for LF of diastolic and of systolic blood pressure, P < 0.05). Values returned to predialysis levels after the end of the dialysis session in all patients. We conclude that standard haemodialysis activates a marked and reversible sympathetic response in both stable and unstable uraemic patients. However, in unstable patients, such activation is impaired in late dialysis, therefore contributing to the onset of the hypotensive crisis.

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.

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.

1. We assessed the effects of changing levels of sympathetic drive on the gain of baroreflex control of the sino-atrial node, in normotensive and hypertensive subjects. 2. Autoregressive spectral and cross-spectral analysis of R—R interval and systolic arterial pressure (non-invasive Finapres method) variabilities providing an estimate of baroreflex gain through the frequency domain index α were performed on data from 63 normotensive and 78 mild hypertensive subjects. Subjects were studied at rest and during active orthostatism, which induces sympathetic predominance. Seven control subjects and 14 hypertensive subjects were also studied after chronic atenolol treatment, to attenuate β-adrenoceptor-mediated responses. 3. In both normotensive and hypertensive subjects, the index α was reduced by active standing and increased by chronic β-adrenoceptor blockade. Furthermore, at rest, the index at was correlated with R—R variance and appeared significantly reduced with age. The age-related negative correlation of the index α was no longer evident during the standing-induced increase in sympathetic drive, in both normotensive and hypertensive subjects. 4. The index α, a non-invasive frequency domain estimate of the overall gain of baroreflex control of the sino-atrial node, which appears to be reduced in essential hypertension, is negatively modulated by physiological increases in sympathetic drive, and augmented by pharmacological blockade of β-adrenoceptors. 5. In essential hypertension the enhanced sympathetic drive present already at rest, and the simultaneous reduction of the gain of baroreflex mechanisms, are the expression of a complex alteration in neural cardiovascular control.

1. Plasma concentrations of noradrenaline and adrenaline were measured radioenzymatically in nine subjects during 4 min pressor and depressor responses (intra-arterial measurements) induced by increasing and reducing sympathetic vasoconstrictor tone via carotid baroreceptor deactivation and stimulation (neck chamber technique). 2. During the pressor response (15 ± 3 mmHg, mean ± se) plasma noradrenaline and adrenaline showed various changes in the different subjects and on average were not significantly increased above control. During the depressor response (−9 ± 2 mmHg) plasma noradrenaline and adrenaline also showed various changes in the subjects and were on average not significantly reduced below control. 3. In contrast the same subjects all showed an increase in noradrenaline and adrenaline (average 76 and 117%) at the fourth minute of a tilting manoeuvre with- a return to pretilting values no more than 4 min after resumption of the supine position. 4. These results suggest that the moderate and/or restricted alterations in sympathetic tone produced by manipulating a single baroreflex, though capable of affecting blood pressure, are not reflected by alterations in plasma catecholamines. To modify these humoral indices significantly, the more drastic or more diffuse alterations in sympathetic activity that may be produced by manipulating low as well as high pressure reflexogenic areas are needed.

1. Partial replacement of sodium by potassium in the diet attenuates the rise in blood pressure in stroke-prone spontaneously hypertensive rats (SHR-SP). 2. The blood pressure-lowering effect of potassium cannot be ascribed to a reduction in intravascular volume. 3. The increased dietary intake of potassium leads to a reduced stimulation of the sympathoneuronal and sympathoadrenal system by cold compared with the response of sodium-loaded rats. 4. The impaired inactivation of noradrenaline observed in sodium-loaded SHR-SP is improved in SHR-SP on a potassium-substituted diet. 5. It is concluded that changes in dietary intake of sodium and potassium modulate sympathetic activity and the metabolism of noradrenaline, both of which are related to the development of hypertension in SHR-SP.

1. The antihypertensive effect of 4 weeks' treatment with prizidilol (SKF 92657) (mean dosage 520 mg once or twice daily) was studied in ten essential hypertensive patients. 2. Both systolic and diastolic blood pressure were significantly reduced in all cases. Supine heart rate did not change, and in the erect position heart rate was significantly lowered. 3. Blood pressure reduction was due to peripheral vasodilatation, as the cardiac index increased after 4 weeks of prizidilol treatment. 4. After prizidilol plasma noradrenaline and adrenaline increased significantly, and PRA and plasma aldosterone were reduced. Although plasma volume increased, body weight did not change. 5. Cardiac performance, as evaluated by the PEP/LVET ratio, improved after treatment with prizidilol.

1. The validity of plasma noradrenaline as an index of sympathetic nervous activity was assessed by estimating variation in individual organ contribution to circulating concentrations. 2. Arteriovenous (A—V) differences in noradrenaline and adrenaline concentration were measured across several organs in nine patients with mild essential hypertension, in five with renal artery stenosis and 15 phaeochromocytoma patients. 3. In patients with phaeochromocytomas the percentage extraction of noradrenaline and adrenaline (estimated from the A—V differences) was similar across all organs, suggesting that adrenaline extraction could be used as a marker for noradrenaline extraction. 4. In the non-tumour patients the A—V difference for noradrenaline was less than that for adrenaline across most organs studied, reflecting the net result of noradrenaline release and extraction. The estimated contribution of various organs to the noradrenaline concentrations in their venous effluent was: heart. 21%; kidney 47%; legs 68%. 5. This pattern of A—V difference proved a positive diagnostic feature for non-tumour patients since it was not found even in the patients with small phaeochromocytomas, whose peripheral venous noradrenaline concentration alone did not distinguish them. 6. The venous-arterial difference across the adrenal glands of non-tumour patients was more than 10-fold greater for adrenaline than that for noradrenaline. Since the mean arterial concentration of noradrenaline was more than fivefold higher than that of adrenaline, the normal adrenal contribution to circulating noradrenaline is likely to be less than 2%. 7. In the patients with renal artery stenosis renal venous concentrations of noradrenaline (from the ischaemic kidney) were higher than arterial values, but mean arterial values were no higher than in the essential hypertensive patients. 8. Local variations in sympathetic activity may occur without altering the plasma noradrenaline concentration measured in peripheral plasma.

1. Plasma noradrenaline concentrations and blood pressure were measured in 45 patients with essential hypertension and 34 matched normotensive subjects. Plasma noradrenaline was similar in both groups, but in the hypertensive patients plasma noradrenaline correlated with blood pressure. 2. The increase in forearm flow in response to an intra-arterial infusion of phentolamine was determined in 12 of the hypertensive and 14 of the normotensive subjects to assess the α-adrenoceptor-mediated component of vascular resistance. Although the dilator response to phentolamine was similar in both groups, in the hypertensive patients it was correlated with the control plasma noradrenaline ( r = 0.83, P <0.01) as well as the height of mean blood pressure ( r = 0.73, P <0.01). 3. These results suggest that in hypertensive patients plasma noradrenaline can be a marker for both sympathetic activity and the α-adrenoceptor-mediated component of vascular resistance.

1. Salt loading accelerates and increases the rise in blood pressure (spSH) in stroke-prone spontaneously hypertensive rats, but not in Wistar-Kyoto (WK) rats. 2. In both strains a slight increase in plasma volume was obtained during salt loading. 3. Salt loading caused a distinct increase in plasma noradrenaline concentration in spSH rats, but a slight decrease in WK rats. Plasma adrenaline and dopamine concentrations remained unaffected. 4. Exposure to cold resulted in a more marked stimulation of sympathoadrenal and sympathoneuronal activity in salt-loaded spSH rats than in spSH rats on a normal sodium diet. 5. It is concluded that salt loading results in a further increase of the already elevated sympathetic activity in spSH rats.

1. Twelve asymptomatic young men with ‘primary’ T-wave aberrations in the electrocardiogram (group T) and 13 matched controls were subjected to a mental stress test, isometric exercise and a cold pressor test. 2. Plasma catecholamines and haemodynamics were studied. 3. Group T had signs of increased sympathetic activity at rest and enhanced sympatho-adrenal reactivity during stress. 4. Systolic blood pressure was consistently elevated in group T. 5. The T-wave aberrations may be explained by the increased sympathetic activity. 6. Several similarities exist between group T and borderline hypertensive subjects.

1. Forearm venous plasma noradrenaline, heart rate and intra-arterial blood pressure were measured sequentially during and after upright bicycle exercise in five normotensive and six hypertensive patients. 2. Plasma noradrenaline increased significantly between 4 and 8 min during exercise. 3. On stopping exercise blood pressure and heart rate decreased rapidly whilst plasma noradrenaline increased in each subject to reach a maximum at a median time of 108 s after exercise. 4. Plasma noradrenaline decreased in five of six normotensive patients between the end of exercise and 2 min after exercise performed in the supine position. 5. Evidence in favour of a reflex increase in sympathetic activity after upright exercise is discussed.

1. Slight decreases and increases in carotid baroreceptor activity were induced in subjects with essential hypertension by slight alterations in carotid transmural pressure (variable pressure neck-chamber technique) in order to obtain limited increases and reductions in sympathetic adrenergic activity. 2. When sympathetic activity was reflexly increased there was a rise in arterial pressure but no significant increase in plasma catecholamines. Likewise when sympathetic activity was reflexly reduced there was a fall in arterial pressure but no significant reduction in plasma catecholamines. 3. Plasma noradrenaline and adrenaline significantly and markedly increased in the same subjects when sympathetic activity was increased by activation of both arterial and low pressure baroreceptor reflexes with tilting. 4. It is suggested that measurements of catecholamines in systemic plasma may reveal marked degrees of sympathetic activation but may not be a sensitive index of more moderate changes in sympathetic tone.

1. Recordings have been obtained from single sympathetic fibres to the left kidney in anaesthetized adult spontaneously hypertensive (SH) rats and Wistar—Kyoto normotensive (WK) rats. 2. Under control conditions SH rats had a mean sympathetic activity of 3·3 ± se 0·45 Hz and WK rats 1·6 ± 0·23 Hz. During noradrenaline infusion single fibre discharge decreased graudally to low levels in both SH and WK rats. The absolute decrease in fibre activity/mmHg rise of arterial pressure was greater in SH rats than in WK rats, but the reverse was true when the discharge reduction was expressed as a percentage change. 3. Recordings have also been obtained from the left splanchnic nerve in awake SH and WK rats. Upon volume load with blood, in SH rats the sympathetic activity decreased significantly more than in WK rats. 4. Thus the sympathetic discharge to the kidneys is higher in SH rats than in WK rats. Upon volume load SH rats show an exaggerated reflex response, probably due to an augmented volume-receptor response.

1. The effect of physical exercise on blood pressure, plasma catecholamines and plasma renin activity was studied in fourteen patients with essential hypertension and in eight healthy subjects. 2. Resting plasma noradrenaline and adrenaline and plasma renin activity of the hypertensive patients did not differ from those of the control subjects. 3. In response to graded exercise producing successive heart rates of 120, 140 and 160 beats/min, significantly greater increases of blood pressure were found in the patients than in the control subjects. 4. Plasma noradrenaline increased significantly in both groups at all levels of exercise, the responses being significantly greater in the hypertensive patients. 5. The mean arterial blood pressure was significantly correlated with plasma noradrenaline concentration in the control subjects but not in the hypertensive patients. 6. In the hypertensive group plasma adrenaline increased significantly after exercise at all work loads whereas, in the control group, significant increase occurred only at the highest work load. The differences in the response of the two groups were significant at each work load. 7. Plasma renin activity increased significantly after exercise at the heart rate of 120 beats/min, both in the hypertensive patients and in the control subjects. The magnitude of the response was similar in the two groups.

1. Mean plasma noradrenaline concentration was elevated in forty-four patients with established essential hypertension. Eighteen of these hypertensive patients had resting plasma noradrenaline concentrations in the normal range. 2. Patients with endogenous depression had higher mean plasma noradrenaline concentrations but significantly lower blood pressure than patients with essential hypertension. 3. Patients with phaeochromocytoma had plasma noradrenaline concentrations twenty-eight times greater than those found in essential hypertension, but blood pressures were less than 20% higher. 4. It is concluded that excess of sympathetic drive only partly explains the level of the blood pressure in essential hypertension.