The critical phase during cardiosurgical procedures is weaning the diseased heart from the ECC (extracorporeal circulation). Post-ischaemic heart failure sometimes requires the administration of inotropic and/or vasconstrictive agents. The natriuretic peptides influence pre- and after-load through their natriuretic, diuretic and vasodilating actions. To date, there are only a few reports describing the therapeutic effect of BNP (brain natriuretic peptide) administration during cardiosurgical procedures. The aim of the present study was to evaluate the effect of BNP administration following ECC in an animal model. Surgery was performed on 20 pigs using ECC. A 30-min ischaemic episode was simulated. Following de-clamping, BNP was administered to the BNP group ( n =10) by an i.v. (intravenous) bolus at 0.3 μg·kg −1 of body weight·min −1 , followed by an infusion at a rate of 0.015 μg·kg −1 of body weight·min −1 for 60 min. The animals in the control group ( n =10) received a saline solution instead of BNP. Haemodynamic and clinical chemistry parameters as well as the amount of catecholamines that were required were measured. All of the animals in the BNP group had a significantly better cardiac output and cardiac index at the end of the experiment. Seven out of 10 animals from the control group required catecholamines, whereas only one animal from the BNP group did. Creatine kinase levels were significantly lower in the BNP group. Systemic vascular resistance was markedly lower in the BNP group. In conclusion, administration of BNP is highly effective in treating post-ischaemic heart failure following ECC. Haemodynamics are greatly improved, and there is almost no need for pharmacological support.

The aim of the present study was to examine gene expression and protein concentrations of β 1 - and β 2 -adrenergic receptors in subcutaneous adipose tissue in obese subjects in response to weight loss. Eighteen obese subjects were studied during diet-induced weight loss. β-Adrenergic receptor mRNA levels were quantified by reverse transcription-PCR–HPLC. β-Adrenergic receptor protein concentrations were measured by Western blotting using fluorescence laser scanning for detection. Subjects lost 12.8±0.8 kg (mean±S.E.M.) during diet treatment. There was a 34% decrease in the β 1 -adrenergic receptor mRNA level (0.92±0.09 compared with 0.61±0.06 amol/μg of DNA; P <0.002). β 2 -Adrenergic receptor mRNA did not decrease significantly. β 2 -Adrenergic receptor protein concentration decreased 37% (25.5±7.1 compared with 16.0±5.6 arbitrary units/ng of DNA; P =0.008), whereas β 1 -adrenergic receptor protein concentration did not decrease significantly. The degree of weight loss was correlated with the concentration of β 1 -adrenergic receptor protein ( r =0.65, P <0.003) and changes in receptor protein concentration ( r =0.50, P =0.035) during the very-low-calorie diet. In conclusion, the present study demonstrates a relationship between β 1 -adrenergic receptor protein concentration in adipose tissue and the degree of weight loss. This relationship is not directly related to energy expenditure and deserves further investigation.

Sustained effects of SNS (sympathetic nervous system) and HPAA (hypothalamic–pituitary–adrenal axis) hyperactivity on haemostasis have not been investigated. In the present study, we tested for an association of overnight urinary catecholamine and cortisol excretion with morning plasma levels of fibrinogen, PAI-1 (plasminogen activator inhibitor-1) and D-dimer. Participants (639 male industrial employees) with a complete dataset were studied (age, 41±11 years; mean±S.D.). Subjects collected overnight urinary samples and had a fasting morning blood sample drawn. Measurement of urinary adrenaline (epinephrine), noradrenaline (norepinephrine) and cortisol were dichotomized to perform multivariate analyses of (co)variance. Haemostatic parameters were measured by ELISA. Fibrinogen was higher in men with high adrenaline ( F 7,631 =5.68, P =0.018; where the subscripted value represents the degrees of freedom) and high noradrenaline ( F 7,631 =4.19, P =0.041) compared with men with low excretion of the respective hormones. PAI-1 was higher in men with high cortisol than in men with low cortisol ( F 7,631 =4.77, P =0.029). Interaction revealed that subjects with high cortisol/low noradrenaline had higher PAI-1 than subjects with low cortisol/high noradrenaline ( P =0.038). Subjects with high adrenaline/high noradrenaline had higher D-dimer than subjects with high adrenaline/low noradrenaline ( P =0.029), low adrenaline/high noradrenaline ( P =0.022) and low adrenaline/low noradrenaline (not significant). When covariance for several confounders of haemostatic function was determined, the main effect of adrenaline on fibrinogen and the interaction between adrenaline and noradrenaline for D-dimer maintained significance. Although overnight SNS hyperactivity was associated independently with morning hypercoagulability, the relationship between the activity of HPAA and haemostasis was mediated by traditional cardiovascular risk factors.

The aim of the present study was to quantify β 2 -adrenoceptor protein content in adipose tissue during fasting, and to study the relationships between β 2 -adrenoceptor protein and mRNA levels and changes in metabolites related to lipolysis. Groups of male subjects with a body mass index of <25kg/m 2 or >30kg/m 2 fasted for 60h. Abdominal subcutaneous fat biopsies were analysed for receptor mRNA levels by reverse transcription–PCR–HPLC. The β 2 -adrenoceptor protein concentration was measured by Western blotting using fluorescence laser scanning for detection. The β 2 -adrenoceptor protein concentration per cell (on a DNA basis) was higher in obese subjects ( P <0.03). There were highly significant relationships between β 2 -adrenoceptor protein concentration and both body mass index and waist/hip ratio ( P <0.001 for both). Furthermore, there was an inverse relationship between the receptor protein concentration and the serum β-hydroxybutyrate level during fasting ( P <0.005). β 2 -Adrenoceptor protein levels decreased in both groups during fasting, to a similar degree. Basal β 2 -adrenoceptor mRNA levels were similar in the two groups, but there was a smaller increase in the obese group during fasting ( P <0.03). The increased β 2 -adrenoceptor protein level in obese subjects is likely to be related to the greater plasma membrane area of their adipocytes. The decrease during fasting may be due to increased binding of noradrenaline and subsequent internalization and degradation of the receptor. Elevated levels of less responsive β 2 -adrenoceptor protein in obese subjects may contribute to the development of obesity.

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. Twenty middle-aged men with untreated sustained essential hypertension for more than 5 years and 19 comparable normotensive controls were investigated. Both groups were derived from The Oslo Study, where they had served as control hypertensive and normotensive subjects. 2. Supine venous and arterial plasma catecholamines were increased in the hypertensive subjects compared with the normotensive subjects. The mean arterial—venous difference for adrenaline in the hypertensive (0.45 ± se 0.08 nmol/l) was increased compared with the normotensive group (0.27 ± 0.03 nmol/l, P < 0.05). Similarly, the venous-arterial difference for noradrenaline was increased in the hypertensive (0.29 ± 0.13 nmol/l, P < 0.05) compared with the normotensive group (−0.07 ± 0.11 nmol/l). 3. The results are consistent with an increased release of adrenaline from the adrenal medulla and noradrenaline from the peripheral vascular beds (forearm) in essential hypertension. The increased arterial-venous difference for adrenaline in the hypertensive group also suggests an increased uptake of adrenaline in the peripheral vascular beds.

1. Angiotensin II (AII) antagonists, namely Sar 1 ,Ile 8 -AII, Sar 1 ,Ala 8 -AII and Sar 1 ,Thr 8 -AII, were administered daily for 4 weeks to normotensive rats to study their effect on cardiac hypertrophy. 2. None of the antagonists altered blood pressure significantly but Sar 1 ,Ile 8 -AII and Sar 1 ,Ala 8 -AII produced a significant increase in heart weight, as compared with untreated age-matched control rats. Administration of Sar 1 ,Thr 8 -AII did not produce cardiac hypertrophy. 3. A significant increase in catecholamine concentration was observed in the ventricles of rats treated with Sar 1 ,Ile 8 -AII and Sar 1 ,Ala 8 -AII but no change was found in the group treated with the Sar 1 ,Thr 8 -AII analogue. The production of cardiac hypertrophy by Sar 1 ,Ile 8 -AII was prevented by bilateral adrenalectomy, suggesting an important role for catecholamines in modulating cardiac hypertrophy.

1. The activities of the enzymes involved in catecholamine synthesis, tyrosine hydroxylase, aromatic amino acid decarboxylase and dopamine β-hydroxylase, were markedly enhanced in homogenates of phaeochromocytoma compared with human adrenal medulla homogenates measured under optimum substrate concentrations. 2. It was demonstrated in fresh tumour slices that the rate of formation of dopamine (3,4-dihydroxyphenethylamine) from tyrosine was much slower than the rate of formation of dopamine from dopa (3,4-dihydroxyphenylalanine) (suggesting that tyrosine hydroxylase was the rate-limiting enzyme in noradrenaline synthesis in phaeochromocytoma) and that the tyrosine hydroxylation step was still susceptible to end-product inhibition by catecholamines. 3. It is suggested that catecholamine overproduction in phaeochromocytoma is due to the increased activities of catecholamine synthetic enzymes rather than to an insensitivity of tyrosine hydroxylase to end-product inhibition. 4. The activities of the enzymes involved in catecholamine catabolism, monoamine oxidase and perhaps catecholamine O -methyltransferase, were reduced in phaeochromocytoma. This finding provides a biochemical basis for the previous published observations of nonexocytotic release of catecholamines in these tumours. Thus excess amounts of newly synthesized noradrenaline which cannot be stored in the filled catecholamine storage vesicles may not be degraded owing to the reduced monoamine oxidase activity and could diffuse from the phaeochromocytoma into the circulation.

1. The interactions of dopamine, reserpine and methyldopa on blood pressure of normal subjects and of those with essential hypertension were examined. 2. When biosynthesis of noradrenaline from dopamine was blocked by reserpine, dopamine induced a prominent depressor effect in essential hypertension. 3. The long-term treatment with methyldopa induced a marked potentiation of the pressor action of domapine in hypertension, although no significant pressor response was found in normal subjects. 4. It is suggested that methylnoradrenaline may accumulate in peripheral nerve endings of patients with essential hypertension in comparison with normal subjects, and this accumulated methylnoradrenaline potentiates the pressor response to dopamine in essential hypertension.

1. Changes in plasma concentrations of catecholamines and Cortisol were measured before and after static exercise performed by the subject pushing with both legs against a strain-gauge bar. No marked changes in plasma catecholamine were observed but plasma Cortisol increased after the subject pushed for 3 min at 50% of maximum force. 2. Holding a 20 kg weight for 5 min in one hand caused a rise in plasma Cortisol and in plasma ACTH but no changes in growth hormone were observed.