Clinical science and molecular medicine. Supplement最新文献

1. Active and acid-activable inactive renin were measured in renal venous and arterial plasma of 18 patients with essential hypertension (EHT) and 19 patients with renovascular hypertension (RVHT). In seven patients with EHT and in 11 patients with RVHT measurements were made before and 25-35 min after an intravenous injection of 300 mg of diazoxide. 2. Under basal conditions the renal vein to artery ratios for active and inactive renin in EHT ranged from 0.71 to 1.96 and from 0.68 to 1.44 respectively. In 14 patients with RVHT the renal vein to artery ratio for active renin on the affected side was above the range found in EHT and in six of them the renal vein to artery ratio for inactive renin was also elevated. 3. The diazoxide-induced release of active renin from kidneys, which had a stenotic artery but were not seriously contracted, was associated with a fall of the renal vein to artery ratio for inactive renin to a value below 1.00. 4. The results indicate that changes in the release of active and inactive renin do not always run in parallel. The findings are compatible with the hypothesis that circulating inactive renin can be activated in the kidney.

1. The capacity of various tissues of the porcine kidney to convert [1-14C]arachidonic acid into radiolabelled prostaglandins was studied. 2. Only after removal from the cortical matrix, were renal blood vessels able to convert arachidonic acid into prostaglandins (primarily prostacyclin). In contrast, convoluted tubules showed a low capacity to metabolize arachidonic acid. 3. The failure to demonstrate prostaglandin synthesis by renal cortical slices is related to the presence of an inhibitor of cyclo-oxygenase. Thus the addition of renal cortical incubate to isolated vascular tissues and ram seminal vesicles inhibited their ability to synthesize prostaglandins. 4. Slices of renal medulla metabolized arachidonic acid primarily to prostaglandin F2alpha; lesser amounts of prostaglandin E2 and prostacyclin were generated. 5. The large capacity of the renal vasculature to generate prostacyclin is consistent with an important role for this prostaglandin in regulation of renin release and renal haemodynamics.

1. A highly significant inverse relationship was found between blood pressure in untreated hypertensive subjects in late pregnancy and birth weight. 2. Reversal of this intrauterine growth retardation was achieved in 19 patients by treatment of hypertension with oxprenolol. 3. No adverse effects from oxprenolol were found in the patients or in their babies.

1. The effects of oral administration of 4.5 mg of prazosin/day on blood pressure and on plasma renin activity were assessed in patients with essential hypertension and in healthy normotensive volunteer subjects. 2. Mean blood pressure in the hypertensive group fell significantly within 2 weeks of treatment, whereas heart rate was little affected. None of the parameters measured in the normotensive subjects during treatment with prazosin revealed significant changes. 3. Sub-classification of the hypertensive patients into low-, normal- and high-renin categories revealed significant decreases of renin in all six patients with high renin- and in four out of 12 patients with normal renin- but not in the two patients with low renin-essential hypertension. 4. The results indicate the prazosin exerts its hypotensive action and suppresses plasma renin activity particularly in patients with high renin-essential hypertension. These may be considered to have increased sympathetic drive. 5. Conceivably, the blood pressure-lowering effect of prazosin is affected by peripheral vasodilatation and also by a decreased venous return to the heart.

1. Vascular reactivity was studied in Tyrode solution perfused kidneys from young (7 weeks) and mature (4-6 months) spontaneously hypertensive rats (SH rats). 2. The response to nerve stimulation was greater in the kidneys from young SH rats than in those from young control rats, both in control solution and after inhibition of the disposition of noradrenaline; both groups exhibited the same sensitivity to noradrenaline, angiotensin II and barium chloride. 3. The response to nerve stimulation was normal in kidneys from mature SH rats, but responses to noradrenaline, angiotensin II and barium chloride were greater than the control. 4. Cocaine potentiated the response to nerve stimulation more in the kidneys from mature SH rats than in those from the control rats. 5. The results suggest that renal sympathetic nerves release more noradrenaline than normal in the young SH rats, which could be an important factor in causing hypertension. 6. In the established phase of spontaneous hypertension the vascular reactivity to exogenous agonists is increased, probably as a consequence of high blood pressure; the more efficient neuronal uptake causes normalization of the response to sympathetic nerve stimulation.

1. 20 subjects with uncomplicated essential hypertension were studied, 10 of whom were on propranolol treatment. Several blood samples for determination of total and active renin were drawn simultaneously from the renal artery and vein after angiographic studies. 2. In all patients renal blood flow was measured by Hippuran-clearance at the time of blood sampling. Intrarenal blood flow was assessed by xenon-washout. 3. The results indicate that under basal conditions renin is secreted mainly in the active form, although secretion of inactive renin does occur. During propranolol treatment there is a tendency for secretion of active renin to be reduced.

1. The protease inhibitors Trasylol and soyabean trypsin inhibitor prevented the activation of plasma inactive renin by acid. 2. N-Ethylmaleimide inhibited acid-activation to some extent but o-phenathroline had no effect. 3. Acid-activation of the inactive renin in human plasma is mediated by a serine protease.

1. Haemodynamic responses to diazoxide (300 mg intravenously) were studied in 15 hypertensive patients before and after chronic beta-adrenoreceptor blockade by 320 mg of propranolol daily. After diazoxide alone, mean arterial pressure and total peripheral resistance were lowered by 24 +/- 3 and 35 +/- 5% (mean +/- SEM) respectively. Cardiac output and heart rate rose by 25 +/- 9 and 21 +/- 3%. During beta-adrenoreceptor blockade, the percentage changes of mean arterial pressure, heart rate, cardiac output and total peripheral resistance after vasodilatation were not significantly different from those after diazoxide alone. 2. Atropine, 0.04 mg/kg body weight, was given to 12 hypertensive patients chronically treated with beta-adrenoreceptor blockade, before acute vasodilatation by diazoxide. Diazoxide caused no increase in heart rate after combined beta-adrenoreceptor and parasympathetic blockade. However, cardiac output rose by 14 +/- 5%. 3. We conclude that withdrawal of parasympathetic tone is an important determinant of circulatory homeostasis after acute vasodilatation during beta-adrenoreceptor blockade.

1. Synthesis of several pepstatin A derivatives was performed with the aim of increasing water solubility without altering the capacity to inhibit the renin-angiotensinogen reaction. 2. Pepstatinyl-arginine-O-methyl ester was studied in vitro and in vivo and compared with pepstatin A and with the arginine salt of pepstatin A. 3. This compound inhibited in vitro the reaction between purified hog renin and the synthetic renin N-acetyl-tetradecapeptide or the natural rat renin substrate. The inhibitory constant was of the same order of magnitude as that of pepstatin A. 4. In renal hypertensive rats, the bolus injection of pepstatinyl-arginine-O-methyl-ester or of the arginine salt of pepstatin decreased blood pressure to the same extent as a bolus injection of Sar1, Ala8-angiotensin II.