[Incidence of beta-blockers on plasma renin activity. Present status].
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Biomedical subjects
Publications and source records attributed to J Ménard.
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Six patients with permanent hypertension with renal artery stenosis were treated by conservative reparative surgery appart from one of them (unilateral nephrectomy) and were all seen again at the 8th month at the earliest in the absence of any anti-hypertensive therapy. Study of the renin-angiotensin system carried out on a normal sodium diet, after stopping all anti-hypertensive treatment for at least 15 days, was combined with the anti-hypertensive response under the influence of a beta-blocker. There were two types of response pre-operatively: firstly, with beta-blockers alone a normal blood pressure which remained normal postoperatively; the second group of patients remained hypertensive, requiring the addition of diuretics, and remained hypertensive after surgery. This response, although non-specific, would appear to represent an important element in assessing the curability of reno-vascular hypertension.
The cardiac output of 11 patients was measured by a method of dilution of a short-life radio-isotope, and compared with measurements obtained simultaneously by a dye dilution technique. After sudden intravenous injection of siderophilin (transferrin) labelled by Indium 113 m, the precoridal radioactivity was measured by a single panel detector probe. In 9 patients these measurements were carried out twice with a 15 minute interval. The correlation coefficient between the two methods was 0.884 for 20 measurements, and 0.939 for the first 11 measurements. The reproducibility of these measurements was comparable for the two techniques. The radio-isotope method of measuring cardiac output, which can be carried out at the bedside, is a simple, reliable and reproducible technique.
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A method has been set up to purify renin on a large scale by affinity chromatography using Pepstatin, a potent inhibitor of renin, as a ligand. Pepstatin was covalently coupled to Sepharose via six different spacer 'arms'. The Sepharose-hexamethylenediamino-Pepstatin appeared to be the better derivative for renin purification even at a concentration as low as 160 nmol of Pepstatin/ml of moist gel. Renin was extracted from 100 kg of hog kidneys and semi-purified by ammonium sulfate precipitations and chromatography on DEAE-cellulose. The active fraction (48.5 g of proteins) was applied on a 500-ml affinity column. Renin was eluted in the starting buffer containing 6 M urea. Renin was purified 120-fold by the affinity chromatography step with a 79% recovery. Physico-chemical characterization of highly purified renin was performed. Isoelectrofocusing on a pH gradient from 3 to 6 showed a major peak with an isoelectric point (pI) of 4.95 and a minor peak (pI = 4.70). Polyacrylamide gel electrophoresis, pH 7.8, at different gel concentrations, showed a single peak of renin activity which was found in the major protein band. Molecular size estimated on agarose-acrylamide gel filtration was 40 000. All these physical parameters were similar before and after purification.
Spirolactones (spironolactone, potassium canrenoate) may produce secundary sexual effects such as gynecomastia in man and menstrual disturbances in women. The mechanism of action of the antiandrogenic effects has been studied in man and rat. Acute i.v. injection of potassium canrenoate into man results in a decrease of plasma testosterone, without any change of gonadotropins. This decrease might be due to an impaired testicular steroidogenesis. On the other hand, spirolactones have an antiandrogenic effect at the target cells level. They do not modify the prostate 5alpha-reductase activity; however, they do inhibit the binding of androgens to their receptors. Thus the spirolactones interact with both biosynthesis and peripheral action of androgens.
Acebutolol, a new cardioselective beta-blocking agent, has been given for 5 days, at a daily dosage of 600 mg to 8 patients with mild essential hypertension. Plasma Renin Activity (PRA), Plasma aldosterone (PA), Aldosterone Metabolic Clearance Rate (AMCR), Aldosterone Secretion Rate (ASR) have been compared before and after treatment. Whatever is the daily sodium intake, acebutolol decreases PRA and does not change AMCR. Under a normal sodium diet, PA and ASR are unchanged, in spite of the fall in PRA. On the contrary, under a sodium free diet, the decrease in PRA is accompanied by a decrease in PA and ASR.
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The antihypertensive effect of acebutolol, a new cardioselective beta-blocking drug, is studied in 31 patients with mild essential hypertension. Administration of acebutolol (2,000 mg) in 48 hours produced a significant decrease in blood pressure, heart rate, plasma renin activity (P.R.A.) and an increase in systolic time intervals (pre-ejection period and isovolumetric contraction time). The blood pressure drop is highly correlated to the initial P.R.A. values, but is not related either to the initial heart rate, or to the systolic time intervals values.
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