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Biomedical subjects

J Menard

Publications and source records attributed to J Menard.

At least 199 records · Page 11Linked to original sources

IgG versus albumin for measurement of plasma volume in normal and hypertensive men.

Labeled IgG was evaluated versus labeled albumin for measurement of plasma volume, to see whether it would give a smaller initial dilution volume (indicating a smaller premixing extravascular loss of label) and a smaller difference between initial dilution volume and dilution volume at time 10 min (indicating a negligible extravascular loss in the first 10 min after mixing). IgG was found to have a lower transcapillary escape rate than albumin (P less than 0.01) in eight normal volunteers and in eight hypertensive subjects, hypertension being associated with an increased transcapillary escape of both proteins. Despite this, the dilution volumes obtained were indistinguishable and the need for a correction through a retropolation procedure was the same with both proteins. Albumin and IgG dilution volumes were highly correlated in 21 subjects (r=0.977) so that use of labeled IgG is a proper alternative to use of labeled albumin for plasma volume determination. However, since IgG brings no consistent advantage, labeled albumin remains the best available tracer for that purpose.

Blood Pressure↗

Fluorimetric assay of renin.

A simple fluorimetric assay was set up to test renin within 2 h. N-acetyltetradecapeptide was synthesized and used as substrate. It was demonstrated that N-acetyl-angiotensin I and Leu-Val-Tyr-Ser were the two peptides obtained after hydrolysis by renin. Fluorescamine reaction reacted with the free NH2 of the tetrapeptide generated to induce a fluorimetric reaction detected at 395--405 nm. The Michaelis constant of the reaction was 1.87 . 10(-5) M. With this method as little as one milliGoldblatt Unit (mG.U.) of hog renin could be detected and the generation of tetrapeptide was linear with respect to the renin concentration up to 20 mG.U. The fluorimetric assay was applied to the detection of renin during its purification and to the characterization of renin inhibitors.

Animals↗

Plasma renin substrate sensitivity to oestrogens and oestrogen metabolism in cirrhosis.

Oestrogen stimulation of plasma renin substrate (PRS) was studied in men with alcoholic cirrhosis. PRS values, before and 1, 2, 4 and 6 days after a single oral administration of 100 microgram of an oestrogen derivative, 11beta-methoxy-17-ethynyl-1,3,5(10)-estratriene-3,17beta-diol (Moxestrol), were measured by radioimmunoassay of generated angiotensin I in five men with normal liver function and five men with alcoholic cirrhosis. Basal PRS was 0.93 +/- 0.22 nmol/ml (mean +/- 1 SD) in the normal men and significantly lower (P less than 0.01) in the men with cirrhosis (0.33 +/- 0.14 nmol/ml). Two days after administration of Moxestrol, PRS rose significantly but transiently (P less than 0.05) to 1.41 +/- 0.42 nmol/ml in the normal men and to 0.47 +/- 0.15 in the cirrhotic men, the relative increase (approximately 50%) being similar in both groups. A study of the plasma kinetics and urinary excretion of Moxestrol was also performed to evaluate its metabolic clearance rate and absorption. Since the intestinal absorption of [14C] Moxestrol was not depressed in cirrhotic men, the low PRS values recorded are probably the consequence of hepatocyte dysfunction.

Adult↗

Aldosterone metabolism in isolated perfused rat kidney.

The renal metabolism and handling of [1,2-3H]aldosterone ([3H]A) was studied using isolated perfused rat kidney under different perfusion conditions. The metabolite production rate (MPR) and the urinary excretion of [3H]A together with its radiometabolites (UV/P3H) were studied. Among the formed metabolites, no acid-labile conjugate of aldosterone (ALC) was detected. The MPR was not altered in studies using nonfiltering kidney, a result that suggests that the majority of metabolites were formed without requirement of the process of glomerular filtration and tubular uptake of the hormone. High perfusion pressure (high PP) resulted in a striking increase in whole metabolic clearance rate of aldosterone (MCR[3H]A) due mostly to an enhanced urinary excretion of intact aldosterone and, to a lesser degree, to a significant increase in MPR. Factors determining the excretion rate of [3H]A and its metabolites were than investigated under administration of diuretics. Mannitol (44 mM) induced a marked increase in urine volume (UV) accompanied by a significant UV/P3H increase. Meanwhile, 0.1 mM furosemide resulted in an increase only in UV, but not in UV/P3H. These results revealed the UV dependence of aldosterone excretion in certain diuretic conditions.

Aldosterone↗

Soluble pepstatins: a new approach to blockade in vivo of the renin-angiotensin system.

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.

Animals↗

[The renin-angiotensin-aldosterone system in hypertensive patients. II. Diagnosis of primary hyperaldosteronism].

Twenty patients suffering from primary hyperaldosteronism were studied. Sixteen had a single adenoma of the adrenal and four had bilateral hyperplasia affecting both adrenals. Cases of primary hyperaldosteronism due to a tumour were characterised by a higher degree of hypermineralocorticism than was seen in the patients with hyperplasia. Plasma aldosterone, after acute volaemic expansion, did not fall below 13 ng/100 ml in the adenoma patients whilst it was lower in the case of hyperplasia. Adrenal phlebography is a useful tool in preoperative diagnosis.

Adenoma↗

Large scale purification of hog renin. Physicochemical characterization.

Renin was purified from 47 kg of hog kidney to produce enough enzyme for enzymatic and physicochemical characterization. The procedure included extraction at pH 3.5 in the presence of protease inhibitors, two ammonium sulfate precipitations, ion exchange chromatography on Sepharose-hexamethylenediamino-pepstatin gel, gel filtration, and isoelectric focusing. Renin, 2.3 mg, with a specific activity of 1,100 GU/mg of protein was obtained with about 70,000-fold purification and 16% overall recovery. The purity criteria were: (1) a single band on sodium dodecyl sulfate (SDS)-gel electrophoresis, (2) same retardation factor on polyacrylamide gel electrophoresis for renin activity, protein and glycoprotein coloration. Renin was characterized by its stability at--20 degrees C, pH 6.5; its molecular weight on SDS-gel electrophoresis, 36,800; its relative mobility on polyacrylamide gel electrophoresis at pH 7.8; its isoelectric point, 5.15; its amino acid composition, which revealed that renin is a glycoprotein; and its Michaelis constant on tetradecapeptide substrate at pH 6.6, Km = 7.7 X 10(-6) M.

Amino Acids↗

Effect of acute potassium loading on plasma renin and on urinary aldosterone in rats.

The disposition of aldosterone radiometabolites in rats has been studied following iv [3H]aldosterone administration. Of injected [3H]-aldosterone, 0.31% is recovered in 24 h urine as free aldosterone and 0.08% as acid-labile conjugate. A simple, sensitive and reliable radioimmunoassay of free aldosterone has been developed and the effect of acute oral potassium loading (171, 513 or 769 mueq of KCl/100 g body weight) on 4 h aldosterone excretion, plasma renin concentration and sodium and potassium balance has been investigated. There was a positive correlation between log urinary aldosterone and potassium load (r = 0.92, P less than 0.001). Potassium induced a natriuresis which was correlated directly with the dose of potassium administered (r = 0.89, P less than 0.001). Ptasssium loading also increased plasma renin concentration which was correlated with the sodium excretion rate (r = 0.64, P less than 0.01). Prevention of a negative sodium balance during the 769 mueq potassium load was obtained by administration of 513 mueq sodium. In this experiment, plasma renin concentration increased little, whereas the aldosterone excretion rate was as high as during the 769 mueq potassium load without sodium addition.

Aldosterone↗

Influence of beta-blockade on aldosterone metabolism under normal and low sodium diet in man.

During a five days administration, Propranolol (80 mg daily) or Acebutolol (600 mg daily) decreased significantly plasma renin activity in 14 mild essential hypertensive patients under a normal (8 patients) or low sodium (6 patients) diet. Plasma aldosterone and aldosterone secretion rate were significantly lowered by treatment under the low sodium diet, but unchanged during the normal sodium diet. In the latter, the dissociation observed between renin and aldosterone did not involve a change in aldosterone metabolic clearance rate or in plasma potassium. The decrease in plasma aldosterone was significantly correlated to the initial renin activity. These results demonstrate that the inhibitory effect of two different betablocking agents on renin release is not related to their cardio-selectivity and is independent of sodium balance. The influence of the renin decrease on aldosterone is dependent on sodium balance and on the initial state of the renin angiotensin system.

Acebutolol↗

Rapid identification of patients with essential hypertension sensitive to acebutolol (a new cardioselective beta-blocker).

Acebutolol, a new cardioselective beta-blocking agent, was administered for 48 hours to 44 patients with essential hypertension at a total dosage of 2.0 g (2,000 mg). The slowing down of their pulse rate and the decrease in blood pressure were highly significant, whereas eight subjects treated with placebos had no change in either the pulse rate or blood pressure. Plasma renin activity decreased from 2.26 +/- 2.11 ng/ml/hour to 0.87 +/- 1.04 ng/ml/hour. The decrease in blood pressure was correlated with the initial plasma renin activity and with the decrease in plasma renin activity. These results demonstrate that a rapid decrease in blood pressure can be obtained in patients with essential hypertension treated with acebutolol and that the decrease in blood pressure is related to the initial state of the renin-angiotensin system.

Acebutolol↗

Methodologic problems in plasma renin activity measurements.

The influence of pH and angiotensinase inhibitors on the in vitro generation of angiotensin I during PRA measurements has been investigated. PRA values obtained at pH 5.7 are higher than those obtained at pH 7.4. At pH 5.7, values obtained using diisopropylfluorophosphate (DRP 9 mM) as an angiotensinase inhibitor are higher than values obtained with a mixture of dimercaprol (BAL, 1.6 mM) and hydroxyquinoline (8-OHQ, 3 to 4 mM). Since the two methods for inhibiting angiotensinase are completely and equally efficient, it is suggested that these inhibitors might interfere with the renin angiotensinogen reaction. Significant correlations are observed between the PRA values obtained by the different methods which have been studied. Using an incubation pH of 5.7, and BAL and 8-OH quinoline as angiotensinase inhibitors, the distribution of PRA values in a population of 124 hospitalized hypertensive patients ingesting a normal sodium diet had been studied, and it has been demonstrated that the sensitivity of this method of measurement can detect small changes in PRA in patients with low renin activity.

Adenoma↗