Michel B. Vallotton

Reversible Acute Renal Failure from Combined Triamterene and Indomethacin: A Study in Healthy Subjects

As part of a study on the interaction between diuretics and renal prostaglandins, four healthy medical students receiving indomethacin for 8 days were also given triamterene for 3 days. Whereas renal function was initially normal in all four subjects, creatinine clearance decreased in two by 62% and 72% after concomitant administration of the two drugs, and was only restored to normal after 4 weeks. In control periods when triamterene or indomethacin was given alone renal function was preserved in all subjects. Urinary prostaglandin E2 was stimulated by triamterene and inhibited by indomethacin in all four subjects; both changes were more marked in the two sensitive subjects. Thus prostaglandin inhibition by indomethacin may unmask triamterene toxicity and contribute to the pathogenesis of the renal failure observed in sensitive subjects. As alternative therapy is readily available, avoidance of this potentially nephrotoxic association is recommended.

Kinetics of the reaction of human renin with natural substrates and tetradecapeptide substrate

Abstract 1. 1. The reaction of purified human renin (EC 3.4.4.15) was studies with four substrate, two homologous (unpurified and partially purified plasma human substrate), one heterologous (hog substrate), and one of synthetic origin (tetradecapeptide substrate) representing the N-terminal sequence of the other three substrates. 2. 2. The activity of renin was determined by specifically measuring with a radioimmunoassay the formation of angiotensin I, the direct product of the enzymatic reaction. The effects of pH, ionic strength, temeperature and substrate concentraion, were examined for each substrate, and the respective optimum pH, activation energies, maximal velocities and Michaelis constants were determined. 3. 3. Human renin presented with the tetradecapeptide substrates a 100-times faster reactivity than with the other substrates, but accompanied by a 10-times lower affinity. With human substrate a physiological plasma concentration, a first-order reaction was obtained at optimum pH (5.5) but which tended to a zero-order at physiological pH. This indicates that whereas the substrate is a rate-limiting factor in the in vitro conditions of most methods of measurement of renin activity, it appears to be in a sufficient amount for the in vivo reaction. 4. 4. Two factors known to inhibit in vivo renin secretion, angiotensin II and potassium ion, were demonstrated as well as angiotensin I not to influence in vitro the activity of human renin.

Nifedipine in Pheochromocytoma

Excerpt To the editor: The calcium antagonist nifedipine has been shown to suppress symptoms in two patients with pheochromocytoma (1, 2) while decreasing urinary norepinephrine and vanillylmandeli...

Epithelial liver hamartoma, systemic arterial hypertension and renin hypersecretion.

The case of a 14-year old girl presenting with headaches, severe progressive hypertension and high plasma renin levels, in whom a voluminous epithelial liver hamartoma or adenoma was discovered at surgery is documented. The morphological characteristics of the hamartomatous abnormality are described and evidences are put forward which would suggest that the liver lesion might have been the site of the abnormal renin production which was responsible for the systemic arterial hypertension.

Influence of pH on human renin activity with different substrates: Role of substrate denaturation

Abstract 1. 1.|The activity of human renin (EC 3.4.4.15) was studied with four different substrates, two of human origin, one of hog origin and one synthetic substrate. 2. 2.|The formation of angiotensin I was determined by radioimmunoassay. 3. 3.|A different optimum pH was obtained with each substrate: pH 5.5 with human substrate in plasma, pH 6 with partially purified human substrate, pH 7.5 with hog substrate and pH 4.5 with tetradecapeptide substrate, i.e. the N-terminal sequence of the three latter substrates. 4. 4.|These different optima in the presence of the same enzyme could be due to a direct effect of pH on the substrate. Such an effect was demonstrated with human substrate by its progressive acidification before incubation at its optimum pH with human renin. Below pH 5 the acidification produced an irreversible inactivation of natural or partially purified human substrate, whereas hog substrate, tetradecapeptide substrate and human renin offered a better resistance to acid pH. 5. 5.|When compared to the low optimum pH obtained with tetradecapeptide substrate, the higher optimum of the pH curve of human renin activity with human substrate is thus attributed to an acid denaturation of this substrate.

Primary aldosteronism with bilateral adrenal adenomas

An unusual case of primary aldosteronism with bilateral single adenomas is reported. The two tumors were revealed by computerized axial tomography and subsequently confirmed by surgical exploration. Spironolactone therapy prior to the operation induced the formation of spironolactone bodies in only one of the two adenomas. As it has been postulated that these cytoplasmic inclusions may reflect the activity of the adenomatous cells, the presence of the bodies in a single adenoma would indicate a unilateral source of the hyperaldosteronism. Thus, the existence of spironolactone bodies could corroborate the data of functional localizing tests more closely than the morphological findings of computerized tomography.

Action of calcitonin gene-related peptide on rat aortic smooth muscle

The effects of rat calcitonin gene-related peptide (CGRP) on superfused rat aortic smooth muscle cells in cell culture were investigated. Exposure of the cells for 10 min to CGRP (10(-7) M), with or without pretreatment with pertussis toxin, stimulated the release of cyclic AMP but not of prostacyclin, as judged by radioimmunoassay of its stable metabolite, 6-keto-PGF1 alpha. Pretreatment of the cells with pertussis toxin did not alter the response to CGRP. The direct action of CGRP on smooth muscle cells and on the CGRP-induced formation of cyclic AMP did not appear to depend on the production of prostacyclin in these vascular smooth muscle cells.

Specificity of antibodies to arginine-vasopressin raised with succinylated poly-l-lysine as carrier

Des anticorps dirigés contre larginine-vasopressine ont été obtenus chez le lapin après immunisation avec un copolymère ramifié de poly-l-lysine succinylée et darginine-vasopressine. La spécificité de ces anticorps est remarquable puisque non seulement lon nobserve pratiquement pas de réaction croisée avec loxytocine, mais en plus leur affinité pour la lysine-vasopressine est environ 35 fois plus faible que pour larginine-vasopressine.