Open AccessIn Vitro and In Vivo Inhibition of Human and Primate Renin by a New Potent Renin Inhibitor
Author(s) -
M. De Claviere,
Catherine Cazaubon,
Colette Lacour,
Dino Nisato,
J. P. Gagnol,
Geneviéve Evin,
Pierre Corvol
Publication year - 1985
Publication title -
journal of cardiovascular pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.762
H-Index - 100
eISSN - 1533-4023
pISSN - 0160-2446
DOI - 10.1097/00005344-198507004-00012
Subject(s) - renin–angiotensin system , renin inhibitor , in vivo , in vitro , chemistry , plasma renin activity , endocrinology , pharmacology , medicine , blood pressure , pepstatin , biology , biochemistry , enzyme , protease , microbiology and biotechnology
A new potent renin inhibitor, Iva-Phe-Nle-Sta-Ala-Sta-OH (SR 42128), and its arginine salt (SR 42128A) have been synthesized. This compound had a concentration required to displace 50% of ligand binding of 2.8 X 10(-8) M toward human plasma renin at pH 7.4 and was 2,000 times more potent than pepstatin. All primate renins tested were inhibited within the same order of magnitude whereas other animal renins were much less inhibited. The effect in vivo of SR 42128A was studied in sodium-depleted conscious monkeys. A single dose of SR 42128A produced a dose-dependent blood pressure decrease as well as a dose-dependent inhibition of plasma renin activity (PRA). Blood pressure was still significantly lowered 3 h after a single administration of 3 or 10 mg/kg whereas PRA was still completely inhibited. SR 42128 is a potent and long-acting tool for studying the role of the renin angiotensin system in primates and humans.