In vitro and in vivo inhibition of human and primate renin by a new potent renin inhibitor: SR 42128.
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.
M
M
De Claviere
C
C
Cazaubon
C
C
Lacour
D
D
Nisato
J P
JP
Gagnol
G
G
Evin
P
P
Corvol
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002143:Callitrichinae; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008252:Macaca fascicularis; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D010215:Papio; D010436:Pepstatins / Q000494:pharmacology; D051381:Rats; D012083:Renin / Q000097:blood; D012964:Sodium / Q000502:physiology; D000092502:Renin Inhibitors
D009842:Oligopeptides; D010436:Pepstatins; D012083:Renin; D012964:Sodium; D000092502:Renin Inhibitors; C046599:SR 42128