Antihypertensive profile of the angiotensin-converting enzyme inhibitors CI-906 and CI-907.
CI-906 and CI-907, new orally active nonsulfhydryl angiotensin-converting enzyme inhibitors, were examined for antihypertensive effects in unanesthetized hypertensive rats and dogs. In two-kidney, one-clip Goldblatt hypertensive rats, single oral daily doses (0.03-30 mg/kg) produced dose-dependent decreases in blood pressure; a single 3 mg/kg oral dose lowered blood pressure to normotensive levels. In spontaneously hypertensive rats, 30 mg/(kg X day) orally administered for 5 consecutive days achieved the same blood pressure decrease as that obtained on the first day in the renal hypertensive rats. In diuretic-pretreated renal hypertensive dogs, a 10 mg/kg oral dose decreased blood pressure by 25%. No adverse side effects were observed with CI-906 and CI-907 in any of the conscious animals. These studies indicate that CI-906 and CI-907 are potent, orally active antihypertensive agents without any apparent limiting side effects.
D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D000959:Antihypertensive Agents; D002216:Captopril / Q000627:therapeutic use; D004151:Dipeptides / Q000627:therapeutic use; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004656:Enalapril; D005260:Female; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D006977:Hypertension, Renal / Q000188:drug therapy; D006978:Hypertension, Renovascular / Q000188:drug therapy; D007211:Indoles / Q000627:therapeutic use*; D007546:Isoquinolines / Q000627:therapeutic use*; D007700:Kinetics; D008297:Male; D000077583:Quinapril; D051381:Rats; D011919:Rats, Inbred Strains; D012084:Renin-Angiotensin System; D044005:Tetrahydroisoquinolines
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D004151:Dipeptides; D007211:Indoles; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D004656:Enalapril; D002216:Captopril; C038812:Indolapril; D000077583:Quinapril