indolapril-hydrochloride and Hypertension

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.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Captopril; Dipeptides; Disease Models, Animal; Dogs; Dose-Response Relationship, Drug; Enalapril; Female; Hypertension; Hypertension, Renal; Hypertension, Renovascular; Indoles; Isoquinolines; Kinetics; Male; Quinapril; Rats; Rats, Inbred Strains; Renin-Angiotensin System; Tetrahydroisoquinolines