Antihypertensive activity of captopril (SQ 14,225), an orally active inhibitor of angiotensin converting enzyme in conscious two-kidney perinephritic hypertensive dogs.

Conscious dogs made hypertensive by wrapping both kidneys with cellophane were treated daily with a single dose of captopril (31 mg/kg p.o.), an inhibitor of the angiotensin converting enzyme, or with placebo (lactose, 31 mg/kg p.o.) for a period of 13 weeks. Blood pressures were recorded indirectly from a forepaw by using a Roche ultrasonic pressure transducer (Arteriosonde). Treatment with captopril resulted in decreases in blood pressure (25-30 mm Hg) that were maximal at 3 to 6 hr with no associated changes in heart rate. The captopril-induced hypotensive effect was maintained throughout the 13-week treatment period, and after the termination of captopril dosing, pressure rose slowly over the next 72 hr to a level not significantly different from placebo-treated dogs. Plasma renin activity (PRA) in the hypertensive dogs at the time treatment was initiated was not different from the same animals when they were normotensive. In captopril-treated animals, PRA increased 3- to 4-fold after each dose of the drug was given, reaching a maximum at 3 to 6 hr, a time corresponding to the maximal blood pressure decrease. PRA gradually declined but did not reach control levels before the next dose of captopril was administered. In animals treated with placebo, PRA remained at levels not significantly different from normotensive dogs during the entire treatment period. After termination of captopril administration, PRA slowly returned to pretreatment levels; the return of PRA paralleled the recovery of blood pressure. The results indicate that captopril is effective in reducing blood pressure for an extended period of time in a hypertensive model in which the level of activity of the renin angiotensin system is not elevated.