Continuous versus intermittent angiotensin converting enzyme inhibition in renal hypertensive rats. Hypertension

Converting enzyme inhibitors impair renal function of the kidney beyond a stenosis of the renal artery in humans and induce histologlcal lesions in the clipped kidney of renal hypertensive rats. In two-kidney, one clip hypertensive rats, we compared the time course and magnitude of the biochemical effects of angiotensin converting enzyme inhibition on the plasma renin-angiotensin system, cardiac hypertrophy, renal lesions, and 24-hour blood pressure decrease induced by either intermittent angiotensin converting enzyme inhibition administration (benazepril PO, 10 mg/kg once a day, n=93) or continuous adminis-tration (benazeprilat, 3 mg/kg per day via osmotic pumps, n=92). Control rats (n=91) received the drug vehicle intermittently or continuously. Mortality was significantly reduced by both intermittent (n=3/93) and continuous (n=3/92) inhibition compared with controls (n=18/91) (P<.001). Changes in the plasma renin-angiotensin system and blood pressure were parallel. A continuous suppression of the activity of the plasma renin-angiotensin system was associated with a 24-hour decrease in blood pressure with continuous inhibition, whereas intermittent inhibition induced a similar fall in blood pressure only for the first hours after gavage. Heart weight (5.12±0.12, 3.98±0.09, 4_32±0.12 g/kg in controls [n=8], continuous inhibition [n=18], and intermittent inhibition [n=18], respectively) was significantly reduced to the same extent by both treatments (P<.0001), and clipped kidney weight (3.28±0.11, 1.83±0.12