Antiatherosclerotic Effect of Alacepril, an Angiotensin-Converting Enzyme Inhibitor, in Monkeys Fed a High-Cholesterol Diet.

Abstract

We investigated the effects of 6 months' treatment with the angiotensin-converting enzyme (ACE) inhibitor alacepril, given in low (100 mg/kg/d, p.o.) and high (200 mg/kg/d, p.o.) doses, on the development of atherosclerotic lesions in the aorta of monkeys fed a high-cholesterol diet for 6 mo. Mean blood pressures in the normal-diet group, high-cholesterol-diet group, and high-cholesterol-diet group treated with a low dose of alacepril were very similar, while that in the high-cholesterol-diet group treated with a high dose of alacepril was significantly reduced. The level of low-density lipoprotein in the high-cholesterol-diet group was significantly higher than that in the normal-diet group, and the levels in the alacepril groups were significantly lower than those in the high-cholesterol-diet group. Atherosclerotic lesions in the normal- and high-cholesterol-diet groups were 13.2 +/- 0.34% and 64.1 +/- 10.48%, respectively, and those in the groups treated with low and high doses of alacepril were 32.3 +/- 13.2% and 16.0 +/- 1.57%, respectively. Angiotensin-converting enzyme (ACE) activity in the thoracic aorta in the high-cholesterol-diet group was significantly higher than that in the normal-diet group, and the ACE activities in the alacepril groups were lower than that in the high-cholesterol-diet group. We conclude that alacepril prevents the development of atherosclerosis by reducing vascular ACE activity in monkeys given a high-cholesterol diet.