Antiatherosclerotic effect of alacepril, an angiotensin-converting enzyme inhibitor, in monkeys fed a high-cholesterol diet.
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.
Miyazaki
M
M
Department of Pharmacology, Osaka Medical College, Takatsuki, Japan.
Takai
S
S
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000201:enzymology / Q000473:pathology; D001018:Aortic Diseases / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001798:Blood Proteins / Q000378:metabolism; D002216:Captopril / Q000031:analogs & derivatives* / Q000494:pharmacology; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D005500:Follow-Up Studies; D006339:Heart Rate / Q000187:drug effects; D008251:Macaca; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000187:drug effects / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D001798:Blood Proteins; D002791:Cholesterol, Dietary; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D002216:Captopril; D007703:Peptidyl-Dipeptidase A; C046835:alacepril