Angiotensin converting enzyme inhibitors and atherosclerosis

Abstract

This study was designed to evaluate possible antiatherosclerotic effects of angiotensin converting enzyme inhibitors in mini-pigs. Experimental hypercholesterolemia and atherosclerosis were produced in mini-pigs of the Göttingen strain by adding 11% egg yolk and 1% cholesterol to the diet for 52 weeks. The animals were divided into three groups. One group was fed the atherogenic diet alone and served as control. The second group was treated with captopril in a dose of 80 mg/kg/day added to the atherogenic diet on an individual basis. The third group was treated with fosinopril in a dose of 8 mg/kg/day. Both drugs produced a significant reduction in serum ACE activity associated with a reactive rise in plasma renin activity and a slight fall in serum aldosterone concentration. The drug treatment had only minor effects on plasma lipids. The aorta and the carotid and coronary arteries were examined for atherosclerotic lesions. Atherosclerotic plaques developed in the abdominal aorta whereas fatty streaks were present in the thoracic aorta and the coronary arteries. Both drugs significantly reduced the percent visible atherosclerosis in the abdominal aorta. Furthermore, the accumulation of cholesterol in the thoracic and abdominal aorta was significantly reduced. The effect of captopril and fosinopril on endothelium-dependent relaxation of iliac arteries was examined. After addition of 3 x 10(-7) M acetylcholine strips from basal diet fed mini pigs showed a remaining tension of 7.0% +/- 7.1 (p < 0.05 compared to cholesterol-high diet), cholesterol-high diet 36.4% +/- 10.2, captopril 16.9% +/- 4.9 (p < 0.01) and fosinopril 31.7% +/- 4.6 (n.s.). It is concluded that the ACE inhibitors captopril and fosinopril inhibited the development of atherosclerosis in hypercholesterolemic mini-pigs.