Captopril decreases accelerated atherosclerosis in hypertensive one kidney one clip rats fed cholesterol

Abstract

AbstractThe effect of captopril treatment on early atherosclerosis was determined in cholesterol‐fed rats with acute renovascular hypertension. Three groups were established: normotensive rats, hypertensive one kidney one clip (1K1C) rats, and 1K1C rats treated with 27 mg/kg/day of captopril. Animals in the 3 groups received chow containing 4% cholesterol and 1% cholic acid. Cholesterol feeding and drug treatment were started immediately following surgery, then after 1 or 2 weeks, mean arterial pressure, heart rate, and plasma lipids were measured; and the thoracic aorta was perfused with formalin. One or 2 weeks after surgery, mean arterial pressure increased by 17% to 22% in the 1K1C group compared to the normotensive animals. Captopril decreased blood pressure in the 1K1C rats by 22% to 25% compared to the hypertensive 1K1C group. In the 3 sets of rats, plasma cholesterol was similarly elevated from 109 to 531 mg/dl. Early atherosclerosis and endothelial cell proliferation in the thoracic aorta were quantified from en face specimens that were stained with hematoxylin and oil red O. Compared to the normotensive group, hypertensive 1K1C rats (1 and 2 weeks) had a 463% to 647% increase in the number of subendothelial macrophage‐foam cells/mm2. In 1K1C rats, foam cell accumulation was dense and widespread compared to a focal distribution of leukocytes in normotensive animals. Endothelial cell mitoses increased by 444% in hypertensive 1K1C rats at 1 week compared to the normotensive group. One or 2 weeks of captopril treatment of 1K1C rats reduced macrophage‐foam cells/mm2 by 62% to 72% compared to the hypertensive 1K1C group. Captopril decreased the rate of endothelial cell mitoses in 1K1C rats (1 week) by 62% compared to the hypertensive animals. The results indicate that macrophage‐foam cell accumulation was accelerated in the hypertensive 1K1C rats, and this was accompanied by an increased rate of endothelial cell turnover. Captopril lowered blood pressure, decreased the number of foam cells and inhibited the proliferation of arterial endothelial cells in 1K1C rats. © 1993 Wiley‐Liss, Inc.