CAPTOPRIL DECREASES ACCELERATED ATHEROSCLEROSIS IN HYPERTENSIVE ONE-KIDNEY ONE-CLIP RATS FED CHOLESTEROL

The effect of captopril treatment on early atherosclerosis was determi ned in cholesterol-fed rats with acute renovascular hypertension. Thre e groups were established: normotensive rats, hypertensive one kidney one clip (1K1C) rats, and 1K1C rats treated with 27 mg/kg/day of capto pril. Animals in the 3 groups received chow containing 4% cholesterol and 1% cholic acid. Cholesterol feeding and drug treatment were starte d immediately following surgery, then after 1 or 2 weeks, mean arteria l pressure, heart rate, and plasma lipids were measured; and the thora cic aorta was perfused with formalin. One or 2 weeks after surgery, me an arterial pressure increased by 17% to 22% in the 1K1C group compare d to the normotensive animals. Captopril decreased blood pressure in t he 1K1C rats by 22% to 25% compared to the hypertensive 1K1C group. In the 3 sets of rats, plasma cholesterol was similarly elevated from 10 9 to 531 mg/dl. Early atherosclerosis and endothelial cell proliferati on in the thoracic aorta were quantified from en face specimens that w ere stained with hematoxylin and oil red O. Compared to the normotensi ve group, hypertensive 1K1C rats (1 and 2 weeks) had a 463% to 647% in crease in the number of subendothelial macrophage-foam cells/mm2. In 1 K1C rats, foam cell accumulation was dense and widespread compared to a focal distribution of leukocytes in normotensive animals. Endothelia l cell mitoses increased by 444% in hypertensive 1K1C rats at 1 week c ompared to the normotensive group. One or 2 weeks of captopril treatme nt of 1K1C rats reduced macrophage-foam cells/mm2 by 62% to 72% compar ed to the hypertensive 1K1C group. Captopril decreased the rate of end othelial cell mitoses in 1K1C rats (1 week) by 62% compared to the hyp ertensive animals. The results indicate that macrophage-foam cell accu mulation was accelerated in the hypertensive 1K1C rats, and this was a ccompanied by an increased rate of endothelial cell turnover. Captopri l lowered blood pressure, decreased the number of foam cells and inhib ited the proliferation of arterial endothelial cells in 1K1C rats.