Anti‐atherosclerotic effects of an angiotensin converting enzyme inhibitor and an angiotensin II antagonist in Cynomolgus monkeys fed a high‐cholesterol diet

Abstract

We investigated the relationship between angiotensin II formation and the development of atherosclerotic lesions in the aorta of monkeys (Macaca fascicularis) fed a high‐cholesterol (4% cholesterol and 6% corn oil) diet for 6 months, and studied the effects of an angiotensin converting enzyme (ACE) inhibitor, trandolapril (10 mg kg⁻¹ per day, p.o.), and an angiotensin II type 1 receptor antagonist, 2‐butyl‐4‐(methylthio)‐1‐[[2′[[[(propylamino)carbonyl]amino]sulfonyl](1,1′‐biphenyl)‐4‐yl]methyl]‐1H‐imidazole‐5‐carboxylate (HR 720; 20 mg kg⁻¹ per day, p.o.). The level of low‐density lipoprotein was significantly increased by the cholesterol diet, whereas that of high‐density lipoprotein was significantly decreased. The relative areas of the atherosclerotic lesions in the thoracic aorta in the normal and cholesterol‐diet groups were 1.3±0.3 and 64±10%, respectively. Plasma renin and ACE activities showed no differences between the normal and cholesterol‐diet groups. ACE activity and the concentration of angiotensin II were significantly increased in the aorta of the cholesterol‐fed monkeys. Trandolapril and HR 720 decreased significantly the area of the atherosclerotic lesions in the thoracic aorta of cholesterol‐fed monkeys, but not the mean blood pressure and the levels of low‐density and high‐density lipoproteins. In plasma and aorta, trandolapril, but not HR 720, decreased significantly the ACE activities in the cholesterol‐fed monkeys, while both of these drugs decreased significantly the angiotensin II levels. In conclusion, blockade of angiotensin II function in vascular tissues by trandolapril or HR 720 may play an important role in preventing the development of atherosclerotic lesions. British Journal of Pharmacology (1999) 128, 523–529; doi:10.1038/sj.bjp.0702833