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

1 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.). 2 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. 3 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. 4 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. 5 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. 6 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.