Mechanisms of angiotensin II type 1 receptor blocker for anti-atherosclerotic effect in monkeys fed a high-cholesterol diet.

Abstract

OBJECTIVE To clarify the mechanism of the anti-atherosclerotic effect of angiotensin II type 1 receptor blocker (ARB) in primates, we investigated whether an ARB (CS-866) affects the serum markers of inflammation and growth factors, and the endothelial function in monkeys fed a high-cholesterol diet. DESIGN Monkeys fed a high-cholesterol diet for 6 months were divided into two groups: one group was given an ARB, CS-866 (10 mg/kg per day), and the other group was not. The control group was fed a normal diet. RESULTS Blood pressure and the plasma cholesterol level were not affected by CS-866. Plasma levels of angiotensin II, renin, angiotensin converting enzyme and chymase were not changed by the high-cholesterol diet, whereas vascular angiotensin converting enzyme, but not chymase, was significantly increased. Serum levels of macrophage-colony stimulating factor, transforming growth factor-beta1 and intracellular adhesion molecule-1 were significantly increased in monkeys fed a high-cholesterol diet but they were suppressed by CS-866. The relaxation response of isolated carotid arteries to acetylcholine was suppressed in the high-cholesterol group, whereas it was improved by CS-866. CONCLUSIONS CS-866 reduced lipid deposition along with the suppression of serum macrophage-colony stimulating factor, transforming growth factor-beta 1 and intracellular adhesion molecule-1, and the improvement of vascular functions, suggesting that ARB has multiple mechanisms for reducing lipid deposition in primates.