Use of angiotensin II receptor blockers in animal models of atherosclerosis.

Long considered independent risk factors for end-stage vascular disease, hypertension and atherosclerosis may be intimately linked through their effects on vascular endothelial dysfunction, which are mediated by the renin-angiotensin system (RAS). Angiotensin II, a potent vasoconstrictor and the principal active peptide of the RAS, can also produce structural changes in the vessel wall associated with atherosclerosis. The role of RAS in the pathogenesis of atherosclerosis is supported by several lines of evidence, including the presence and upregulation of angiotensin-converting enzyme (ACE) and angiotensin II in the walls of atherosclerotic arteries. This article reviews recent research showing that administration of the angiotensin II type 1-receptor blocking agents (ARB) losartan and olmesartan medoxomil to cynomolgus monkeys with diet-induced hyperlipidemia prevents the progression of atherosclerosis. Since these effects have been achieved without altering blood pressure or plasma cholesterol levels significantly, it is suggested that these novel effects of angiotensin II receptor blocker treatment may extend the therapeutic profile of this class of agents in the prevention of human vascular disease.