Antagonizing the angiotensin II subtype I receptor: A focus on Olmesartan medoxornil

Background: The orally active, nonpeptide antagonists of the angiotensin II subtype 1 (AT(1)) receptor represent a recent class of antihypertensive drugs that selectively block the renin-angiotensin system. Olmesartan medoxomil is the newest member of this class. Objective: This article reviews the renin-angiotensin system and how this system can be pharmacologically inhibited by the selective antagonists of the AT(1) receptor, with a main focus on the AT(1) receptor antagonist olmesartan. Methods: Key studies were selected from previous work to illustrate the antihypertensive, cardioprotective, and renoprotective effects of olmesartan, and to compare class effects of AT(1) receptor antagonists and angiotensin-converting enzyme (ACE) inhibitors. Results: Olmesartan, the active metabolite of olmesartan medoxomil, is a highly potent antagonist of the AT(1) receptor. It inhibits the contractile responses to angiotensin II in guinea pig aorta, inhibits the pressor responses to angiotensin II in rats and dogs, and exhibits dose-dependent antihypertensive effects in spontaneously hypertensive rats. In addition to its antihypertensive effects, olmesartan medoxomil provides protection against cardiac and renal damage in animal models. AT(1) receptor antagonists are more specific inhibitors of the renin-angiotensin system compared with ACE inhibitors. They are well tolerated and have an excellent safety profile. Unlike angiotensin-converting enzyme inhibitors, AT(1) receptor antagonists lack the nonangiotensin-related side effects such as cough and angioedema. Conclusions: AT(1) receptor antagonists such as olmesartan represent a valid therapeutic option for the treatment of hypertension and other cardiovascular and renal diseases. Copyright (C) 2004 Excerpta Medica, Inc.