Antagonizing the Angiotensin II Subtype I Receptor: A Focus on Olmesartan Medoxomil

Abstract Background: The orally active, nonpeptide antagonists of the angiotensin II subtype 1 (AT,) 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.