Antagonizing the angiotensin II subtype 1 receptor: a focus on olmesartan medoxomil.
BACKGROUND
The orally active, nonpeptide antagonists of the angiotensin II subtype 1 (AT1) 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 AT1 receptor, with a main focus on the AT1 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 AT1 receptor antagonists and angiotensin-converting enzyme (ACE) inhibitors.


RESULTS
Olmesartan, the active metabolite of olmesartan medoxomil, is a highly potent antagonist of the AT1 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. AT1 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, AT1 receptor antagonists lack the nonangiotensin-related side effects such as cough and angioedema.


CONCLUSIONS
AT1 receptor antagonists such as olmesartan represent a valid therapeutic option for the treatment of hypertension and other cardiovascular and renal diseases.
Nussberger
Jürg
J
Division of Hypertension and Vascular Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. Juerg.Nussberger@chuv.hospvd.ch
Koike
Hiroyuki
H
D000799:Angioedema / Q000139:chemically induced; D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003371:Cough / Q000139:chemically induced; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D000068557:Olmesartan Medoxomil; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D013777:Tetrazoles / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D007093:Imidazoles; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D000068557:Olmesartan Medoxomil