Angiotensin II receptor blockers: review of the binding characteristics

Several angiotensin II receptor blockers (ARBs), including candesartan cilexetil, irbesartan, losartan, telmisartan, and valsartan, are currently approved by the US Food and Drug Administration (FDA) for the treatment of patients with hypertension. These agents share a common mechanism of action—antagonism of the angiotensin type 1 (AT1) receptor—and as a result, they block a number of angiotensin II effects that are relevant to the pathophysiology of cardiovascular disease, including vasoconstriction, renal sodium reabsorption, aldosterone and vasopressin secretion, sympathetic activation, and vascular and cardiac hyperplasia and hypertrophy. Unlike the angiotensin converting enzyme (ACE) inhibitors, these new drugs block the effects of angiotensin II regardless of whether it is produced systemically in the circulation or locally via ACE- or non–ACE-dependent pathways in tissues. ARBs also block the angiotensin II–induced feedback regulation of renin release, resulting in an increase in angiotensin II levels. With the AT1 receptor blocked, angiotensin II is available to activate the angiotensin type 2 (AT2) receptor, which mediates several potentially beneficial effects in the cardiovascular system, including vasodilation, antiproliferation, and apoptosis. Thus, ARBs provide a highly selective approach for regulating the effects of angiotensin II.