Mechanism of action of angiotensin-receptor blocking agents.

Angiotensin II is the most active hormone of the renin-angiotensin system. In humans, two angiotensin receptors have been identified: AT(1) and AT(2). In adults, most of the effects of angiotensin II are mediated by the AT(1) receptor; the function of the AT(2) receptor is not yet well established. Angiotensin II has both systemic and local paracrine effects. Increased activity of angiotensin II and stimulation of the AT(1) receptor have been linked to the development of several cardiovascular and renal diseases, including hypertension, heart failure, left ventricular hypertrophy, and diabetic nephropathy. Over the past two decades, angiotensin-converting enzymes have been used to manage these diseases. However, the side effects and less-than- maximum therapeutic effects of angiotensin-converting enzyme inhibitors, particularly in the decrease of mortality associated with congestive heart failure, have led to the development of AT(1)-receptor blockers.