Angiotensin II receptor blockade and end-organ protection

The renin-angiotensin system (RAS) is a widely studied hormonal system that comprises substrate-enzyme interactions, the end result of which is production of the active peptide angiotensin II (Ang II). Because Ang II affects blood pressure control, sodium and water homeostasis, and cardiovascular function and structure, a great deal of research effort has been directed toward blocking the RAS. Angiotensin II may also be involved in end-organ damage in hypertension, heart failure, and vascular disease. At least two subtypes of angiotensin II receptors have been identified: AT(1) and AT(2). The AT(1) mediates all of the known actions of Ang II on blood pressure control. Additionally, research has indicated that the AT(1) receptor modulates cardiac contractility and glomerular filtration, and increases renal tubular sodium reabsorption, and cardiac and vascular hypertrophy. Less is known regarding the function of the AT(2) receptor. Evidence suggests that the AT(2) receptor inhibits cell proliferation and reverses AT(1)-induced hypertrophy. Indeed, these receptors are thought to exert opposing effects. Angiotensin II AT(1) receptor antagonists (AT(1)RA) inhibit the RAS at the receptor level by specifically blocking the AT(1) receptor subtype. These drugs induce a dose-dependent blockade of Ang II effects, resulting in reduced blood pressure, urinary protein, and glomerular sclerosis. It is postulated that AT(1)RA may provide end-organ protection by blocking Ang II effects via the AT(1) receptor, yet leaving the AT(2) receptor unopposed. Consequently, these agents may reduce the morbidity and mortality that result from myocardial infarction (MI) and other conditions resulting from structural alterations in the heart, kidney, and vasculature. Am J Hypertens 1999; 12:150S-156S (C) 1999 American Journal of Hypertension, Ltd.