(Hypertension. 2000;35:155.)
© 2000 American Heart Association, Inc.
State-of-the-Art Lectures |
Role of the Angiotensin Type 2 Receptor in the Regulation of Blood Pressure and Renal Function
From the Department of Medicine, University of Virginia School of Medicine, Charlottesville, Va.
Correspondence to Robert M. Carey, MD, Box 395, University of Virginia Health System, Charlottesville, VA 22908. E-mail RMC4c{at}virginia.edu
Abstract—The renin-angiotensin system is a major physiological regulator of body fluid volume, electrolyte balance, and arterial pressure. Virtually all of the biological actions of the principle effector peptide angiotensin II (ANG II) have been attributed to an action at the type 1 (AT1) ANG receptor. Until recently, the functional role of the type 2 (AT2) receptor, if any, has been unknown, possibly because the AT2 receptor has a low degree of expression compared with that of the AT1 receptor. Evidence has now accumulated that the AT2 receptor opposes functions mediated by the AT1 receptor. Whereas the AT1 receptor stimulates cell proliferation, the AT2 receptor inhibits proliferation and promotes cell differentiation. These differences in growth responses have been ascribed to different cell signaling pathways in which the AT1 receptor stimulates protein phosphorylation and the AT2 receptor dephosphorylation. During the past 5 years, studies have demonstrated that the AT2 receptor is responsible for vasodilation and natriuresis, thus opposing the vasoconstrictor and antinatriuretic effects of ANG II mediated through the AT1 receptor. Work from our laboratory and others indicates that the AT2 receptor stimulates vasodilation and natriuresis by an autocrine cascade including bradykinin, nitric oxide, and cyclic GMP. The AT2 receptor also has been found to control vasodilator prostaglandins, which have a role in blood pressure regulation. The AT2 receptor appears to play a counterregulatory protective role in the regulation of blood pressure and sodium excretion that opposes the AT1 receptor.
Key Words: angiotensin II • receptors, angiotensin II • blood pressure • kidney • sodium
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