Novel actions of angiotensin II via its renal type-2 (AT2) receptor |
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Authors: | Robert M. Carey MD Zhi-Qin Wang MD Helmy M. Siragy MD |
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Affiliation: | (1) Department of Medicine, University of Virginia Health Sciences Center, Box 395, 22908 Charlottesville, VA, USA |
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Abstract: | The vast majority of the biologic effects of angiotensin II have been considered to be mediated by the subtype-1 (AT1) receptor. The AT2 receptor is expressed to a low degree in most adult cells and tissues, and its function has not been understood. Recent studies, however, have identified novel actions of angiotensin II mediated by the AT2 receptor in the kidney. These AT2 receptor actions have importance in the control of blood pressure and hypertension. The AT2 receptor mediates a renal vasodilator cascade, including generation of bradykinin, nitric oxide, and cyclic GMP. This action of angiotensin II occurs when the renin-angiotensin system is activated, as in sodium depletion. The AT2 receptor also appears to mediate prostaglandin (PG) Fα formation, probably by stimulating conversion of PGE2 to PGFα. The AT2 receptor plays a counter-regulatory vasodilator role opposing the vasoconstrictor actions of angiotensin II. The AT1 and AT2 receptors engage in inter-receptor “cross-talk.” In the absence of the AT2 receptor, sustained angiotensin II pressor and antinatriuretic hypersensitivity occurs, mediated by a deficiency of bradykinin, nitric oxide, and cyclic GMP. The AT2 receptor may play an important role in stimulating pressure natriuresis, but definitive studies are required to resolve this issue. The AT2 receptor mediates several renal actions of angiotensin II, appears to be important in the physiologic regulation of blood pressure, and may be involved in the pathophysiology of hypertension. |
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