Physiological and Pathophysiological Functions of the AT 2 Subtype Receptor of Angiotensin II

Abstract

Angiotensin II exerts a potent role in the control of hemodynamic and renal homeostasis. Angiotensin II is also a local and biologically active mediator involved in both endothelial and smooth muscle cell function acting on 2 receptor subtypes: type 1 (AT(1)R) and type 2 (AT(2)R). Whereas the key role of AT(2)R in the development of the embryo has been extensively studied, the role of AT(2)R in the adult remains more questionable, especially in humans. In vitro studies in cultured cells and in isolated segments of aorta have shown that AT(2)R stimulation could lead to the production of vasoactive substances, among which NO is certainly the most cited, suggesting that acute AT(2)R stimulation will produce vasodilation. However, in different organs or in small arteries isolated from different type of tissues, other vasoactive substances may also mediate AT(2)R-dependent dilation. Sometimes, such as in large renal arteries, AT(2)R stimulation may lead to vasoconstriction, although it is not always seen. In isolated arteries submitted to physiological conditions of pressure and flow, AT(2)R stimulation may also have a role in shear stress-induced dilation through a endothelial production of NO. Thus, when acutely stimulated, the most probable response expected from AT(2)R stimulation will be a vasodilation. Therefore, in the perspective of a chronic AT(1)R blockade in patients, overstimulation of AT(2)R might be beneficial, given their potential vasodilator effect. Concerning the possible role of AT(2)R in cardiovascular remodeling, the situation is more controversial. In vitro AT(2)R stimulation clearly inhibits cardiac and vascular smooth muscle growth and proliferation, stimulates apoptosis, and promotes extra cellular matrix synthesis. In vivo, the situation might be less beneficial if not deleterious; indeed, if chronic AT(2)R overstimulation would lead to cardiovascular hypertrophy and fibrosis, then the long-term consequences of chronic AT(1)R blockade, and thus AT(2)R overstimulation, require more in-depth analysis.