Physiological and pathophysiological functions of the AT(2) subtype receptor of angiotensin II - From large arteries to the microcirculation

Angiotensin II exerts a potent role in the control of hemodynamic and renal homeostasis. Angiotensin II is also a local and biologically active mediat or 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 ro le 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 h umans. 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 vasoact ive 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 vasoconst riction, 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 producti on of NO. Thus. when acutely stimulated, the most probable response expecte d from AT(2)R stimulation will be a vasodilation. Therefore, in the perspec tive of a chronic AT(2)R blockade in patients, overstimulation of AT(2)R mi ght be beneficial, given their potential vasodilator effect. Concerning the possible role of AT(2)R in cardiovascular remodeling, the si tuation is more controversial. In vitro AT(2)R stimulation clearly inhibits cardiac and vascular smooth muscle growth and proliferation, stimulates ap optosis, and promotes extra cellular matrix synthesis. In vivo, the situati on might be less beneficial if not deleterious; indeed, if chronic AT(2)R o verstimulation would lead to cardiovascular hypertrophy and fibrosis, then the long-term consequences of chronic AT(1)R blockade. and thus AT(2)R over stimulation, require more in-depth analysis.