doi: 10.1161/hy1101.096109
(Hypertension. 2001;38:1150.)
© 2001 American Heart Association, Inc.
Fourth Workshop on Structure and Function |
Physiological and Pathophysiological Functions of the AT2 Subtype Receptor of Angiotensin II
From Large Arteries to the Microcirculation
From Institut National de la Santé et de la Recherche Médicale (INSERM) U 541, IFR Circulation-Paris VII, Université Paris VII (D.H., B.I.L.); and Department of Physiology, AP-HP-Hôpital Lariboisière (N.K., B.I.L.), Paris, France.
Correspondence to Bernard I. Levy, INSERM U541, 41 Bd de la Chapelle, 75475 Paris, France. E-mail levy{at}infobiogen.fr
Abstract
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 (AT1R) and type 2 (AT2R). Whereas the key role of AT2R in the development of the embryo has been extensively studied, the role of AT2R in the adult remains more questionable, especially in humans. In vitro studies in cultured cells and in isolated segments of aorta have shown that AT2R stimulation could lead to the production of vasoactive substances, among which NO is certainly the most cited, suggesting that acute AT2R stimulation will produce vasodilation. However, in different organs or in small arteries isolated from different type of tissues, other vasoactive substances may also mediate AT2R-dependent dilation. Sometimes, such as in large renal arteries, AT2R stimulation may lead to vasoconstriction, although it is not always seen. In isolated arteries submitted to physiological conditions of pressure and flow, AT2R 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 AT2R stimulation will be a vasodilation. Therefore, in the perspective of a chronic AT1R blockade in patients, overstimulation of AT2R might be beneficial, given their potential vasodilator effect.
Concerning the possible role of AT2R in cardiovascular remodeling, the situation is more controversial. In vitro AT2R 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 AT2R overstimulation would lead to cardiovascular hypertrophy and fibrosis, then the long-term consequences of chronic AT1R blockade, and thus AT2R overstimulation, require more in-depth analysis.
Key Words: blood pressure • growth • hypertrophy • vascular • endothelium • relaxation
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