THE ROLE OF ANGIOTENSIN II TYPE 2 RECEPTORS (AT2RS) IN THE REGULATION OF CARDIO-RENAL AND NEUROPROTECTIVE ACTIVITIES: POTENTIAL THERAPEUTIC IMPLICATIONS

Most of the physiological effects of the rennin-angiotensin system (RAS) are mediated by angiotensin II (AgII) type one receptors (AT1R), producing cellular dedifferentiation and proliferation; vasoconstriction; renal tubule sodium (Na+) reabsorption etc. However, the pathophysiologic role of AgII type two receptor (AT2R) has not been clearly defined yet. This review was, therefore, aimed at summarizing a plenty of primary literatures related to the role of AT2R. AT2R is a special G protein coupled receptor that is not coupled with the usual second messengers. The expression level of AT2R is greater in the neonates and fetal ages than in adults though its expression is up-regulated following tissue injury in adults implicating its role in regulating cell differentiation, growth and inflammations. Most of the cellular actions mediated by AT2R are counter regulatory to that of AT1R. AgII produces the cellular effects by acting on AT2R via different signal transduction pathways. The common cellular effects mediated by AT2R are antiproliferative, anti-inflammatory, vasodilation, natriuresis, etc which may be essential for modulating the cardiovascular, renal and brain injuries caused by different etiologies. The principal molecular signal transductions mediated by AT2R involve stimulation of the bradykinin and/or nitric oxide-cGMP pathwy, inactivation of mitogen activated protein kinase pathway by stimulating tyrosine and serine/threonien phosphatses, production of the neuroprotective factors, like BDNF, etc. These signaling pathways may exert cardio-renal and neuroprotective functions. Therefore, the development of drugs that stimulate the AT2R may the potential target to promote the treatment of different disorders related to the cardiovascular, renal and brain dysfunctions. Keywords: Angiotensin II, AT2R, cardiovascular system, Renal system, neuroprotection Â