Cytokine actions of angiotensin II.

Abstract

During the last few years, there has been an exponential rise in understanding functions and signal transduction mechanisms for angiotensin II (Ang II) type 2 receptors (AT2s).1 2 These studies are particularly relevant in view of the pivotal role of upregulation of AT2 in mediating tissue remodeling in many cardiovascular diseases, including vascular injury, atherosclerosis, cardiac hypertrophy, myocardial infarction, and congestive heart failure.1 Furthermore, Ang II type 1 receptor (AT1) antagonists, commonly used for treatment of hypertension and congestive heart failure, increase plasma levels of Ang II and upregulate AT2 expression. Under these conditions, the increase in AT2 is unopposed by AT1.1 3 Thus, understanding the role of AT2 in cardiovascular remodeling as well as the consequences of AT2 stimulation or inhibition during medical therapy is clinically important. AT2s only partially share the signaling mechanisms with AT1s and, in fact, counteract the signaling mechanisms activated by AT1s2 (Figure⇓). This negative nature of AT2 signaling has made the elucidation of its function more difficult than that of AT1. However, recent studies on the cardiovascular functions of AT2 seem to have reached a consensus: AT2s exert growth inhibitory effects either by suppressing cell proliferation and hypertrophy4 5 or by stimulating apoptosis.1 2 6 These actions alone may not explain the diverse cardiovascular phenomena attributed to AT2, resulting in unanswered questions. Why are AT2s abundant in growing fetal tissues? Why are AT2s abundant in tissues undergoing remodeling? Recently, an elegant genetic study has provided an answer to some of these questions, showing that an important function of AT2 in the fetal kidney is to stimulate apoptosis. Targeted …