Angiotensin II: a vasoactive hormone with ever-increasing biological roles.

Abstract

Angiotensin II (Ang II) is an octapeptide hormone that plays a central role in cardiovascular homeostasis. Typical of many proteins, Ang II was named on the basis of its first-demonstrated biological function—the ability to act as a vasoactive agonist and induce contraction of blood vessels. Over the years, Ang II has been shown to play important roles in mediating hypertension, heart failure, cardiac remodeling, diabetes, and the proliferative and inflammatory responses to arterial injury (see review1). These findings have spawned the development of several classes of pharmacological agents designed at inhibiting the synthesis of Ang II (eg, angiotensin II-converting enzyme inhibitors) or blocking its action (eg, angiotensin II receptor antagonists). These agents are now widely used in the treatment of hypertension and congestive heart failure. In conjunction with studies performed on animal models, there have been numerous studies examining the cellular effects of Ang II. Initial studies focused in particular on the role of Ang II as a contractile agonist and therefore on the signals induced by Ang II in vascular smooth muscle cells (SMCs) and cardiomyocytes associated with contraction, such as the mobilization of intracellular calcium ([Ca2+]i) and the activation of protein kinase C (PKC). It was demonstrated that Ang II activated phospholipase C, resulting in the production of inositol trisphosphate (IP3) and diacylglycerol, which in turn were responsible for the mobilization of [Ca2+]i and the activation of PKC, respectively. Additional studies in SMC cultures examined the properties of Ang II as a growth agonist, in particular its role in promoting cellular hypertrophy, characterized by increases in protein synthesis, cell size, and polyploidy.2,3 The cloning and expression of the Ang II receptor,4,5 together with substantial progress in signal transduction, have greatly expanded our knowledge of Ang II-mediated cellular events …