On the biological actions of intracellular angiotensin.

Abstract

Over the last 2 decades, it has become clear that angiotensin can be generated not only in the systemic circulation but also in multiple tissue sites, where its production can be regulated by local factors. Given the ability of angiotensin II to influence target cell proliferation, hypertrophy, and apoptosis, tissue angiotensin systems potentially play an important role in a wide variety of physiological processes. In this issue of Hypertension , De Mello and Danser1 review the evidence for the synthesis of angiotensin II in the heart and discuss its possible role in health and disease. Their review complements other recent reviews of this subject, such as that by Dostal and Baker.2 Uniquely, however, the present review discusses the potential role of intracellular angiotensin II, called intracrine angiotensin II, in intercellular signaling and calcium flux in the heart. These findings are based on De Mello’s studies1 of renin, angiotensin I, and angiotensin II dialyzed into rat cardiac cells. The evidence for the influence of an intracellular AT1-like angiotensin II receptor on intercellular communication is compelling and supports the concept of an intracrine angiotensin II system in the heart, with possible implications for cardiac conduction and contractility in health and disease. Also, the review emphasizes the potential importance of the uptake of prorenin by cells and its subsequent activation …