The Renin-Angiotensin System as a Risk Factor and Therapeutic Target for Cardiovascular and Renal Disease

Abstract

ABSTRACT. The renin-angiotensin system (RAS) plays an important homeostatic role in BP regulation, water and salt balance, and tissue growth control under physiologic conditions. On the other hand, a pivotal involvement of the RAS in the pathophysiology of cardiovascular and renal disease is extensively supported by both basic and clinical evidence. In particular, it is today recognized that angiotensin II (AngII), the biologic effector of the RAS, may prompt a number of relevant structural and functional abnormalities through the activation of a complex of cellular effects mostly mediated via its binding with the AT1 subtype receptors. The key role of these AngII-linked mechanisms of disease is strongly corroborated by large interventional studies. In fact, pharmacologic interference with RAS activity, by both preventing AngII formation with angiotensin-converting enzyme inhibitors or antagonizing its binding to cell membrane receptors by selective antagonists, is associated with highly beneficial outcomes in major disease conditions (hypertension, diabetes, renal failure, heart failure, myocardial infarction, stroke, and others). This article briefly reviews the current views on the biologic organization of RAS evidence supporting a pathogenic role of the RAS activity in promoting cardiac, vascular, and renal disease, and finally provides the basis for considering inhibition of RAS activity a major target for therapeutic interventions in these conditions. E-mail: volpema@uniroma1.it