The Renin-Angiotensin-Aldosterone System as a Therapeutic Target for Endothelial Dysfunction

Abstract

Endothelial dysfunction has been characterized by decreased nitric oxide (NO) synthesis or reduced NO bioavailability, which relates to inflammation, proliferation of smooth muscle cells, deposition of extracellular matrix, vasoconstriction, and a prothrombotic state within the vessel lumen. The endothelium is the site of the final step of synthesis of both NO and angiotensin II (Ang II) and is a major site for their countervailing interaction. Evidence suggests that renin-angiotensin system (RAS) blockade may have an impact on early mechanisms of vascular disease, such as endothelial dysfunction and vascular remodeling that underlie clinical manifestations of cardiovascular disease. This article reviews the current views on the biologic organization of RAS. Evidence supports a pathologic role of RAS activity in promoting endothelial dysfunction characterized by the impairment of NO bioavailability, and provides the basis for considering inhibition of RAS activity as a major target for therapeutic intervention.