Angiotensin II and coronary artery disease, congestive heart failure, and sudden cardiac death

An activated renin-angiotensin system is a major risk factor for cardiovascular events. Angiotensin II acts on AT1 and AT2 receptors. Stimulation of AT1 receptors is associated with endothelial dysfunction, mainly as the consequence of an increased vascular production of superoxide radicals, vasoconstriction, platelet activation, enhanced release of plasminogen activator inhibitor-1, activation of immediate early genes c-fos and c-jun, myocyte hypertrophy, connective tissue formation, endothelin-1 synthesis, and activation of growth factors like PDGF and TGF-beta 1. Stimulation of AT2 receptors can mitigate or abolish the growth promoting effects of AT1 receptor stimulation. The contribution of these effects--single or in combination--on the progression of atherosclerotic lesions, the phenomenon of restenosis and the process of remodeling in heart failure is being progressively elucidated. With increasing knowledge about these relationships the inhibition of AT1 receptors appears as a main target in preventive and reparative strategies in cardiovascular diseases.