Progression of Cardiovascular Damage: The Role of Renin–Angiotensin System Blockade

Abstract

The renin-angiotensin system (RAS) plays key roles throughout the cardiovascular continuum, and blockade of this system--either through angiotensin-converting enzyme (ACE) inhibition or through angiotensin II type 1 (AT(1)) receptor antagonism--now occupies a central place in the management of cardiovascular disease (CVD). Understanding of the RAS has expanded in recent years with the identification of new pathways for formation of angiotensin II and novel effector peptides, such as angiotensin-(1-7), which may constitute new therapeutic targets. A substantial proportion of the benefits of ACE inhibitors, including vasodilation, improvements in endothelial function, and inhibition of cell proliferation, appear to be attributable to decreases in angiotensin II and increases in bradykinin. In addition, however, there is evidence that other mechanisms, such as modulation of ACE signaling, may also contribute. Angiotensin receptor blockers (ARBs) selectively block AT(1) receptors and allow unopposed stimulation of AT(2) receptors, with potentially beneficial vasodilatory, anti-inflammatory, and antiproliferative effects. As a result, these agents share many of the clinical benefits of ACE inhibitors. Both ACE inhibitors and ARBs have been shown to exert multiple antiatherogenic actions, and to reduce clinical events in high-risk participants; their use is recommended in current guidelines for the secondary prevention of CVD.