Angiotensin II receptor blockade and ventricular remodelling

Abstract

Cardiac remodelling is the expression of molecular, cellular and interstitial changes in response to cardiac injury, manifesting as adverse alterations in the size, shape and function of the ventricle. Several clinical studies have documented significant elevations in the levels of renin, angiotensin II (Ang II) and aldosterone attending acute myocardial infarction and/or congestive heart failure. Similar to catecholamines, markedly elevated activity of the renin-angiotensin-aldosterone system (RAAS) is associated with poor prognosis. The effects of Ang II upon cardiac tissue are related to two primary receptors, Ang II type 1 (AT1) and Ang II type 2 (AT2). The AT1-receptor appears to mediate many of the deleterious effects of chronic RAAS activity, while the AT2-receptor is increasingly shown to have potential cardioprotective effects. Attenuating the deleterious effects of sustained Ang II stimulation can be achieved by direct inhibition of angiotensin-converting enzyme (ACE) and/or direct antagonism of AT receptors. ACE inhibition reduces left ventricular (LV) volumes, retards the progression of LV dilatation and hypertrophy and increases systolic function in systolic dysfunction. By blocking at the receptor level, Ang II receptor blockers (ARBs) provide an alternative and more direct approach to inhibiting the effects of Ang II; however, data relating to their effects upon ventricular remodelling, whether used in isolation or in combination with ACE inhibitors (ACE-Is), are less convincing. Data arising from several recent clinical trials suggest that simultaneous use of ACE-Is and ARBs maybe of more benefit in attenuating ventricular remodelling than either agent alone.