Role for aldosterone in cardiovascular injury

Recent work has demonstrated that aldosterone has important extra-renal effects by which it can contribute to cardiovascular disease. This review discusses studies that have increased the understanding of the harmful effects of aldosterone on the cardiovascular system and have demonstrated broad benefits of mineralocorticoid receptor blockade in managing cardiovascular disease. By demonstrating protection with MR antagonism, animal and human studies show that MR activation contributes to cardiac damage, cerebrovascular disease, and nephropathy. Protection by MR antagonists can occur in the absence of blood pressure reductions and can occur in settings of low or normal plasma aldosterone levels or with concurrent ACE inhibition. Recently shown effects of aldosterone on myocytes, fibroblasts, and vascular endothelial cells may contribute to MR-mediated cardiovascular damage. An early event in aldosterone-mediated injury appears to be the development of vascular inflammation and dysfunction. Thus, an MR-mediated vasculopathy likely represents an important mechanism underlying the widespread adverse effects of aldosterone on the cardiovascular system. There is new compelling basic and clinical data to suggest that aldosterone has extra-renal actions, including pro-inflammatory effects, which make it an important contributor to cardiovascular injury. We anticipate that future clinical trials will expand the indications for aldosterone blockade in the management of cardiovascular disease.