Role of mineralocorticoid receptor antagonists in cardiovascular disease.

Aldosterone exerts its best known sodium homeostasis actions by controlling sodium excretion at the level of the distal tubules via activation of the apical epithelial sodium channel and the basolateral Na(+)/K(+)ATPase pump. Recently, this mineralocorticoid hormone has been demonstrated to act on the heart and blood vessels. Excess release of aldosterone in relation to the salt status induces both genomic and nongenomic effects that by promoting endothelial dysfunction, and vascular and cardiorenal adverse remodeling, contribute to the target organ damage found in hypertension, heart failure, myocardial infarction, and chronic renal failure. Mineralocorticoid receptor blockers have been shown to be highly effective in resistant hypertension and to slow down heart failure progression, and in experimental animals, the development of atherosclerosis. Blockade of the action of aldosterone and potentially other mineralocorticoid steroids has been increasingly demonstrated to be an extremely beneficial therapy in different forms of cardiovascular disease. This review provides a summary of the knowledge that exists on aldosterone actions in the cardiovascular system and, in providing the translational impact of this knowledge to the clinical arena, illustrates how much more needs to be achieved in exploring the use of mineralocorticoid receptor blockers in less advanced stages of heart, renal, and vascular disease.