Aldosterone antagonists in the treatment of hypertension and target organ damage

Mineralocorticoids mediate a number of effects besides regulation of fluid and electrolyte balance. Recent evidence has revealed several nontraditional roles, sites of synthesis, and action for these steroids. Aldosterone, the principal mineralocorticoid in humans, appears to be synthesized in physiologically relevant amounts in both the heart and the vasculature, and plays an important role in vessel wall and myocardial remodeling. The genomic effects of aldosterone are mediated through activation of the classic mineralocorticoid receptor, whereas rapid nongenomic effects seem to involve a distinct receptor and result in activation of multiple downstream signaling pathways. Recently, several lines of evidence seem to suggest an important interaction between the nitric oxide and the aldosterone pathway in the adrenal gland and vasculature. The evolution of selective aldosterone receptor antagonists will help us understand the role that mineralocorticoids play in the pathogenesis of hypertension, heart failure, and atherosclerosis.