Aldosterone exerts a multiple physiologic actions that raise blood pressure, including mediation of increased extracellular fluid volume and promotion of vasoconstriction. Other pathophysiologic actions of aldosterone that promote hypertension, end-organ damage and increased cardiovascular risk involve endothelial dysfunction, activation of plasminogen activator inhibitor-1, increased potential for cardiac arrhythmias, fibrosis in the heart, kidneys and vasculature. The endocrine or paracrine properties of aldosterone are transduced via nuclear receptors in the epithelial cells of various organs.
Because aldosterone appears to be a relevant risk factor for cardiovascular disease, the use of aldosterone blockers could provide benefit in the treatment of hypertensive endorgan damage.
In animal models aldosterone blockade attenuates cardiac fibrosis, aortic fibrosis, improves large arterial compliance and protects endothelial function. Hemodynamic and humoral actions of aldosterone have important clinical implications for the use of aldosterone blockers in hypertension and cardiovascular and renal diseases.
Clinical trials have shown that spironolactone reduces cardiac and vascular collagen turnover, reduces ventricular arrhythmias and dilates blood vessels. Aldosterone blockers are effective in the therapy of hyperaldosteronism.
In a clinical study of congestive heart failure - RALES - spironolactone when given in addition to conventional therapy reduced mortality and heart failure hospitalizations as compared to placebo. In recent studies new selective aldosterone blocker - eplerenone - effectively lowered blood pressure in patients with essential hypertension, reduced left ventricular hypertrophy and exerted beneficial effect in patients with post-myocardial left ventricular dysfunction.