Aldosterone and Aldosterone Antagonism in Cardiovascular Disease

Aldosterone has long been known to mediate water and electrolyte balance by acting on mineralocorticoid receptors in the kidneys. However, recent studies have demonstrated the presence of these receptors in nonclassical locations, including the brain, blood vessels, and the heart. This finding suggests that aldosterone may play a larger role than once appreciated in normal physiologic function and cardiovascular disease. Some of the adverse cardiovascular effects that have been described include cardiac and vascular fibrosis, left ventricular hypertrophy, congestive heart failure, hypertension, endothelial dysfunction, reduced fibrinolysis, and cardiac arrhythmias. In light of these findings, aldosterone receptor blockers have become increasingly more important. This is especially true considering the fact that traditional therapies, such as angiotensin-converting enzyme inhibitors and angiotensin II-receptor blockers, may not be effective in maintaining long-term suppression of aldosterone. Therefore, a great deal of focus has been placed on spironolactone, which has proven to be an effective, albeit nonselective, aldosterone receptor blocker. The Randomized Aldactone Evaluation Study has shown that spironolactone results in a 30% reduction in mortality among patients with severe congestive heart failure. Other studies have shown spironolactone to lower high blood pressure, improve endothelial dysfunction, reduce left ventricular hypertrophy, and lower the incidence of fatal arrhythmias. However, spironolactone, because of its interaction with other steroid receptors, is not without its limitations, which include gynecomastia, breast tenderness, menstrual irregularities, and impotence. As a result, eplerenone (INSPRA), a selective aldosterone blocker, is currently being investigated for its efficacy and side-effect profile compared with spironolactone. Eplerenone has already been approved for the treatment of systemic hypertension, and several clinical trials are currently underway to identify other therapeutic uses for this agent in cardiovascular disease management.