Abstract
The role of aldosterone has expanded from the hormone's genomic effects that involve renal sodium transport to nongenomic effects that are independent of the effect of aldosterone on sodium transport. The nongenomic effects of aldosterone to increase fibrosis, collagen deposition, inflammation, and remodeling of the heart and blood vessels, however, are markedly increased in the presence of high sodium intake. The genomic effect of aldosterone increases renal sodium transport, but the administration of large doses of aldosterone to normal individuals does not cause edema, relating to the phenomenon of "aldosterone escape"; however, in edematous disorders including cardiac failure, cirrhosis, and nephrotic syndrome, impaired aldosterone escape leads to renal sodium retention and edema formation. There is now considerable evidence for the nongenomic effects of aldosterone in several important diseases. Thus, low dosages of mineralocorticoid antagonists, with little or no effect on urinary sodium excretion, have been shown to afford a beneficial effect on morbidity and mortality in patients with advanced cardiac failure and after acute myocardial infarction. Three-drug-resistant hypertension has also been found to respond to spironolactone in modest dosages. The combination of an angiotensin converting enzyme inhibitor (ACEI) with spironolactone to treat such resistant hypertension may be more effective than adding an angiotensin receptor blocker to an ACEI. The role of spironolactone has also been shown to decrease albuminuria in chronic kidney disease including diabetic nephropathy in the presence of maximal dosages of ACEI. The effect of aldosterone in metabolic syndrome is also discussed in this review.