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.