The Nongenomic Actions of Aldosterone

Aldosterone has physiological effects to regulate fluid and electrolyte homeostasis across epithelia and proinflammatory effects on a variety of nonepithelial cells in the context of inappropriate salt status. These effects are mediated by mineralocorticoid receptors, members of a large family of nuclear transcription factors, by DNA-directed, RNA-mediated protein synthesis. Rapid effects of aldosterone, insensitive to actinomycin D or cycloheximide and thus clearly nongenomic, have been convincingly documented in a variety of epithelial and nonepithelial tissues. Despite strenuous attempts, isolation of a nonclassical membrane receptor for aldosterone has proven unsuccessful, and rapid nongenomic effects mediated by classical mineralocorticoid receptors are increasingly recognized in the kidney, heart, and vascular wall. The mechanism of rapid nongenomic actions of aldosterone may vary between tissues in terms of pathways; in addition, what remains to be established is the physiological role of aldosterone action via such rapid nongenomic mechanisms and how they might synergize with the longer time course genomic actions of mineralocorticoids.