Aldosterone

ALDOSTERONE

Aldosterone, produced by the adrenal cortex, acts at ep-ithelial cells in the distal tubule of the nephron to in-crease the reabsorption of sodium and is therefore con- sidered an important hormone in the regulation of elec-trolyte balance. Aldosterone exerts its effects at the nephron through mineralocorticoid receptors, which translocate to the nucleus upon aldosterone binding and exert genomic effects leading to increased sodium reabsorption. In addition to the epithelial effects of al-dosterone at mineralocorticoid receptors, nonepithelial cells, including cardiac muscle and vascular smooth muscle cells and cells in the brain, can respond to al-dosterone and result in left ventricular hypertrophy, cardiac and vascular fibrosis, and stimulation of sympa-thetic nervous system activity.

Spironolactone (Aldactone), an antagonist of the al-dosterone mineralocorticoid receptor, is used to treat pri-mary aldosteronism, essential hypertension, and conges-tive heart failure . In the treatment of hypertension resulting from adrenal adenoma (primary al-dosteronism) and in patients with essential hypertension, spironolactone lowers blood pressure primarily through blockade of epithelial mineralocorticoid receptors in the kidney, reductions in sodium and water reabsorption, and diuresis. The use of spironolactone in the treatment of es-sential hypertension is typically restricted to patients who do not respond appropriately to other agents and is often used in combination drug therapy. In large-scale clinical trials in patients with severe heart failure, administration of spironolactone markedly reduced morbidity and mor-tality without reducing blood pressure. Spironolactone is used to treat patients with moderate to severe heart failure who exhibit symptoms and ventricular dysfunction despite treatment with an ACE inhibitor or a diuretic.

Adverse effects of spironolactone therapy include hyperkalemia, gastrointestinal problems, gynecomastia (breast enlargement in males), and impotence. Gyneco-mastia and impotence arising from spironolactone treatment are results of significant blockade of the an-drogen and mineralocorticoid receptors. Novel selective mineralocorticoid receptor antagonists, such as eplere-none, are in clinical trials.