Aldosterone Receptor Antagonists for Hypertension

Abstract

Aldosterone is an important and independent target for therapeutic intervention in hypertension and hypertension-related diseases. Its actions, once thought to be limited to the distal convoluted tubule of the kidney, are now recognised to be wide-ranging, including interactions with mineralocorticoid receptors in diverse cardiovascular sites to mediate vascular and myocardial remodelling and dysfunction. The latter are referred as non-epithelial actions.

Spironolactone, an aldosterone receptor antagonist, is indicated for the treatment of mineralocorticoid hypertension, but its use is limited by an adverse effect profile that includes not only by hyperkalaemia, but also antiandrogenic and progestational effects resulting from its poor specificity for the aldosterone receptor. Eplerenone is the first selective aldosterone receptor antagonist to be developed and recently gained approval from the US FDA for treatment of systemic hypertension. This was based on studies which demonstrated that eplerenone had a blood pressure-lowering profile that was equivalent to existing antihypertensive agents, was useful for treatment of low-renin and systolic hypertension, maintained utility even as add-on therapy to other antihypertensive agents, and exerted beneficial effects on hypertension-related left ventricular hypertrophy and renal impairment. Perhaps most notably, eplerenone was generally well tolerated, and did not cause the antiandrogenic and progestational adverse effects commonly observed with spironolactone.