Aldosterone receptor antagonists: current perspectives and therapies

Jason L Guichard, Donald Clark III, David A Calhoun, Mustafa I Ahmed

University of Alabama at Birmingham, Department of Medicine, Division of Cardiovascular Disease, Vascular Biology and Hypertension Program, Birmingham, AL, USA

Abstract: Aldosterone is a downstream effector of angiotensin II in the renin–angiotensin–aldosterone system and binds to the mineralocorticoid receptor. The classical view of aldosterone primarily acting at the level of the kidneys to regulate plasma potassium and intravascular volume status is being supplemented by evidence of new “off-target” effects of aldosterone in other organ systems. The genomic effects of aldosterone are well known, but there is also evidence for non-genomic effects and these recently identified effects of aldosterone have required a revision in the traditional view of aldosterone's role in human health and disease. The aim of this article is to review the biological action of aldosterone and the mineralocorticoid receptor leading to subsequent physiologic and pathophysiologic effects involving the vasculature, central nervous system, heart, and kidneys. Furthermore, we outline current evidence evaluating the use of mineralocorticoid receptor antagonists in the treatment of primary aldosteronism, primary hypertension, resistant hypertension, obstructive sleep apnea, heart failure, and chronic kidney disease.

Keywords: aldosterone antagonist, mineralocorticoid receptor antagonist, primary aldosteronism, hypertension, obstructive sleep apnea, heart failure, chronic kidney disease