Mineralocorticoid receptors and pathophysiological roles for aldosterone in the cardiovascular system.
For almost 40 years since its discovery in 1953, the mineralocorticoid hormone, aldosterone, was considered to affect blood volume, and thus blood pressure, by its action to retain sodium at epithelial tissues. Over the past decade, direct effects of aldosterone on the heart and blood vessels, and on the cerebral control of blood pressure, have been established in experimental animals. Simultaneously, the incidence of primary aldosteronism in essential hypertension is now acknowledged to be 10-20%, rather than <or= 1%, underscoring a previously unrecognized role for aldosterone in hypertension. The 30% improvement in mortality (and 35% in morbidity) seen in the RALES trial with the addition of low-dose spironolactone to best practice therapy in moderate to severe heart failure, similarly points to an unrecognized role for aldosterone in the pathophysiology of heart failure. Currently, both experimental and clinical studies are directed towards establishing the mechanisms involved in these pathophysiological effects of aldosterone in the cardiovascular system, and of the role of mineralocorticoid receptor antagonists in offsetting or blocking such effects. A brief account of the current state of these mechanisms in at a cellular and tissue level forms the basis of this review.
Young
Morag J
MJ
Prince Henry's Institute of Medical Research and Baker Medical Research Institute, Melbourne, Australia. morag.young@med.monash.edu.au
Funder
John W
JW
D000450:Aldosterone / Q000502:physiology*; D000818:Animals; D006332:Cardiomegaly / Q000209:etiology / Q000503:physiopathology; D002319:Cardiovascular System / Q000503:physiopathology*; D006333:Heart Failure / Q000188:drug therapy; D006801:Humans; D006929:Hyperaldosteronism / Q000150:complications / Q000503:physiopathology; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use; D018161:Receptors, Mineralocorticoid / Q000502:physiology*; D013148:Spironolactone / Q000627:therapeutic use
D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; D000450:Aldosterone