The pathophysiology of aldosterone in the cardiovascular system.
Until relatively recently, the mineralocorticoid hormone aldosterone was thought to be produced uniquely in the adrenal cortex and to act exclusively on epithelia to promote sodium retention and potassium excretion. However, it is now known that aldosterone also acts on nonepithelial tissues, such as brain, heart, and blood vessels, and that enzymes required for aldosterone biosynthesis are expressed in these same tissues, which may be consistent with local aldosterone production acting in a paracrine fashion. A number of studies indicate that aldosterone exerts clearly deleterious effects when levels are inappropriate for salt status. For example, aldosterone in a high-salt environment initiates a vascular inflammation response that leads to cardiac and vascular pathologies. In experimental models of hypertension and heart failure, the nonepithelial effects of aldosterone are mediated via classical mineralocorticoid receptors, and are largely or completely abolished by administration of the selective aldosterone blocker eplerenone or by reduction of circulating aldosterone by adrenalectomy. In the present manuscript, we review some of the most recent discoveries in the field of aldosterone biology, with special emphasis on the mechanisms involved in the deleterious actions of this mineralocorticoid in cardiovascular tissues.
Rocha
Ricardo
R
Global Medical Affairs, Pharmacia Corporation, 100 Route 206 North, PO Box 800, Peapack, New Jersey, USA. rrroch@pharmacia.com
Funder
John W
JW
D000450:Aldosterone / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D000077545:Eplerenone; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D009206:Myocardium / Q000473:pathology; D016032:Randomized Controlled Trials as Topic; D012492:Salts / Q000378:metabolism / Q000494:pharmacology; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D000451:Mineralocorticoid Receptor Antagonists; D012492:Salts; D013148:Spironolactone; D000450:Aldosterone; D000077545:Eplerenone