title: Aldosterone as a mediator in cardiovascular injury.
abstract: The renin-angiotensin-aldosterone system plays a central role in the development of hypertension and the progression of end-organ damage. Although angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists can initially suppress plasma aldosterone, it is now well established that aldosterone escape may occur, whereby aldosterone levels return to or exceed baseline levels. The classic effects of aldosterone relate mainly to its action on epithelial cells to regulate water and electrolyte balance. However, blood pressure reduction or fluid loss could not account for the results of the Randomized Aldactone Evaluation Study, which showed that a low dose of spironolactone in addition to conventional therapy could decrease the overall risk of mortality by 30% among patients with severe congestive heart failure. The action of aldosterone at nonepithelial sites in the brain, heart, and vasculature is consistent with the presence of mineralocorticoid receptors in these tissues. Aldosterone has a number of deleterious effects on the cardiovascular system, including myocardial necrosis and fibrosis, vascular stiffening and injury, reduced fibrinolysis, endothelial dysfunction, catecholamine release, and production of cardiac arrhythmias. Several studies have now shown vascular and target-organ protective effects of aldosterone receptor antagonism in the absence of significant blood pressure lowering, consistent with a major role for endogenous mineralocorticoids as mediators of cardiovascular injury. The advent of selective aldosterone receptor antagonists such as eplerenone should prove of great therapeutic value in the prevention of cardiovascular disease and associated end-organ damage.
authors.affiliation: Department of Pharmacology, New York Medical College, Valhalla, New York 10595, USA.
authors.forename: Charles T
authors.initials: CT
authors.lastname: Stier
authors.forename: Praveen N
authors.initials: PN
authors.lastname: Chander
authors.forename: Ricardo
authors.initials: R
authors.lastname: Rocha
mesh_terms: D000450:Aldosterone / Q000097:blood / Q000502:physiology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000473:pathology; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002216:Captopril / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D005355:Fibrosis; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D012084:Renin-Angiotensin System; D013148:Spironolactone / Q000627:therapeutic use
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D009569:Nitric Oxide; D000450:Aldosterone; D002216:Captopril