Review of aldosterone- and angiotensin II-induced target organ damage and prevention.
Aldosterone is well recognized as a cause of sodium reabsorption, water retention, and potassium and magnesium loss; however, it also produces a variety of other actions that lead to progressive target organ damage in the heart, vasculature, and kidneys. Aldosterone interacts with mineralocorticoid receptors to promote endothelial dysfunction, facilitate thrombosis, reduce vascular compliance, impair baroreceptor function, and cause myocardial and vascular fibrosis. Although angiotensin II has been considered the major mediator of cardiovascular damage, increasing evidence suggests that aldosterone may mediate and exacerbate the damaging effects of angiotensin II. While angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers reduce plasma aldosterone levels initially, aldosterone rebound, or 'escape' may occur during long-term therapy. Therefore, aldosterone blockade is required to reduce the risk of progressive target organ damage in patients with hypertension and heart failure. This may be achieved nonselectively with spironolactone or with use of the selective aldosterone blocker eplerenone. While both agents have been demonstrated to be effective antihypertensive agents, eplerenone may produce improved target organ protection as witnessed in a variety of clinical settings, without the antiandrogenic and progestational effects commonly observed with spironolactone.
Department of Clinical Pharmacology and Therapeutics, Ninewells Hospital and Medical School, Tayside DD1 9SY, Dundee, UK. a.d.struthers@dundee.ac.uk
Allan D
AD
Struthers
Thomas M
TM
MacDonald
D000450:Aldosterone / Q000502:physiology*; D000804:Angiotensin II / Q000502:physiology*; D057912:Angiotensin II Type 2 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D000077545:Eplerenone; D006801:Humans; D007668:Kidney / Q000378:metabolism; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use; D009206:Myocardium / Q000378:metabolism*; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000627:therapeutic use
D057912:Angiotensin II Type 2 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000451:Mineralocorticoid Receptor Antagonists; D000804:Angiotensin II; D013148:Spironolactone; D000450:Aldosterone; D000077545:Eplerenone