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Efficacy of aldosterone receptor antagonism in heart failure: potential mechanisms.

Abstract
Results of the Randomized Aldactone Evaluation Study and the Eplerenone Post-acute Myocardial Infarction Heart Failure Efficacy and Survival Study indicate aldosterone receptor antagonism, together with angiotensin-converting enzyme inhibition and loop diuretics, is a most effective strategy in reducing risk for all-cause and cardiovascular-related mortality and morbidity in patients with symptomatic heart failure. Responsible mechanisms are likely multifactoral. As a circulating hormone, aldosterone has well-known endocrine properties that contribute to the pathophysiology of congestive heart failure. This includes Na+ resorption at the expense of K+ excretion in such tissues as kidneys, colon, sweat, and salivary glands. Mg2+ excretion at these sites is likewise enhanced by aldosterone, whereas adrenal aldosterone secretion is regulated by extracellular Mg2+. Other endocrine actions of aldosterone receptor-ligand binding include: a reduction in biologically active cytosolic-free Mg2+, with intracellular Ca2+ loading in nonepithelial cells such as peripheral blood mononuclear cells; its influence on endothelial cell function; and its central actions, including the choroid plexus, activity of the hypothalamic paraventricular nucleus, and autonomic nervous system. De novo generation of aldosterone within the cardiovasculature is recognized and findings suggest its auto/paracrine properties contribute to tissue repair. Each of these actions is interrupted by aldosterone receptor antagonism and therefore may contribute to its salutary response in heart failure.
AuthorsKarl T Weber
JournalCurrent heart failure reports (Curr Heart Fail Rep) Vol. 1 Issue 2 Pg. 51-6 (Jul 2004) ISSN: 1546-9530 [Print] United States
PMID16036025 (Publication Type: Journal Article, Review)
Chemical References
  • Angiotensin-Converting Enzyme Inhibitors
  • Diuretics
  • Mineralocorticoid Receptor Antagonists
  • Sulfonamides
  • Aldosterone
  • Sodium
  • Magnesium
  • Potassium
  • Calcium
Topics
  • Aldosterone (physiology)
  • Angiotensin-Converting Enzyme Inhibitors (therapeutic use)
  • Blood Vessels (physiology)
  • Calcium (metabolism)
  • Diuretics (therapeutic use)
  • Heart Failure (drug therapy, physiopathology)
  • Humans
  • Hyperaldosteronism (physiopathology)
  • Magnesium (metabolism)
  • Mineralocorticoid Receptor Antagonists (therapeutic use)
  • Potassium (metabolism)
  • Sodium (metabolism)
  • Sulfonamides

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