Mineralocorticoid Receptor Antagonism Confers Cardioprotection in Heart Failure

• Published in: Current heart failure reports Vol. 10; no. 1; pp. 36 - 45
• Main Authors: Seawell, Michael R., Al Darazi, Fahed, Farah, Victor, Ramanathan, Kodangudi B., Newman, Kevin P., Bhattacharya, Syamal K., Weber, Karl T.
• Format: Journal Article
• Language: English
• Published: New York Current Science Inc 01.03.2013
• Subjects: Antioxidants - physiology; Cardiac Surgery; Cardiology; Cardiotonic Agents - therapeutic use; Heart Failure - drug therapy; Heart Failure - physiopathology; Humans; Imaging; Internal Medicine; Medicine; Medicine & Public Health; Mineralocorticoid Receptor Antagonists - therapeutic use; Neurotransmitter Agents - physiology; Oxidative Stress - physiology; Pharmacologic Therapy (WHW Tang; Radiology; Section Editor; Vascular Surgery; Zinc - physiology; Oxidative stress; Mitochondria; Cardioprotection; Calcium; Congestive heart failure; Magnesium; Antioxidant defenses; Potassium; Mineralocorticoid receptor antagonists; Zinc
• ISSN: 1546-9530; 1546-9549
• DOI: 10.1007/s11897-012-0120-x

The symptoms and signs constituting the congestive heart failure (CHF) syndrome have their pathophysiologic origins rooted in a salt-avid renal state mediated by effector hormones of the renin-angiotensin-aldosterone and adrenergic nervous systems. Controlled clinical trials, conducted over the past decade in patients having minimally to markedly severe symptomatic heart failure, have demonstrated the efficacy of a pharmacologic regimen that interferes with these hormones, including aldosterone receptor binding with either spironolactone or eplerenone. Potential pathophysiologic mechanisms, which have not hitherto been considered involved for the salutary responses and cardioprotection provided by these mineralocorticoid receptor antagonists, are reviewed herein. In particular, we focus on the less well-recognized impact of catecholamines and aldosterone on monovalent and divalent cation dyshomeostasis, which leads to hypokalemia, hypomagnesemia, ionized hypocalcemia with secondary hyperparathyroidism and hypozincemia. Attendant adverse cardiac consequences include a delay in myocardial repolarization with increased propensity for supraventricular and ventricular arrhythmias, and compromised antioxidant defenses with increased susceptibility to nonischemic cardiomyocyte necrosis.