title: Mineralocorticoid receptor antagonism confers cardioprotection in heart failure.
abstract: 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.
authors.affiliation: Division of Cardiovascular Diseases, University of Tennessee Health Science Center, 956 Court Ave., Suite A312, Memphis, TN 38163, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Seawell
authors.forename: Fahed
authors.initials: F
authors.lastname: Al Darazi
authors.forename: Victor
authors.initials: V
authors.lastname: Farah
authors.forename: Kodangudi B
authors.initials: KB
authors.lastname: Ramanathan
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Newman
authors.forename: Syamal K
authors.initials: SK
authors.lastname: Bhattacharya
authors.forename: Karl T
authors.initials: KT
authors.lastname: Weber
mesh_terms: D000975:Antioxidants / Q000502:physiology; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D018377:Neurotransmitter Agents / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D015032:Zinc / Q000502:physiology
chemical_list: D000975:Antioxidants; D002316:Cardiotonic Agents; D000451:Mineralocorticoid Receptor Antagonists; D018377:Neurotransmitter Agents; D015032:Zinc