title: Aldosterone induces electrical remodeling independent of hypertension.
abstract: BACKGROUND
  Treatment of heart failure patients with aldosterone antagonists has been shown to reduce the occurrence of sudden cardiac death. Therefore we aimed at determining the consequences of chronic exposure to aldosterone and the aldosterone antagonists eplerenone and spironolactone on the electrophysiological properties of the heart in a rat model.
  
  
  RESULTS
  Male Wistar rats were chronically treated (4weeks) with aldosterone (ALD) via an osmotic minipump. Spironolactone (SPI) or eplerenone (EPL) was administered with the rat chow. ALD treated animals developed left ventricular hypertrophy, prolonged QT-intervals, a higher rate of ventricular premature beats and non-sustained ventricular tachycardia despite normal blood pressure values. Spironolactone and eplerenone were both able to inhibit the alterations. Left-ventricular mRNA expressions of Kv4.2 and Kv4.3 (Ito), Kv1.5 (IKur), Kir2.1 and Kir2.3 (IK1) and of Cav1.2 (L-type Ca(2+) channel) were significantly down-regulated in ALD. Correspondingly, the protein expressions of subunits Kv1.5, Kir2.3 and Cav1.2 were significantly decreased. A diminished calcineurin activity and mRNA expression of the Aß subunit of calcineurin were found in ALD, which was insensitive to aldosterone antagonists.
  
  
  CONCLUSIONS
  Chronic aldosterone-overload induces blood pressure independent structural and electrical remodeling of the myocardium resulting in an increased risk for malignant ventricular arrhythmias.
authors.affiliation: Department of Internal Medicine III, University of Cologne, Cologne, Germany.
authors.forename: Theresa
authors.initials: T
authors.lastname: Dartsch
authors.forename: Robert
authors.initials: R
authors.lastname: Fischer
authors.forename: Andrej
authors.initials: A
authors.lastname: Gapelyuk
authors.forename: Marco
authors.initials: M
authors.lastname: Weiergraeber
authors.forename: Dennis
authors.initials: D
authors.lastname: Ladage
authors.forename: Toni
authors.initials: T
authors.lastname: Schneider
authors.forename: Alexander
authors.initials: A
authors.lastname: Schirdewan
authors.forename: Hannes
authors.initials: H
authors.lastname: Reuter
authors.forename: Jochen
authors.initials: J
authors.lastname: Mueller-Ehmsen
authors.forename: Carsten
authors.initials: C
authors.lastname: Zobel
mesh_terms: D000450:Aldosterone / Q000633:toxicity*; D000818:Animals; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017180:Tachycardia, Ventricular / Q000139:chemically induced* / Q000503:physiopathology*; D020257:Ventricular Remodeling / Q000187:drug effects* / Q000502:physiology*
chemical_list: D000450:Aldosterone