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Aldosterone induces electrical remodeling independent of hypertension

Item Type:Article
Title:Aldosterone induces electrical remodeling independent of hypertension
Creators Name:Dartsch, T. and Fischer, R. and Gapelyuk, A. and Weiergraeber, M. and Ladage, D. and Schneider, T. and Schirdewan, A. and Reuter, H. and Mueller-Ehmsen, J. and Zobel, C.
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. METHODS AND 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.
Keywords:Electrical Remodeling, Aldosterone, Hypertrophy, Sudden Cardiac Death, Animals, Rats
Source:International Journal of Cardiology
Page Range:170-178
Date:5 April 2013
Official Publication:https://doi.org/10.1016/j.ijcard.2011.06.100
PubMed:View item in PubMed

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