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.
journal_name
Int J Cardioljournal_title
International journal of cardiologyauthors
Dartsch T,Fischer R,Gapelyuk A,Weiergraeber M,Ladage D,Schneider T,Schirdewan A,Reuter H,Mueller-Ehmsen J,Zobel Cdoi
10.1016/j.ijcard.2011.06.100subject
Has Abstractpub_date
2013-04-05 00:00:00pages
170-8issue
2eissn
0167-5273issn
1874-1754pii
S0167-5273(11)00640-1journal_volume
164pub_type
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