© 2003 by European Society of Cardiology
Copyright © 2003, European Society of Cardiology
Addition of the selective aldosterone receptor antagonist eplerenone to ACE inhibition in heart failure: effect on endothelial dysfunction
aMedizinische Klinik der Julius-Maximilians-Universität Würzburg, Josef-Schneider-Str. 2, D-97080 Würzburg, Germany
bPharmacia Corp., Peapack, NJ, USA
cKlinik für Anaesthesiologie der Julius-Maximilians-Universität Würzburg, Würzburg, Germany
bauersachs_j{at}medizin.uni-wuerzburg.de
* Corresponding author. Tel.: +49-931-2011; fax: +49-931-2013-6302.
Objectives: To investigate the effects of adding the selective aldosterone receptor antagonist eplerenone to ACE inhibition on endothelium-dependent vasodilation in rats with chronic heart failure (CHF). Background: Addition of the non-selective aldosterone antagonist spironolactone to ACE-inhibitors reduces mortality and morbidity in CHF and improves endothelial vasomotor dysfunction, but is associated with considerable side-effects. Methods: Starting 10 days after extensive myocardial infarction (MI) or sham-operation, Wistar rats were treated either with placebo, the ACE inhibitor trandolapril (TR, 0.3 mg/kg body weight per day), the selective aldosterone receptor antagonist eplerenone (EPL, 100 mg/kg per day) or a combination of both for 9 weeks. Results: Maximum acetylcholine-induced, nitric oxide-dependent relaxation was significantly attenuated in aortic rings from rats with CHF compared with sham-operated animals (Rmax 55% vs. 87%). EPL alone slightly and TR significantly improved NO-mediated relaxation (CHF-EPL 66%; CHF-TR: 78%), while treatment with both EPL and TR completely restored endothelium-dependent vasorelaxation (CHF-EPL-TR: 83%). Aortic superoxide formation was significantly increased in rats with CHF compared with sham-operated animals, but was normalised by treatment with EPL or TR-EPL. Expression of the endothelial nitric oxide synthase was decreased in CHF and normalised in all treatment groups. Conclusions: In experimental CHF, the selective aldosterone antagonist EPL reduced the increased vascular superoxide formation. Although a combination of TR and EPL normalised endothelium-dependent relaxation, ACE inhibition as a monotherapy was almost equally effective.
KEYWORDS Endothelial function; Myocardial infarction; Heart failure; ACE inhibitors; Aldosterone
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