© 2001 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
Prevention of endothelial dysfunction in heart failure by vitamin E
Attenuation of vascular superoxide anion formation and increase in soluble guanylyl cyclase expression
aMedizinische Klinik der Julius-Maximilians-Universität Würzburg, Würzburg, Germany
bInstitut für Kardiovaskuläre Physiologie, Klinikum der J.W. Goethe-Universität, Frankfurt am Main, Germany
* Corresponding author. Medizinische Universitätsklinik, Josef-Schneider-Str. 2, D-97080 Würzburg, Germany. Tel.: +49-931-201-5301; fax: +49-931-201-5302 j.bauersachs{at}medizin.uni-wuerzburg.de
Objectives: Enhanced vascular superoxide anion generation contributes to endothelial dysfunction in heart failure. However, the effect of long-term treatment with the antioxidant vitamin E is unknown. Methods and Results: Relaxant responses were determined in aortic rings from Wistar rats with heart failure 12 weeks after myocardial infarction (MI) and compared with responses in tissues from sham-operated animals. From the seventh post-operative day, rats were given either a standard chow or a chow enriched in vitamin E (approximate intake 100 mg/day). In rings from rats with heart failure, acetylcholine-induced relaxation was attenuated (maximum relaxation, Rmax 54±3%) when compared with rings from sham-operated animals (79±3%, n=12, P<0.01), while endothelium-independent relaxation elicited by sodium-nitroprusside was unchanged. Aortic superoxide generation was significantly enhanced in rats with heart failure. Vitamin E supplementation significantly improved acetylcholine-induced relaxation in rats with heart failure (Rmax 75±4%, P<0.01) and led to a leftward shift in sodium-nitroprusside-induced relaxation curve. Aortic expression of the β1-subunit of soluble guanylyl cyclase was significantly enhanced by vitamin E supplementation. In addition, the elevated vascular superoxide formation was normalised by vitamin E. Conclusions: These results demonstrate that dietary supplementation with the antioxidant vitamin E restores normal endothelial function, reduces vascular superoxide anion formation and increases the expression of the soluble guanylyl cyclase in rats with heart failure.
KEYWORDS Endothelial function; Free radicals; Heart failure; Vasoconstriction/dilation; Nitric oxide
Presented in part at the 72nd Scientific Sessions of the American Heart Association, Atlanta, GA, USA, November 7–10, 1999, and published in abstract form (Circulation 100, Suppl I, 1999, I-757).
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