Prevention of endothelial dysfunction in heart failure by vitamin E: attenuation of vascular superoxide anion formation and increase in soluble guanylyl cyclase expression.
OBJECTIVE
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.


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, R(max) 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 (R(max) 75 +/- 4%, P < 0.01) and led to a leftward shift in sodium-nitroprusside-induced relaxation curve. Aortic expression of the beta(1)-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.
Bauersachs
J
J
Medizinische Klinik der Julius-Maximilians-Universität Würzburg, Würzburg, Germany. j.bauersachs@medizin.uni-wuerzburg.de
Fleming
I
I
Fraccarollo
D
D
Busse
R
R
Ertl
G
G
D000109:Acetylcholine; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D006162:Guanylate Cyclase / Q000378:metabolism; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects; D014810:Vitamin E / Q000627:therapeutic use*
D000975:Antioxidants; D013481:Superoxides; D014810:Vitamin E; D006162:Guanylate Cyclase; D000109:Acetylcholine