title: Prevention of endothelial dysfunction in heart failure by vitamin E: attenuation of vascular superoxide anion formation and increase in soluble guanylyl cyclase expression.
abstract: 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.
authors.affiliation: Medizinische Klinik der Julius-Maximilians-Universität Würzburg, Würzburg, Germany. j.bauersachs@medizin.uni-wuerzburg.de
authors.forename: J
authors.initials: J
authors.lastname: Bauersachs
authors.forename: I
authors.initials: I
authors.lastname: Fleming
authors.forename: D
authors.initials: D
authors.lastname: Fraccarollo
authors.forename: R
authors.initials: R
authors.lastname: Busse
authors.forename: G
authors.initials: G
authors.lastname: Ertl
mesh_terms: 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*
chemical_list: D000975:Antioxidants; D013481:Superoxides; D014810:Vitamin E; D006162:Guanylate Cyclase; D000109:Acetylcholine