title: Effects of peroxynitrite on relaxation through the NO/sGC/cGMP pathway in isolated rat iliac arteries.
abstract: OBJECTIVE
  The present study investigated the mechanism by which peroxynitrite impairs vascular function through the nitric oxide (NO)/soluble guanylate cyclase (sGC)/cGMP pathway.
  
  
  METHODS
  Mechanical responses of rat external iliac arteries without endothelium were studied under exposure to peroxynitrite. cGMP concentrations were determined by enzyme immunoassay.
  
  
  RESULTS
  Relaxation induced by BAY 41-2272 (sGC stimulator) was impaired under exposure to peroxynitrite, whereas that by BAY 60-2770 (sGC activator) was enhanced. These responses were correlated with tissue levels of cGMP. Effects of peroxynitrite on the relaxant responses to BAY compounds were also observed in the presence of superoxide dismutase (SOD) or tempol, both of which scavenge a certain kind of reactive molecules other than peroxynitrite. As is the case with the relaxant response to BAY 41-2272, acidified NaNO2- and nitroglycerin-induced relaxations were markedly attenuated by exposing the arteries to peroxynitrite, which was not abolished by preincubation with SOD or tempol. On the other hand, peroxynitrite exposure had no effect on the 8-Br-cGMP-induced vasorelxation.
  
  
  CONCLUSIONS
  These findings suggest that peroxynitrite interferes with the NO/sGC/cGMP pathway by altering the redox state of sGC. It is likely that peroxynitrite can shift the sGC redox equilibrium to the NO-insensitive state in the vasculature.
authors: Department of Pharmacology, Shiga University of Medical Science, Otsu, Japan.
authors: Masashi
authors: M
authors: Tawa
authors: Takashi
authors: T
authors: Shimosato
authors: Hirotaka
authors: H
authors: Iwasaki
authors: Takeshi
authors: T
authors: Imamura
authors: Tomio
authors: T
authors: Okamura
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D020536:Enzyme Activators / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000378:metabolism*; D007083:Iliac Artery / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D010084:Oxidation-Reduction; D030421:Peroxynitrous Acid / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D015290:Second Messenger Systems / Q000187:drug effects; D000071756:Soluble Guanylyl Cyclase; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D020536:Enzyme Activators; D018160:Receptors, Cytoplasmic and Nuclear; D014665:Vasodilator Agents; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D006152:Cyclic GMP