Peroxynitrite-mediated vasorelaxation: evidence against the formation of circulating S-nitrosothiols.
Peroxynitrite-induced relaxation of isolated vessels may involve the formation of S-nitrosothiols. This study characterized the hemodynamic effects of systemically injected peroxynitrite in penotobarbital sodium-anesthetized rats and determined whether these effects were due to the formation of S-nitrosothiols. We utilized L-penicillamine, which attenuates the hemodynamic effects of systemically injected S-nitrosothiols. The hemodynamic effects of peroxynitrite and the S-nitrosothiols L-S-nitrosocysteine, L-S-nitrosoglutathione, and S-nitrosoalbumin were determined before and 25 min after the administration of L-penicillamine or saline. Peroxynitrite and the S-nitrosothiols produced dose-dependent reductions in mean arterial pressure and mesenteric and hindquarter vascular resistances. The hypotensive and vasodilator effects of the S-nitrosothiols were significantly reduced by L-penicillamine. In contrast, the hemodynamic actions of peroxynitrite were unaffected by L-penicillamine. Therefore, peroxynitrite produces hypotensive and vasodilator responses in anesthetized rats that are unlikely to be due to the formation of circulating S-nitrosothiols. The mechanisms by which peroxynitrite produces vasodilatation in vivo remain to be determined.
Graves
J E
JE
Department of Pediatrics, University of Iowa, Iowa City 52242, USA.
Lewis
S J
SJ
Kooy
N W
NW
D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D003545:Cysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D005978:Glutathione / Q000031:analogs & derivatives / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D008623:Mercaptoethanol; D009566:Nitrates / Q000494:pharmacology*; D009603:Nitroso Compounds / Q000494:pharmacology*; D010396:Penicillamine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D026422:S-Nitrosoglutathione; D026403:S-Nitrosothiols; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D009566:Nitrates; D009603:Nitroso Compounds; D026403:S-Nitrosothiols; C091665:S-nitrosoalbumin; C039642:peroxynitric acid; D012710:Serum Albumin, Bovine; D026422:S-Nitrosoglutathione; D008623:Mercaptoethanol; C032635:S-nitrosomercaptoethanol; C021315:S-nitrosocysteine; D005978:Glutathione; D010396:Penicillamine; D003545:Cysteine