title: Vasodilator actions of the endothelium-derived relaxing factor L-S-nitrosocysteine in anaesthetized rats are markedly diminished by peroxynitrite.
abstract: The aim of the present study was to assess the effects of the potent oxidant and nitrating agent peroxynitrite on the haemodynamic actions of the endothelium-derived S-nitrosothiol L-S-nitrosocysteine. The haemodynamic actions of L-S-nitrosocysteine (12.5-100 nmol/kg, i.v.) were determined in pentobarbital-anaesthetized rats before and after the induction of tachyphylaxis to peroxynitrite achieved by giving 10 intravenous injections of a 10 micromol/kg dose. L-S-Nitrosocysteine elicited dose-dependent reductions in mean arterial blood pressure and in hindquarter and mesenteric vascular resistance. The L-S-nitrosocysteine-induced responses were substantially attenuated after administration of peroxynitrite. We have reported previously that nitric oxide-mediated vasodilation is not diminished after the induction of tachyphylaxis to peroxynitrite. Taken together, these findings support the concept that peroxynitrite reduces the vasodilator actions of L-S-nitrosocysteine via oxidation and/or nitration of putative membrane-bound S-nitrosothiol recognition sites.
authors.affiliation: Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, Georgia 30602-7389, USA.
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Graves
authors.forename: James N
authors.initials: JN
authors.lastname: Bates
authors.forename: Neil W
authors.initials: NW
authors.lastname: Kooy
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Lewis
mesh_terms: D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003545:Cysteine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects; D006834:Hydrazines / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D020030:Nitric Oxide Donors / Q000494:pharmacology; D030421:Peroxynitrous Acid / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D026403:S-Nitrosothiols / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D013618:Tachyphylaxis / Q000502:physiology; D014665:Vasodilator Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology*
chemical_list: C105785:1-hexanamine-6-(2-hydroxy-1-methyl-2-nitrosohydrazine)-N-methyl; D006834:Hydrazines; D020030:Nitric Oxide Donors; D026403:S-Nitrosothiols; D014665:Vasodilator Agents; D030421:Peroxynitrous Acid; C021315:S-nitrosocysteine; D003545:Cysteine