Vasodilator actions of the endothelium-derived relaxing factor L-S-nitrosocysteine in anaesthetized rats are markedly diminished by peroxynitrite

Jonathan E. Graves, James N. Bates, Neil W. Kooy, Stephen J. Lewis

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

1. 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. 2. 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 μmol/kg dose. 3. l-S-Nitrosocysteine elicited dose-dependent reductions in mean arterial blood pressure and in hindquarter and mesenteric vascular resistance. 4. The l-S-nitrosocysteine-induced responses were substantially attenuated after administration of peroxynitrite. 5. 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.

Original languageEnglish (US)
Pages (from-to)1137-1141
Number of pages5
JournalClinical and Experimental Pharmacology and Physiology
Volume32
Issue number12
DOIs
StatePublished - Dec 1 2005

Keywords

  • L-S-nitrosocysteine
  • Nitric oxide
  • Peroxynitrite
  • Rat
  • Tachyphylaxis
  • Vasodilation

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