L-β,β-Dimethylcysteine attenuates the haemodynamic responses elicited by systemic injections of peroxynitrite in anaesthetized rats

Jonathan E. Graves, Neil W. Kooy, Stephen J. Lewis

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4 Scopus citations

Abstract

1 There is direct chemical evidence that L-β,β-dimethylcysteine (L-penicillamine (L-PEN)) is a scavenger of peroxynitrite. The aim of this study was to determine whether L-PEN attenuates the haemodynamic responses elicited by peroxynitrite in pentobarbital-anaesthetized rats. 2 Peroxynitrite (1-20 μmol kg -1, i.v.) elicited dose-dependent reductions in mean arterial blood pressure (MAP) and mesenteric and hindquarter vascular resistances. 3 L-PEN (2 mmol kg -1, i.v.) elicited relatively minor but significant increases in MAP and vascular resistances. The initial reductions in MAP and vascular resistances elicited by peroxynitrite were not diminished after administration of L-PEN whereas they were much shorter in duration. As such, the total reductions in MAP and vascular resistances were markedly reduced by L-PEN. 4 The finding that L-PEN (2 mmol kg -1, i.v.) did not affect the hypotensive or vasodilator responses elicited of the ATP-dependent potassium-channel agonist, cromakalim (3-18 μg kg -1, i.v.), suggests that this dose of L-PEN is not a nonselective inhibitor of vasodilation. 5 These findings suggest that L-PEN may effectively scavenge peroxynitrite in vivo and/or interfere with the mechanisms by which peroxynitrite elicits its vasodilator responses.

Original languageEnglish (US)
Pages (from-to)7-15
Number of pages9
JournalBritish Journal of Pharmacology
Volume148
Issue number1
DOIs
StatePublished - May 2006

Keywords

  • Anaesthetized rats
  • Haemodynamics
  • L-penicillamine
  • Peroxynitrite, nitric oxide (NO)

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