Role of ATP-sensitive K+-channels in hemodynamic effects of peroxynitrite in anesthetized rats

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

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

The aim of this study was to determine whether the hypotensive and vasodilator actions of peroxynitrite in pentobarbital-anesthetized rats involve the activation of ATP-sensitive K+-channels (K+ ATP-channels). The effects of the K+ATP-channel agonist, cromakalim (9-36 μg/kg, iv), peroxynitrite (0.5-10 μmol/kg iv), and L-S-nitrosocysteine (12.5-200 nmol/kg, iv) on mean arterial blood pressure (MAP) and mesenteric (MR) and hindquarter (HQR) vascular resistances were determined before and after injection of the K+ATP-channel blocker, glibenclamide (40 μmol/kg, iv). Cromakalim, peroxynitrite, and L-S-nitrosocysteine produced dose-dependent reductions in MAP, MR, and HQR. Administration of glibenclamide did not affect resting hemodynamic parameters but markedly attenuated the hemodynamic actions of cromakalim. The maximal falls in MAP and HQR produced by peroxynitrite were attenuated by glibenclamide whereas the maximal falls in MR were not affected. In addition, the duration of the hypotensive and vasodilator effects of peroxynitrite in the mesenteric and hindquarter beds were markedly diminished by glibenclamide. In contrast, glibenclamide did not affect the maximal hypotensive or vasodilator effects of L-S-nitrosocysteine or the duration of these responses. These results suggest that the hypotensive and vasodilator actions of peroxynitrite in anesthetized rats involve the activation of K+ATP-channels whereas the hemodynamic actions of L-S-nitrosocysteine do not.

Original languageEnglish (US)
Pages (from-to)653-659
Number of pages7
JournalJournal of Cardiovascular Pharmacology
Volume46
Issue number5
DOIs
StatePublished - Nov 2005

Keywords

  • Cromakalim
  • Glibenclamide
  • Nitric oxide
  • S-nitrosothiols
  • Vasodilation

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