Mechanisms of peroxynitrite-induced vasodilation in vivo

J. E. Graves, S. J. Lewis, N. W. Kooy

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3 Scopus citations

Abstract

Peroxynitrite is the product of the reaction between nitric oxide and superoxide anion. In vitro evidence suggests that the vasorelaxant effects of peroxynitrite may be due to formation of S-nitrosothiols. L-penicillamine (L-PEN) is an inhibitor of the hemodynamic effects of S-nitrosothiols such as L-S-nitrosocysteine (L-SNC). In this study, we used L-PEN (500 μmol/kg, i.v.) and the ATP-dependent K+-channel blocker glibenclamide (GLIB, 40 μmol/kg, i.v.) to investigate the mechanisms of peroxynitrite- and L-SNC-induced vasodilation in anesthetized rats. L-SNC and peroxynitrite produced dose-dependent reductions in mean arterial pressure (MAP) and mesenteric and hindquarter vascular resistances. L-PEN attenuated the peak hemodynamic responses of L-SNC (12.5 - 200 nmol/kg, i.V.). For example, the falls in MAP produced by 200 nmol/kg of L-SNC before and after L-PEN were -50 ±3% and -21 ±3% (P < 0.05). L-PEN also reduced the total hypotensive response as measured by area under the curve (AUC) (316 ± 43 and 85 ± 43 AUC units, pre- and post- L-PEN, P < 0.05). In contrast, L-PEN failed to alter the peak hemodynamic effects of peroxynitrite (0.5 - 10 μmol/kg, i.V.). For example, the peak falls in MAP produced by 10 μmol/kg peroxynitrite before and after L-PEN were -46 ±2% and -44 ±2% (P > 0.05). The total hypotensive response produced by peroxynitrite was also unaffected by L-PEN. GLIB inhibited the peak hemodynamic responses of peroxynitrite but did not affect those of L-SNC. These data suggest that the hemodynamic effects of peroxynitrite (i) do not involve the formation of S-nitrosothiols, and (ii) involve the activation of ATP-dependent K+-channels.

Original languageEnglish (US)
Pages (from-to)A456
JournalFASEB Journal
Volume11
Issue number3
StatePublished - Dec 1 1997

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