Peroxynitrite-mediated attenuation of α- and β-adrenoceptor agonist-induced vascular responses in vivo

Nancy A. Benkusky, Stephen J. Lewis, Neil W. Kooy

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

Peroxynitrite is produced by vascular endothelial and smooth muscle cells in response to inflammation, induces vascular relaxation, and alters vascular responses to endothelial-derived relaxing factors. The present study examined the changes in mean arterial pressure and hindquarter, renal, and mesenteric vascular resistances produced by the systemic administration of (i) the catecholamines epinephrine or norepinephrine, (ii) the α1-adrenoceptor agonist phenylephrine, (iii) the β-adrenoceptor agonist isoproterenol or (iv) [Argδ] vasopressin in pentobarbital-anesthetized rats prior to and following the systemic administration of peroxynitrite. The systemic administration of peroxynitrite significantly inhibited (i) epinephrine-induced pressor and renal and mesenteric vasoconstrictor responses, (ii) norepinephrine-induced pressor and hindquarter, renal, and mesenteric vasoconstrictor responses, (iii) phenylephrine-induced hindquarter and mesenteric vasoconstrictor responses, and (iv) isoproterenol-induced depressor and hindquarter and renal vasodilator responses. In comparison, the systemic administration of peroxynitrite had no effect on arginine vasopressin-induced pressor or vasoconstrictor responses. These results demonstrate selective and consequential attenuation of the hemodynamic effects produced by α- and β-adrenoceptor agonists, suggesting that selective impairment of adrenoceptors by peroxynitrite may play a critical role in the hemodynamic dysfunction associated with inflammatory conditions. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)151-158
Number of pages8
JournalEuropean Journal of Pharmacology
Volume364
Issue number2-3
DOIs
StatePublished - Jan 8 1999

Keywords

  • Catecholamines
  • Hemodynamics
  • Nitric oxide (NO)
  • Peroxynitrite
  • Superoxide

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