Hyporeactivity of mesenteric vascular bed in endotoxin-treated rats

Delia Mitolo-Chieppa, Miralma Serio, M. Assunta Potenza, Monica Montagnani, Gianfranco Mansi, Salvatore Pece, Emilio Jirillo, Jean Claude Stoclet

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Abstract

Vascular reactivity and activation of the nitric oxide (NO) pathway were investigated in perfused mesenteric vascular bed removed from rats 5 h after i.p. injection of bacterial lipopolysaccharide (E. coli lipopolysaccharide, 30 mg kg -1). Lipopolysaccharide treatment induced hyporesponsiveness to noradrenaline. Maximal noradrenaline-induced vasoconstriction was significantly reduced in lipopolysaccharide-treated vs. untreated preparations. Continuous infusion of L-arginine (L-Arg) (0.2 mM) enhanced noradrenaline hyporeactivity of lipopolysaccharide-treated rats. N(ω)-Nitro-L-arginine methyl ester (L-NAME) (0.2 mM), a non-selective inhibitor of NO synthase, failed to completely restore the noradrenaline hyporeactivity of lipopolysaccharide-treated + L-Arg-infused mesenteric vascular bed. After L-NAME treatment, Methylene blue (10 μM), a guanylate cyclase inhibitor, produced no additional increase of noradrenaline vasoconstriction in lipopolysaccharide-treated + L-Arg-infused mesenteric vascular bed, suggesting that an NO-independent activation of guanylate cyclase may be excluded. In lipopolysaccharide-treated preparations, L-Arg (0.2 mM) elicited a significant increase in nitrite production, which was antagonized by L-NAME. In conclusion, lipopolysaccharide-induced noradrenaline hyporesponsiveness of rat resistance vessels can only be partially explained by NO overproduction. Other mechanisms, probably related to vasoconstriction, may be involved.

Original languageEnglish
Pages (from-to)175-182
Number of pages8
JournalEuropean Journal of Pharmacology
Volume309
Issue number2
DOIs
Publication statusPublished - Aug 8 1996

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Keywords

  • L-Arginine
  • Lipopolysaccharide
  • Mesenteric vascular bed
  • Nitric oxide (NO)
  • Nitric oxide (NO) synthase
  • Rat
  • Septic shock

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Mitolo-Chieppa, D., Serio, M., Potenza, M. A., Montagnani, M., Mansi, G., Pece, S., Jirillo, E., & Stoclet, J. C. (1996). Hyporeactivity of mesenteric vascular bed in endotoxin-treated rats. European Journal of Pharmacology, 309(2), 175-182. https://doi.org/10.1016/0014-2999(96)00347-0