Activation of the L-arginine-nitric oxide pathway is involved in vascular hyporeactivity induced by endotoxin

G. Julou-Schaeffer, G. A. Gray, I. Fleming, C. Schott, J. R. Parratt, J. C. Stoclet

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37 Citations (Scopus)

Abstract

The possible implication of a nitric oxide (NO)-like relaxing substance in endotoxin-induced vascular hyporeactivity to norepinephrine (NA) was investigated in rats, under three different experimental conditions: ex vivo in aortic rings removed from rats injected with E. coli endotoxin lipopolysaccharide (LPS, 20 mg/kg i.p.), in vitro in aortic rings incubated with LPS (100 ng/ml) for 5 h, and in vivo on pressure responsiveness in rats infused with LPS (5 mg/kg/h, 50 min). In all conditions, responses to NA were reduced by LPS. Both ex vivo and in vitro, this effect was observed whether functional endothelium was present or not, it was increased by L- but not D-arginine, and it was associated with a three- to fourfold increase in cyclic GMP content. Addition of methylene blue (2 μM), a guanylate cyclase inhibitor, restored NA-induced contraction. In all cases, inhibitors of NO formation from L-arginine abolished LPS-induced hyporeactivity to NA. These results suggest that increased NO production in blood vessels underlies hyporeactivity to NA in endotoxemia.

Original languageEnglish
Pages (from-to)S207-S212
JournalJournal of cardiovascular pharmacology
Volume17
Issue numberSUPPL. 3
Publication statusPublished - Jan 1 1991

Keywords

  • Endotoxin
  • L-arginine
  • NO-production inhibitors
  • Nitric oxide
  • Norepinephrine
  • Vascular reactivity

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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    Julou-Schaeffer, G., Gray, G. A., Fleming, I., Schott, C., Parratt, J. R., & Stoclet, J. C. (1991). Activation of the L-arginine-nitric oxide pathway is involved in vascular hyporeactivity induced by endotoxin. Journal of cardiovascular pharmacology, 17(SUPPL. 3), S207-S212.