Loss of vascular responsiveness induced by endotoxin involves L-arginine pathway

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

Research output: Contribution to journalArticle

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Abstract

The involvement of L-arginine-dependent nitric oxide (NO) production in the vascular failure observed in endotoxemia was investigated in male Wistar rats treated with Escherichia coli lipopolysaccharide (LPS). Contractile responses to norepinephrine (NE) were measured ex vivo in aortas isolated from rats treated with LPS (20 mg/kg ip, 4 h before experiments) and pressor responses to NE were recorded in vivo in rats infused with LPS (5 mg·kg-1·h-1 iv). LPS pretreatment induced a rightward shift of the concentration-response curve to NE and a reduction of the maximal contraction by ~ 43% and 54% (P <0.05) in aortic rings with and without functional endothelium, respectively. This was not modified by the presence of indomethacin (10 μM) during the contractile experiments. In contrast, in the presence of N(G)-monomethyl-L-arginine (L-NMMA, 300 μM) or methylene blue (10 μM), maximal contractions to NE were restored to control values whether functional endothelium was present or not. The effects of L-NMMA were reversed by L- but not by D-arginine. Additionally, the effects of LPS pretreatment on vascular contractility were potentiated by L-arginine. In vivo, LPS infusion produced a reduction in pressor responsiveness to NE (0.1-10 mg/kg), which was also abolished by L-NMMA (30 mg/kg iv). This effect of L-NMMA was reversed by L- but not by D-arginine (100 mg/kg iv). These results demonstrate that activation of the L-arginine pathway has a major role in the production of vascular hyporeactivity in endotoxemia, ex vivo as well as in vivo. Additionally, they suggest that endothelium-independent vascular production of NO may be involved.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume259
Issue number4 28-4
Publication statusPublished - 1990

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Endotoxins
Blood Vessels
Lipopolysaccharides
Arginine
omega-N-Methylarginine
Norepinephrine
Endotoxemia
Endothelium
Nitric Oxide
Methylene Blue
Vascular Endothelium
Indomethacin
Aorta
Wistar Rats
Escherichia coli

Keywords

  • anesthetized rat
  • aortic rings
  • lipopolysaccharide
  • N(G)-monomethyl-L-arginine
  • norepinephrine

ASJC Scopus subject areas

  • Physiology

Cite this

Loss of vascular responsiveness induced by endotoxin involves L-arginine pathway. / Julou-Schaeffer, G.; Gray, G. A.; Fleming, I.; Schott, C.; Parratt, J.; Stoclet, J. C.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 259, No. 4 28-4, 1990.

Research output: Contribution to journalArticle

Julou-Schaeffer, G. ; Gray, G. A. ; Fleming, I. ; Schott, C. ; Parratt, J. ; Stoclet, J. C. / Loss of vascular responsiveness induced by endotoxin involves L-arginine pathway. In: American Journal of Physiology - Heart and Circulatory Physiology. 1990 ; Vol. 259, No. 4 28-4.
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