LPS-induced muscularis macrophage nitric oxide suppresses rat jejunal circular muscle activity

Mark K. Eskandari, Jörg G. Kalff, Timothy R. Billiar, Kenneth K W Lee, Anthony J. Bauer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

146 Scopus citations

Abstract

Cellular mechanisms of sepsis-induced ileus remain an enigma. The study aim was to determine the role of nitric oxide (NO) in mediating the suppression of rat jejunal circular smooth muscle activity during endotoxemia. Isolated muscularis inducible NO synthase (iNOS) mRNA was measured by RT-PCR, immunohistochemistry was employed to localize iNOS protein, and contractile activity was measured in an organ bath. The low basal expression of muscularis iNOS mRNA expression was increased in a time- dependent fashion after lipopolysaccharide (LPS), resulting in a 20-fold increase over controls 3 h after injection. Immunohistochemistry of muscularis whole mounts and dissociated muscularis cells for iNOS revealed staining only in the muscularis macrophages 12 h after LPS. LPS caused a 68% reduction in spontaneous muscle activity 12 h after injection, which improved by 53% after the in vitro application of the selective iNOS inhibitor L-N6- (1-iminoethyl)lysine. Similar results were obtained in C57BL/6 mice but not in iNOS knockout mice. These data demonstrate that macrophage iNOS plays an important role in mediating LPS-induced intestinal circular muscle suppression.

Original languageEnglish (US)
Pages (from-to)G478-G486
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume277
Issue number2 40-2
DOIs
StatePublished - 1999

Keywords

  • Inducible nitric oxide
  • Lipopolysaccharide
  • Macrophage
  • Sepsis
  • Small intestine
  • Smooth muscle

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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