Role of inducible nitric oxide synthase in postoperative intestinal smooth muscle dysfunction in rodents

J C Kalff1, W H Schraut, T R Billiar

  • 1Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15261, USA.

Gastroenterology
|January 29, 2000
PubMed
Abstract

Insights

Surgically induced ileus is inhibited by leukocyte-derived inducible nitric oxide (NO). This inflammatory mediator plays a key role in reducing gastrointestinal motility and initiating intestinal inflammation after manipulation.

Area of Science:

  • Gastroenterology
  • Immunology
  • Molecular Biology

Background:

  • Intestinal manipulation causes significant inhibition of circular muscle contraction.
  • Surgically induced ileus is a common clinical complication.
  • The role of inflammatory mediators in post-operative ileus is not fully understood.

Purpose of the Study:

  • To investigate the role of inducible nitric oxide (NO) in surgically induced ileus.
  • To determine the effect of inducible NO synthase (iNOS) on gastrointestinal motility.
  • To elucidate the involvement of iNOS in the inflammatory response following intestinal manipulation.

Main Methods:

  • Intestinal manipulation in rats and iNOS knockout/wild-type mice.
  • Detection and localization of iNOS expression using RT-PCR and immunohistochemistry.
  • Measurement of nitrite and NO production in muscularis cultures.
  • Assessment of jejunal circular muscle contractions in an organ bath.

Main Results:

  • Intestinal manipulation significantly induced iNOS mRNA in the mucosa and muscularis.
  • iNOS was localized in phagocytes within the muscularis, with a 59.8-fold increase in nitrite and NO production post-manipulation.
  • Selective iNOS inhibition improved spontaneous muscle activity in manipulated rats.
  • iNOS knockout mice exhibited reduced neutrophil infiltration and normal contractile activity after manipulation.

Conclusions:

  • Leukocyte-derived inducible NO inhibits gastrointestinal motility post-intestinal manipulation.
  • Inducible NO plays an essential role in initiating intestinal inflammation after surgical procedures.
  • Targeting iNOS may offer a therapeutic strategy for managing post-operative ileus.