Inducible nitric oxide synthase plays a critical role in resolving intestinal inflammation

Gastroenterology. 1997 Mar;112(3):1022-7. doi: 10.1053/gast.1997.v112.pm9041266.


Background & aims: Overproduction of nitric oxide by inducible nitric oxide synthase (iNOS) has been proposed as a pathogenic factor in colitis. The objective of this study was to examine the role of iNOS using iNOS-deficient mice in experimental colitis.

Methods: Colitis was induced by intrarectal instillation of 3% acetic acid and assessed for neutrophilic infiltration and intestinal injury over 7 days. iNOS messenger RNA expression was also measured.

Results: At 24 hours, acetic acid induced a mild colitis in wild-type mice. An increase in neutrophil infiltration and tissue edema was also observed. In the iNOS-deficient mice, a twofold increase in macroscopic damage was observed. Neutrophil infiltration and tissue edema were similar to those in wild-type animals at this time point. Although inflammation in wild-type mice had resolved by 7 days, a sevenfold increase in damage score and elevated myeloperoxidase level were still evident in iNOS-deficient mice. A striking increase in the message for iNOS was observed in inflamed wild-type mice at 24 hours and was still present at 72 hours. No message was found in iNOS-deficient mice.

Conclusions: Induction of iNOS seems to be a critical protective response to injury in intestinal inflammation possibly by reducing leukocytic infiltration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colitis / etiology*
  • Enzyme Induction
  • Female
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nitric Oxide Synthase / deficiency
  • Nitric Oxide Synthase / genetics
  • Nitric Oxide Synthase / physiology*
  • Peroxidase / metabolism
  • RNA, Messenger / analysis


  • RNA, Messenger
  • Peroxidase
  • Nitric Oxide Synthase