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

Gastroenterology. 2000 Feb;118(2):316-27. doi: 10.1016/s0016-5085(00)70214-9.


Background & aims: We have shown that intestinal manipulation leads to a significant inhibition of circular muscle contraction. We hypothesized that the inflammatory mediator inducible nitric oxide (NO) plays a role in surgically induced ileus.

Methods: Rats and inducible NO synthase (iNOS) knockout and wild-type mice underwent a simple intestinal manipulation. Reverse-transcription polymerase chain reaction and immunohistochemistry were used to detect and localize iNOS expression. Nitrite and NO production were measured in muscularis cultures. Spontaneous and bethanechol-stimulated jejunal circular muscle contractions were measured in an organ bath.

Results: Intestinal manipulation resulted in significant iNOS messenger RNA induction in mucosa and muscularis. Immunohistochemistry localized iNOS in phagocytes within the muscularis. Nitrite and NO production increased 59.8-fold 24 hours after manipulation. L-n(6)-(1-iminoethyl) lysine (L-NIL) inhibited this response. In control rats, selective iNOS inhibition did not increase spontaneous muscle activity, but after manipulation L-NIL significantly improved spontaneous activity. iNOS knockout mice showed a significant 81% decrease in neutrophil infiltration into the muscularis after intestinal manipulation compared with wild-types. Contractile activity was normal in knockout mice after intestinal manipulation.

Conclusions: These results show that leukocyte-derived inducible NO inhibits gastrointestinal motility after manipulation and plays an essential role in the initiation of intestinal inflammation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bethanechol / pharmacology
  • Enzyme Inhibitors / pharmacology
  • In Vitro Techniques
  • Intestine, Small / physiology*
  • Intestine, Small / physiopathology
  • Intestine, Small / surgery*
  • Lysine / analogs & derivatives
  • Lysine / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle Contraction / drug effects
  • Muscle Contraction / physiology
  • Muscle, Smooth / physiology
  • Muscle, Smooth / physiopathology
  • Muscle, Smooth / surgery
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase / deficiency
  • Nitric Oxide Synthase / genetics
  • Nitric Oxide Synthase / metabolism*
  • Nitric Oxide Synthase Type II
  • Nitrites / metabolism
  • Phagocytes / enzymology
  • Rats
  • Rats, Inbred ACI


  • Enzyme Inhibitors
  • N(6)-(1-iminoethyl)lysine
  • Nitrites
  • Bethanechol
  • Nitric Oxide
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Nos2 protein, rat
  • Lysine