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Updated: Jul 11, 2026

Functional Assessment of Intestinal Motility and Gut Wall Inflammation in Rodents: Analyses in a Standardized Model of Intestinal Manipulation
Published on: September 11, 2012
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.
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.
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.
Related Concept Videos
Nitric Oxide Signaling Pathway
Intestinal Obstruction II: Pathophysiology

