Abstract:
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.
journal_name
Gastroenterologyjournal_title
Gastroenterologyauthors
Kalff JC,Schraut WH,Billiar TR,Simmons RL,Bauer AJdoi
10.1016/s0016-5085(00)70214-9keywords:
subject
Has Abstractpub_date
2000-02-01 00:00:00pages
316-27issue
2eissn
0016-5085issn
1528-0012pii
S0016508500418536journal_volume
118pub_type
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