Nitric oxide synthase inhibition results in immediate postoperative recovery of gastric, small intestinal and colonic motility in awake rats.
BACKGROUND
Nitric oxide (NO) is known to inhibit gastrointestinal motility. However, no detailed analysis of gastric, small intestinal and colonic motor effects, including effects on contraction frequency, has, as yet, been reported after NO inhibition in awake rats. We therefore investigated the effects of NO synthase inhibition on gastric, small intestinal and colonic motility in awake rats under baseline conditions and in a postoperative ileus model.


METHODS
In Sprague-Dawley rats, strain gauge transducers were sutured either to the gastric corpus, the small intestine or the colon. After 3 days, L-NMMA (NO synthase inhibitor), D-NMMA or vehicle was given i.v., while the motility was recorded continuously. In addition, postoperative gastric, small intestinal or colonic motility was investigated after L-NMMA or vehicle treatment prior to abdominal surgery. The motility index, the contraction amplitude, the area under the contraction amplitude and the contraction frequency were analysed.


RESULTS
L-NMMA decreased gastric motility to 60+/-8% for about 15 min, but continuously increased small intestinal motility to 221+/-22% and colonic motility to 125+/-7% compared to baseline (baseline=100%; p<0.01 for all comparisons). L-NMMA increased the contraction frequency throughout the gastrointestinal tract (stomach, 13+/-2%; small intestine, 8+/-1%; colon, 16+/-5%; p<0.01 vs. baseline for all comparisons). L-NMMA injection prior to surgery did not prohibit intraoperative inhibition of gastrointestinal motility, but did result in immediate recovery of gastric, small intestinal and colonic motility postoperatively (L-NMMA vs. vehicle, 0-60 min postoperatively; stomach, 90+/-9% vs. 53+/-3%; small intestine, 101+/-5% vs. 57+/-3%; colon, 134+/-6% vs. 60+/-5%; p<0.01 for all comparisons; no significant difference between preoperative baseline motility and L-NMMA treated rats postoperatively).


CONCLUSIONS
Under baseline conditions, endogenous NO inhibits small intestinal and colonic motility and gastric, small intestinal and colonic contraction frequency in awake rats. In the early postoperative period, endogenous NO is a major inhibitory component that seems to constitute the common final pathway of mediators and the neural pathways inhibiting gastrointestinal motility in rats.
Meile
T
T
Department of General and Transplantation Surgery, University Hospital, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany.
Glatzle
J
J
Habermann
F M
FM
Kreis
M E
ME
Zittel
T T
TT
D000818:Animals; D003106:Colon / Q000502:physiology*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology*; D045823:Ileus / Q000601:surgery; D007421:Intestine, Small / Q000502:physiology*; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D011184:Postoperative Period; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D013270:Stomach / Q000502:physiology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D019001:Nitric Oxide Synthase