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.

Strain gauge transducer technique for investigation of the pathophysiology of postoperative colonic ileus in awake rats.

Postoperative inhibition of colonic motility is a major contributor to postoperative ileus, but only limited information is available on its pathophysiology. We developed a model to record perioperative gastrointestinal motility in awake rats and investigated the effect of nitric oxide (NO) synthesis blockade on postoperative colonic ileus in rats. Rats were equipped with an i.v. catheter. Two strain gauge transducers were sutured to the colon, and the effects of NO synthesis blockade on postoperative colonic motility were investigated. NO synthesis blockade slightly increased baseline colonic motility. Abdominal surgery profoundly inhibited colonic motility. Blockade of NO synthesis did not prohibit intraoperative inhibition of colonic motility, but significantly hastened recovery of postoperative colonic ileus compared to vehicle. We established a model to record gastric, small intestinal and colonic motility in awake rats postoperatively. Laparotomy and short manipulation of the cecum produced a prolonged inhibition of colonic motility. Inhibition of NO synthesis improved recovery of postoperative colonic motility, indicating that NO partly mediates postoperative colonic ileus in rats.