Effect of L-NAME on decreased ileal muscle contractility induced by peritonitis in rats
Background/Purpose: It is now well established that intestinal inflammation is associated with disturbed contractility. The aim of this study was to determine the effects of peritonitis on longitudinal ileum smooth muscle responses to KCl, carbachol and substance P (SP) and to examine the role of nitric oxide (NO) and N-omega-nitro-L-arginine methylester (L-NAME) on ileal contractility in this peritonitis model. Methods: Peritonitis was induced by cecal ligation and puncture (CLP) in 20 rats. While 10 of these received 1 mL distilled water as placebo, the other 10 received 5 mg/kg (subcutaneously) L-NAME before the operation. Another group of 10 rats underwent a sham operation. Twenty-four hours after the operation, the rats were killed, and their ileum was excised. Ileum segments were placed in longitudinal direction in a 10-mL organ bath; concentration-response relationship for KCl, carbachol, and SP were obtained by adding the reagent cumulatively to the bath. Results: The KCl-, carbachol-, and SP-induced contractions were decreased markedly, with no change in the pD(2) values in the peritonitis group compared with controls. Peritonitis-induced changes in the contractile responses were restored significantly by in Vivo L-NAME pretreatment. Conclusions: The model of CLP-induced peritonitis in rats showed that KCl-induced non receptor-mediated, carbachol- and SP-induced receptor-mediated contractions are significantly decreased by inflammation in the longitudinal ileum muscle. Increased synthesis of NO may be responsible for these decreases in contractile responses because they were restored significantly by in Vivo L-NAME injection. Inhibition of NOS with L-NAME injection may afford a new therapeutic approach to the treatment of gastrointestinal stasis in septic patients.