Inducible nitric oxide synthase mediates gut ischemia/reperfusion-induced ileus only after severe insults

Inducible nitric oxide synthase (NOS 2) is thought to play a role in gut mo tility disorders that occur under proinflammatory conditions. Clinically, i leus occurs after sepsis and shock-induced gut ischemia/ reperfusion (I/R). The purpose of this study was to determine if NOS 2 mediates impaired inte stinal transit in well-established models of both moderate and severe gut i schemia/reperfusion. At laparotomy, Sprague-Dawley rats had duodenal cathet ers placed. Small intestinal transit was determined by quantitating the per centage tracer (FITC-dextran) in 10 equal segments of intestine 30 min afte r catheter injection [expressed as the mean geometric center (MGC) of distr ibution]. Transit was assessed at 6 and 24 h after gut ischemia [45 or 75 m in of superior mesenteric artery occlusion (SMAO) with sham laparotomy as c ontrol]. In a separate set of experiments, N-6-(iminoethyl)L-lysine (L-NIL) , a selective NOS 2 antagonist, was administered 1 h prior to laparotomy an d transit was determined after 6 h as described above. Ileal NOS 2 expressi on was assessed by Western immunoblot and quantitative "real-time" RT-PCR. We observed that both 45 and 75 min of SMAO decreased intestinal transit at 6 h of reperfusion compared to sham. Ileal NOS 2 mRNA and protein were inc reased after 75, but not 45, min of SMAO. In addition, L-NIL improved trans it after 75, but not 45, min of SMAO. We conclude that (1) NOS 2 is upregul ated in the gut only after more severe ischemic insults, and (2) ileus is m ediated, at least in part, by NOS 2 under these conditions. (C) 2001 Academ ic Press.