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

Heitham T. Hassoun, Norman W. Weisbrodt, David W. Mercer, Rosemary A. Kozar, Frank G. Moody, Frederick A. Moore

Research output: Contribution to journalArticlepeer-review

76 Scopus citations

Abstract

Inducible nitric oxide synthase (NOS 2) is thought to play a role in gut motility disorders that occur under proinflammatory conditions. Clinically, ileus occurs after sepsis and shock-induced gut ischemia/reperfusion (I/R). The purpose of this study was to determine if NOS 2 mediates impaired intestinal transit in well-established models of both moderate and severe gut ischemia/reperfusion. At laparotomy, Sprague-Dawley rats had duodenal catheters placed. Small intestinal transit was determined by quantitating the percentage tracer (FITC-dextran) in 10 equal segments of intestine 30 min after catheter injection [expressed as the mean geometric center (MGC) of distribution]. Transit was assessed at 6 and 24 h after gut ischemia [45 or 75 min of superior mesenteric artery occlusion (SMAO) with sham laparotomy as control]. In a separate set of experiments, N6-(iminoethyl)-L-lysine (L-NIL), a selective NOS 2 antagonist, was administered 1 h prior to laparotomy and transit was determined after 6 h as described above. Ileal NOS 2 expression 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 increased after 75, but not 45, min of SMAO. In addition, L-NIL improved transit after 75, but not 45, min of SMAO. We conclude that (1) NOS 2 is upregulated in the gut only after more severe ischemic insults, and (2) ileus is mediated, at least in part, by NOS 2 under these conditions.

Original languageEnglish (US)
Pages (from-to)150-154
Number of pages5
JournalJournal of Surgical Research
Volume97
Issue number2
DOIs
StatePublished - 2001

Keywords

  • Gut ischemia/reperfusion
  • Ileus
  • L-NIL
  • NOS 2

ASJC Scopus subject areas

  • Surgery

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