Gastric nitric oxide synthase expression during endotoxemia: Implications in mucosal defense in rats

Kenneth S. Helmer, Sonlee D. West, Gregory L. Shipley, Lily Chang, Yan Cui, David Mailman, David W. Mercer

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Background & Aims: This study was performed to examine expression of gastric nitric oxide synthase (NOS) isoforms during endotoxemia in rats and to assess their role(s) in gastric injury from bile and ethanol. Methods: Lipopolysaccharide (LPS) enhanced the expression and activity of inducible nitric oxide synthase in gastric mucosa in a dose- and time-dependent manner. Results: Endothelial nitric oxide synthase and neural nitric oxide synthase expression did not significantly change, but constitutive nitric oxide synthase activity decreased over time. LPS alone caused injury to the gastric mucosa and disrupted F-actin filaments in the same cells with enhanced immunostaining for inducible nitric oxide synthase. LPS also exacerbated gastric injury from the mild irritants 5 mmol/L acidified taurocholate and 20% ethanol as did local intra-arterial infusion of the nitric oxide donor S-nitroso-N-acetyl-penicillamine. The selective inducible nitric oxide synthase inhibitor aminoguanidine negated LPS-induced exacerbation of gastric injury from these irritants. The nonselective NOS inhibitor NG-nitro-L-arginine methyl ester augmented the deleterious effects of LPS, an effect reversed by L-arginine but not D-arginine. Aminoguanidine, but not NG-nitro-L-arginine methyl ester, negated LPS-induced accumulation of gastric luminal nitrates. Conclusions: These data suggest that increased inducible NOS activity and decreased constitutive nitric oxide synthase activity are primarily responsible for exacerbating gastric injury from luminal irritants during endotoxemia. Moreover, septic patients may be more susceptible to gastric injury from bile during gastrointestinal ileus.

Original languageEnglish (US)
Pages (from-to)173-186
Number of pages14
JournalGastroenterology
Volume123
Issue number1
DOIs
StatePublished - 2002

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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