title: Gastric nitric oxide synthase expression during endotoxemia: implications in mucosal defense in rats.
abstract: OBJECTIVE
  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 N(G)-nitro-L-arginine methyl ester augmented the deleterious effects of LPS, an effect reversed by L-arginine but not D-arginine. Aminoguanidine, but not N(G)-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.
authors.affiliation: Department of Surgery, University of Texas Medical School, Houston, Texas 77026, USA.
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Helmer
authors.forename: Sonlee D
authors.initials: SD
authors.lastname: West
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Shipley
authors.forename: Lily
authors.initials: L
authors.lastname: Chang
authors.forename: Yan
authors.initials: Y
authors.lastname: Cui
authors.forename: David
authors.initials: D
authors.lastname: Mailman
authors.forename: David W
authors.initials: DW
authors.lastname: Mercer
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019446:Endotoxemia / Q000201:enzymology* / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D005753:Gastric Mucosa / Q000503:physiopathology; D007269:Injections, Intra-Arterial; D008070:Lipopolysaccharides / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017207:Rats, Sprague-Dawley; D026423:S-Nitroso-N-Acetylpenicillamine / Q000008:administration & dosage / Q000494:pharmacology; D013270:Stomach / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D013656:Taurocholic Acid / Q000494:pharmacology; D013997:Time Factors
chemical_list: D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D000431:Ethanol; D013656:Taurocholic Acid; D026423:S-Nitroso-N-Acetylpenicillamine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D019331:NG-Nitroarginine Methyl Ester