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Cyclooxygenase-1 suppresses lipopolysaccharide-induced changes in rat gastric inducible nitric oxide synthase

Sonlee D West1, James W Suliburk, Kenneth S Helmer

  • 1Department of Surgery at the University of New Mexico Health Sciences Center, Albuquerque, NM, USA.

Critical Care Medicine
|January 25, 2008
PubMed
Abstract

Insights

Cyclooxygenase-1 (COX-1) derived prostaglandins inhibit inducible nitric oxide synthase (iNOS) in the rat gastric mucosa during inflammation. This interaction may offer cytoprotection against endotoxemia-induced gastric injury.

Area of Science:

  • Gastroenterology
  • Inflammation Research
  • Enzyme Interactions

Background:

  • Inducible isoforms of nitric oxide synthase (NOS) and cyclooxygenase (COX) are upregulated during inflammation.
  • The precise interaction between NOS and COX in inflammatory states, particularly within the gastric mucosa, remains incompletely understood.

Purpose of the Study:

  • To elucidate the interactions between NOS and COX pathways in the rat gastric mucosa.
  • To investigate the role of COX in regulating inducible NOS (iNOS) expression under inflammatory conditions induced by lipopolysaccharide.

Main Methods:

  • A laboratory study utilizing female Sprague-Dawley rats.
  • Employing nonselective and selective COX inhibitors (salicylate, indomethacin, SC560, NS398) to assess their impact on iNOS expression and gastric injury.
  • Lipopolysaccharide was used to induce an inflammatory state.

Main Results:

  • Nonselective COX inhibition (salicylate, indomethacin) and selective COX-1 inhibition (SC560) enhanced iNOS expression and exacerbated gastric injury in lipopolysaccharide-treated rats.
  • These effects were reversed by exogenous prostaglandin E2.
  • Selective COX-2 inhibition (NS398) did not affect iNOS expression or gastric injury.

Conclusions:

  • COX-1 derived prostaglandins exert an inhibitory influence on gastric iNOS during endotoxemia.
  • This interaction suggests a potential cytoprotective mechanism involving COX-1, particularly in mitigating the deleterious effects of iNOS upregulation in the gastric mucosa.

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