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

Abstract

Both nitric oxide synthase (NOS) and cyclooxygenase (COX) have inducible isoforms that are up-regulated during inflammatory states. However, the interaction between these enzymes is not clearly understood. The objective was to clarify the interactions between NOS and COX in the rat gastric mucosa in the presence and absence of lipopolysaccharide. Laboratory study. Medical school laboratory. Female Sprague-Dawley rats. We used nonselective and selective COX inhibitors to determine the role of COX on inducible NOS (iNOS) expression in the gastric mucosa. The nonselective COX inhibitors salicylate and indomethacin enhanced the expression of iNOS in the rat gastric mucosa and exacerbated gastric injury in the presence of lipopolysaccharide, effects reversed by exogenous prostaglandin E2. Selective COX-1 inhibition with SC560 similarly increased gastric iNOS expression and exacerbated gastric injury, while the selective COX-2 inhibitor NS398 had no effect on iNOS expression or gastric injury in the presence of lipopolysaccharide. These data suggest that COX-1 derived prostaglandins exert an inhibitory effect on gastric iNOS during endotoxemia, and this may represent a potential cytoprotective mechanism not previously recognized for this enzyme, since up-regulation of iNOS is deleterious in some tissues.