POTENTIAL ROLE OF NITRIC-OXIDE IN A MODEL OF CHRONIC COLITIS IN RHESUS MACAQUES

Background/Aims: Excess nitric oxide formation, via the inducible NO s ynthase isoform, has been implicated in the pathogenesis of experiment al and clinical inflammatory bowel disease. The aim of this study was to assess the site, enzyme source, and magnitude of NO production in j uvenile rhesus macaques with idiopathic colitis. Methods: NO productio n was assessed systemically from plasma and urine levels of reactive n itrogen intermediates and locally by the formation of [H-3]citrulline from [H-3]arginine and reduced nicotinamide adenine dinucleotide phosp hate (NADPH) diaphorase histochemistry. Inducible NO synthase gene exp ression was assessed by reverse-transcription polymerase chain reactio n. Results: Plasma and urine levels of reactive nitrogen intermediates were greater in colitic animals than in control monkeys by 13- and 5- fold, respectively. NADPH diaphorase activity in normal animals was co nfined to the myenteric plexus. In colitis, staining was also apparent in crypt abscesses and superficial epithelial and mucosal bands. Gene expression for inducible NO synthase was only found in colitic specim ens. Colonic [H-3]citrulline formation was markedly elevated in coliti c specimens, and the inducible isoform accounted for 58% of total acti vity. Conclusions: It is proposed that excess NO, formed via the induc ible form of NO synthase, contributes to the mucosal inflammation and symptoms of this idiopathic colitis model.