Oral administration of inducible nitric oxide synthase inhibitors reduces nitric oxide synthesis but has no effect on the severity of experimental colitis

Background: Increased concentrations of nitrate and nitrite (the breakdown products of nitric oxide) in the serum and faeces of patients with inflamma tory bowel disease (IBD) suggests that increased synthesis of nitric oxide occurs in IBD. The aim of this study was to assess aminoguanidine (AMG), a selective inhibitor of inducible nitric oxide synthase, with regard to its effectiveness as a nitric oxide inhibitor and as a modulator of inflammatio n in trinitrobenzene sulfonic acid (TNBS)-induced colitis. Materials and Me thods: Colitis was induced in Wistar rats. Selective (AMG) and non-selectiv e (1-nitroso-arginine methyl ester (1-NAME)) inhibitors of nitric oxide syn thase were given in the drinking water. Colonic citrulline and arginine con centrations were assessed using high-performance liquid chromatography. The severity of colitis was assessed by a macroscopic scoring system. Results: Both 1-NAME and AMG successfully reduced nitric oxide synthesis. There was no evidence of substrate depletion in the colonic wall. Neither of the age nts reduced the severity of colonic inflammation. Conclusions: Oral adminis tration of nitric oxide synthase inhibitors reduced nitric oxide synthesis in the colonic wall. This study does not provide evidence to support a role for nitric oxide in the pathogenesis of colonic inflammation in TNBS colit is.