Differing effects of two nitric oxide synthase inhibitors on experimental colitis

Background/Aims: The aim of this study was to investigate the effects of tw o inhibitors of nitric oxide synthase on a rat model of colitis. Methodology: Colitis was induced by administration of an enema containing t rinitrobenzene sulfonic acid. This colitis was treated everyday for one wee k with Nc-nitro-L-arginine (10mg/kg, i.v.), which is a non-selective inhibi tor of both constitutive nitric oxide synthase and inducible nitric oxide s ynthase, or aminoguanidine (10mg/kg, i.v.) which is an inhibitor of inducib le nitric oxide synthase. Exposure to the trinitrobenzene sulfonic acid ene ma inhibited the increase in body weight of rats, and markedly increased th e colonic damage scores, wet weight, thiobarbituric acid-reactive substance s and myeloperoxidase activity. Results: The inhibition of weight increase caused by trinitrobenzene sulfon ic acid was significantly reduced by aminoguanidine treatment, whereas weig ht loss tended to be aggravated by N-G-nitro-(L)-arginine treatment. The in creases in the colonic damage scores, wet weight, thiobarbituric acid-react ive substances and myeloperoxidase activity in trinitrobenzene sulfonic aci d-colitis were significantly inhibited by aminoguanidine treatment, althoug h they tended to be aggravated by N-G-nitro-L-arginine treatment. Conclusions: These results suggest that an inhibitor of inducible nitric ox ide synthase, but not of constitutive nitric oxide synthase, was effective in treating experimental colitis in rats.