Differing effects of two nitric oxide synthase inhibitors on experimental colitis.
BACKGROUND/AIMS: The aim of this study was to investigate the effects of two inhibitors of nitric oxide synthase on a rat model of colitis. METHODOLOGY: Colitis was induced by administration of an enema containing trinitrobenzene sulfonic acid. This colitis was treated everyday for one week with NG-nitro-L-arginine (10 mg/kg, i.v.), which is a non-selective inhibitor of both constitutive nitric oxide synthase and inducible nitric oxide synthase, or aminoguanidine (10 mg/kg, i.v.) which is an inhibitor of inducible nitric oxide synthase. Exposure to the trinitrobenzene sulfonic acid enema inhibited the increase in body weight of rats, and markedly increased the colonic damage scores, wet weight, thiobarbituric acid-reactive substances and myeloperoxidase activity. RESULTS: The inhibition of weight increase caused by trinitrobenzene sulfonic acid was significantly reduced by aminoguanidine treatment, whereas weight loss tended to be aggravated by NG-nitro-L-arginine treatment. The increases in the colonic damage scores, wet weight, thiobarbituric acid-reactive substances and myeloperoxidase activity in trinitrobenzene sulfonic acid-colitis were significantly inhibited by aminoguanidine treatment, although they tended to be aggravated by NG-nitro-L-arginine treatment. CONCLUSIONS: These results suggest that an inhibitor of inducible nitric oxide synthase, but not of constitutive nitric oxide synthase, was effective in treating experimental colitis in rats.