Differing effects of two nitric oxide synthase inhibitors on experimental colitis.
OBJECTIVE
The aim of this study was to investigate the effects of two inhibitors of nitric oxide synthase on a rat model of colitis.


METHODS
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.
Department of Gastroenterology, Takeda Hospital, Kyoto, Japan.
T
T
Yamaguchi
N
N
Yoshida
E
E
Ichiishi
N
N
Sugimoto
Y
Y
Naito
T
T
Yoshikawa
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II; D019335:Nitroarginine / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014302:Trinitrobenzenesulfonic Acid
D004791:Enzyme Inhibitors; D006146:Guanidines; D017392:Thiobarbituric Acid Reactive Substances; D019335:Nitroarginine; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C004479:pimagedine