Dual role of endogenous nitric oxide in development of dextran sulfate sodium-induced colitis in rats

G. Rumi, R. Tsubouchi, H. Nishio, S. Kato, G. Mózsik, Koji Takeuchi

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The role of nitric oxide (NO) in the etiology of ulcerative colitis is controversial with reports of the improvement and aggravation of colonic lesions by inducible NO synthase (iNOS) inhibitors. In the present study, we compared the effect of the selective iNOS inhibitor aminoguanidine and the nonselective NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME) on a dextran sulfate sodium (DSS)-induced model of colitis in rats. Experimental colitis was induced by a 3% DSS-solution added to drinking water for 7 days. Aminoguanidine (5-20 mg/kg) and L-NAME (10 mg/kg) were administered p.o. twice daily for the first 3 days, the last 3 days or all 6 days of DSS treatment. Body weight and severity of colitis (diarrhea, bloody feces) were observed over a period of 7 days. DSS treatment resulted in severe colonic lesions, accompanied by diarrhea, bloody feces, decrease of body weight and colon shortening. All of the parameters investigated improved significantly with aminoguanidine treatment at 20 mg/kg for 6 days or the last 3 days of DSS-treatment, but L-NAME did not significantly affect the colitis during these periods. When L-NAME or aminoguanidine was given in the first 3 days of DSS treatment, the colonic lesions were slightly aggravated by L-NAME but not affected by aminoguanidine. The expression of iNOS mRNA was observed from the 3rd day of DSS treatment. These results suggested that endogenous NO exerts a biphasic influence on DSS-induced colitis, depending on the NOS isoenzyme; a beneficial effect of NO derived from constitutive NOS and a detrimental effect of NO produced by iNOS in the development of colitis.

Original languageEnglish
Pages (from-to)823-836
Number of pages14
JournalJournal of Physiology and Pharmacology
Volume55
Issue number4
Publication statusPublished - Dec 2004

Fingerprint

Dextran Sulfate
Colitis
NG-Nitroarginine Methyl Ester
Nitric Oxide
Nitric Oxide Synthase
Feces
Diarrhea
Body Weight
Nitric Oxide Synthase Type II
Ulcerative Colitis
Drinking Water
Isoenzymes
Colon
pimagedine
Messenger RNA

Keywords

  • Aminoguanidine
  • Experimental colitis
  • L-NAME
  • Nitric oxide
  • Rat

ASJC Scopus subject areas

  • Pharmacology
  • Physiology

Cite this

Dual role of endogenous nitric oxide in development of dextran sulfate sodium-induced colitis in rats. / Rumi, G.; Tsubouchi, R.; Nishio, H.; Kato, S.; Mózsik, G.; Takeuchi, Koji.

In: Journal of Physiology and Pharmacology, Vol. 55, No. 4, 12.2004, p. 823-836.

Research output: Contribution to journalArticle

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