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Abstract

Effects of nitric oxide synthase inhibition on the pathophysiology observed in a model of chronic granulomatous colitis.

M B Grisham, R D Specian and T E Zimmerman
Journal of Pharmacology and Experimental Therapeutics November 1994, 271 (2) 1114-1121;
M B Grisham
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R D Specian
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T E Zimmerman
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Abstract

The objective of this study was to assess the role that nitric oxide (NO) may play in mediating the colonic inflammation observed in a model of chronic granulomatous colitis using two pharmacologically different inhibitors of nitric oxide synthase (NOS). The NOS inhibitors NG-nitro-L-arginine methyl ester (L-NAME; 15 mumol/kg/day) and aminoguanidine (AG; 15 mumol/kg/day) were administered to rats in their drinking water, beginning 3 days before the induction of colitis and continuing for the entire 3-week period. We found that chronic NOS inhibition by L-NAME or AG significantly attenuated the peptidoglycan/polysacchride (PG/PS)-induced increases in macroscopic colonic inflammation scores and colonic MPO activity. Only AG, and not L-NAME, attenuated the PG/PS-induced increases in colon dry weight. Both L-NAME and AG significantly attenuated the PG/PS-induced increases in spleen inflammation, whereas neither drug significantly attenuated the PG/PS-induced liver inflammation. Although both L-NAME and AG inhibited NO production in vivo, as measured by decreases in plasma nitrite and nitrate levels, only AG was found to attenuate these values significantly (38 +/- 3 vs. 83 +/- 8 microM, respectively; P < .05). Finally, administration of L-NAME, but not of AG, significantly increased mean arterial pressure from 83 mm Hg in colitic animals to 105 mm Hg in the PG/PS+L-NAME-treated animals (P < .05). We conclude that NO may play an important role in mediating some of the pathophysiology associated with this model of chronic granulomatous colitis.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 271, Issue 2
1 Nov 1994
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Abstract

Effects of nitric oxide synthase inhibition on the pathophysiology observed in a model of chronic granulomatous colitis.

M B Grisham, R D Specian and T E Zimmerman
Journal of Pharmacology and Experimental Therapeutics November 1, 1994, 271 (2) 1114-1121;

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Abstract

Effects of nitric oxide synthase inhibition on the pathophysiology observed in a model of chronic granulomatous colitis.

M B Grisham, R D Specian and T E Zimmerman
Journal of Pharmacology and Experimental Therapeutics November 1, 1994, 271 (2) 1114-1121;
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