NITRIC-OXIDE AND CHRONIC COLITIS

Nitric oxide (NO) is thought to play an important role in modulating t he inflammatory response by virtue of its ability to affect bloodflow, leukocyte function and cell viability. The objective of this study wa s to assess the role that NO may play in mediating the mucosal injury and inflammation in a model of chronic granulomatous colitis using two pharmacologically different inhibitors of nitric oxide synthase (NOS) . Chronic granulomatous colitis with liver and spleen inflammation was induced in female Lewis rats via the subserosal (intramural) injectio n of peptidoglycan/polysaccharide (PG/PS) derived from group A strepto cocci. Chronic NOS inhibition by oral administration of N-G-nitro-L-ar ginine methyl ester (L-NAME) (15 mu mol/kg/day) or amino-guanidine (AG ) (15 mu mol/kg/day) was found to attenuate the PG/PS-induced increase s in macroscopic colonic inflammation scores and colonic myeloperoxida se activity. Only AG - not L-NAME - attenuated the PG/PS-induced incre ases in colon dry weight. Both L-NAME and AG significantly attenuated the PG/PS-induced increases in spleen weight whereas neither was effec tive at significantly attenuating the PG/PS-induced increases in liver weight. Although both L-NAME and AG inhibited NO production in vivo, as measured by decreases in plasma nitrite and nitrate levels, only AG produced significantly lower values (38+/-3 versus 83+/-8 mu M, respe ctively, P<0.05). Finally, L-NAME, but not AG, administration signific antly increased mean arterial pressure from 83 mmHg in colitic animals to 105 mmHg in the PG/PS+ L-NAME-treated animals (P<0.05). It is conc luded that NO may play an important role in mediating some of the path ophysiology associated with this model of chronic granulomatous coliti s.