Role of nitric oxide in inflammation-induced suppression of secretion in amouse model of acute colitis

The role of nitric oxide (NO) derived from the inducible isoform of NO synt hase (iNOS) in epithelial transport dysfunction was studied in a model of c olitis induced in mice by intrarectal 2,4,6-trinitrobenzenesulfonic acid in 30% ethanol. Expression of iNOS mRNA was determined by RT-PCR. Electrolyte transport studies were conducted in Ussing chambers in which segments of i n flamed colon were incubated with or without the selective iNOS inhibitor L-N-6-(1-iminoethyl)lysine (L-NIL). Seven days after the induction of colit is, colonic tissue exhibited increased myeloperoxidase activity compared wi th saline controls. There was a detectable basal expression of iNOS mRNA, b ut expression was increased 3.7-fold in inflamed colons. Inflammation also caused an increase in iNOS activity and a concomitant decrease in constitut ive NOS activity. In Ussing chamber experiments, there was a decreased resp onse to electrical field stimulation in inflamed tissue, which was partiall y reversed by pretreatment of the tissue with L-NIL. The short-circuit curr ent response to the muscarinic agonist carbachol was also reduced in inflam mation, but this was not reversed by L-NIL. In summary NO derived from iNOS mediates, in part, inflammation-induced suppression of neurally evoked ele ctrolyte transport.