ROLE OF NITRIC-OXIDE IN THE COLON OF PATIENTS WITH ULCERATIVE-COLITIS

The cause of impaired motility, such as diarrhea and toxic megacolon, in patients with ulcerative colitis (UC) is unknown. Nitric oxide (NO) has been shown to be a neurotransmitter in the nonadrenergic noncholi nergic (NANC) inhibitory nerves in the human gut. To assess the physio logic significance of NO in the colon of patients with UC, we investig ated enteric nerve responses on lesional and normal bowel segments der ived from patients with ulcerative colitis (n = 6) and patients who un derwent colon resection for colonic cancers (n = 10). A mechanographic technique was used to evaluate in vitro muscle responses to electrica l field stimulation (EFS) of adrenergic and cholinergic nerves before and after treatment with various autonomic nerve blockers, including N -G-nitro-L-arginine (L-NNA) and L-arginine. The results showed that (1 ) NANC inhibitory nerves were found to act on both normal colon and UC colon; (2) the colon with UC was more strongly innervated by NANC inh ibitory nerves than the normal colon; (3) L-NNA concentration-dependen tly inhibited the relaxation in response to EFS in the colon of both n ormal and UC colon; and (4) this inhibitory effect in the colon of bot h normal and UC patients was reversed by L-arginine; (5) NO acts more strongly in the UC colon than the normal colon, These findings suggest that NANC inhibitory nerves play an important role in the impaired mo tility observed in patients with UC and that NO plays an important rol e as a neurotransmitter in NANC inhibitory nerves of human colon.