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 noncholinergic (NANC) inhibitory nerves in the human gut. To assess the physiologic significance of NO in the colon of patients with UC, we investigated enteric nerve responses on lesional and normal bowel segments derived from patients with ulcerative colitis (n = 6) and patients who underwent colon resection for colonic cancers (n = 10). A mechanographic technique was used to evaluate in vitro muscle responses to electrical field stimulation (EFS) of adrenergic and cholinergic nerves before and after treatment with various autonomic nerve blockers, including NG-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 inhibitory nerves than the normal colon; (3) L-NNA concentration-dependently inhibited the relaxation in response to EFS in the colon of both normal and UC colon; and (4) this inhibitory effect in the colon of both 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 motility observed in patients with UC and that NO plays an important role as a neurotransmitter in NANC inhibitory nerves of human colon.