A role of nitric oxide in Hirschsprung's disease

Nitric oxide (NO) has recently been shown to be a neurotransmitter in the nonadrenergic noncholinergic (NANC) inhibitory nerves in the gastrointestinal tract. To clarify the significance of NO in Hirschsprung's disease (HD), enteric nerve responses in colonic tissue obtained from HD patients were investigated. Colonic tissue specimens were obtained from four patients with HD and from 11 patients without constipation who were used as controls. A mechanograph was used to evaluate in vitro colonic responses to electrical field stimulation (EFS) of the adrenergic and cholinergic nerves before and after treatment with various autonomic nerve blockers, and NG-nitro-L-arginine (L-NNA) and L-arginine with the following results: (1) NANC inhibitory nerves were found to act on normal human colon, but had no effect on aganglionic colon; (2) L-NNA concentration dependently inhibited the relaxation in response to EFS in the normal colon, but had no effect on aganglionic colon; and (3) this inhibitory effect was reversed by L-arginine in the normal colon, but had no effect on the aganglionic colon. Nitric oxide mediates the relaxation reaction of NANC inhibitory nerves in the human colon, but the effect of NO was absent in aganglionic colon. The loss of action by NO may be implicated in the impaired motility observed in aganglionic colon.