Role of nitric oxide in the internal anal sphincter of Hirschsprung's disease.
It is not clear what contribution the internal anal sphincter (IAS) makes to the impaired motility observed in patients with Hirschsprung's disease (HD). Nitric oxide (NO) has recently been shown to be a neurotransmitter in the nonadrenergic noncholinergic (NANC) inhibitory nerves in the human gut. To clarify the physiologic significance of NO in the IAS of HD (aganglionosis), we investigated the enteric nerve responses on lesional (aganglionic) and normal IAS muscle strips above the dentate line. Lesional and normal IAS muscle strips above the dentate line were derived from patients with HD (10 cases) and patients who underwent rectal amputation for low rectal cancer (12 cases). A mechanographic technique was used to evaluate in vitro muscle responses to electrical field stimulation (EFS) before and after treatment with various autonomic nerve blockers, N(G)-L-nitroarginine, and L-arginine. The following results were obtained: (1) Cholinergic nerves are mainly involved in the regulation of enteric nerve responses to EFS in the normal IAS. (2) The aganglionic IAS of patients with HD was more strongly innervated by cholinergic nerves than the normal IAS (p < 0.05). (3) NANC inhibitory nerves were found to act on the normal IAS but had no effect on the enteric nerves in patients with aganglionosis. (4) NO was found to act on normal IAS, but no effect was observed in the aganglionic IAS. These findings suggest that innervation of the cholinergic nerves and a loss of NO mediation of NANC inhibitory nerves play an important role in the impaired motility observed in the IAS with HD.
Tomita
Ryouichi
R
Department of Surgery, Nippon Dental University School of Dentistry at Tokyo, 2-3-16 Fujimi Chiyoda-ku, Tokyo 102-8158, Japan. rtomita-ndus@mvg.biglobe.ne.jp
Fujisaki
Shigeru
S
Tanjoh
Katsuhisa
K
Fukuzawa
Masahiro
M
D001003:Anal Canal / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D001120:Arginine / Q000494:pharmacology; D001707:Biopsy, Needle; D016022:Case-Control Studies; D002675:Child, Preschool; D046508:Culture Techniques; D004558:Electric Stimulation; D005260:Female; D005725:Ganglia, Autonomic / Q000187:drug effects*; D006627:Hirschsprung Disease / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D007223:Infant; D008297:Male; D009119:Muscle Contraction; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019335:Nitroarginine / Q000494:pharmacology; D011336:Probability; D012016:Reference Values; D012680:Sensitivity and Specificity
D018377:Neurotransmitter Agents; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine