The role of nitric oxide (NO) in the human internal anal sphincter

Nitric oxide (NO) has recently been shown to be a neurotransmitter in nonadrenergic noncholinergic (NANC) inhibitory nerves in the human gut. To clarify the physiological significance of NO in the human internal anal sphincter (IAS), we investigated enteric nervous responses in normal IAS muscle strips above the dentate line, obtained from patients with rectal cancer. Methods. Normal IAS muscle strips above the dentate line, obtained from ten patients who underwent rectal amputation for low rectal cancers were used. The subjects consisted of eight men and two women, aged from 46–72 years (mean age, 54.2 years). A mechanographic technique was used to evaluate in-vitro IAS muscle responses to electrical field stimulation (EFS) of adrenergic and cholinergic nerves before and after treatment with various autonomic nerve blockers, NG-nitro-l-arginine (l-NNA) and l-arginine. Results. Excitatory nerves were mainly involved in the regulation of enteric nerve responses to EFS in the baseline condition of the study, and NANC inhibitory nerves acted on the normal IAS. l-NNA concentration-dependently inhibited the relaxation in response to EFS in the human IAS, and this inhibitory effect in the IAS was reversed by l-arginine. Conclusions. These findings suggest that NANC inhibitory nerves play important roles in regulating relaxation of the human IAS, and that NO plays an important role as a neurotransmitter in NANC inhibitory nerves of the human IAS.