Physiological studies on nitric oxide in the lower esophageal sphincter of patients with reflux esophagitis

Nitric oxide has recently been shown to be a neurotransmitter in the non-adrenergic non-cholinergic inhibitory nerves in the digestive tract. To clarify the significance of nitric oxide in the lower esophageal sphincter of patients with reflux esophagitis, we have investigated enteric nerve responses in lower esophageal sphincter specimens obtained from the patients with gastric cancer who had reflux esophagitis, using the normal lower esophageal sphincter as a control.

Lower esophageal sphincter specimens were obtained from 6 patients who had gastric cancer with reflux esophagitis, and normal lower esophageal sphincter specimens were obtained from 12 patients who had gastric cancer without gastroesophageal reflux disease. A mechanograph was used to evaluate in vitro lower esophageal sphincter muscle responses to electrical field stimulation of the adrenergic and cholinergic nerves before and after treatment with various autonomic nerve blockers, and NG-nitro-L-arginine and L-arginine.

1) Cholinergic nerves were more dominant in the normal lower esophageal sphincter than in the lower esophageal sphincter with reflux esophagitis (p < 0.01); 2) non-adrenergic non-cholinergic inhibitory nerves were significantly found to act more on the lower esophageal sphincter with reflux esophagitis than those in the normal lower esophageal sphincter (p < 0.01); 3) nitric oxide mediates the relaxation reaction via non-adrenergic non-cholinergic inhibitory nerves in the normal lower esophageal sphincter and the lower esophageal sphincter with reflux esophagitis; 4) The relaxation reaction of nitric oxide was observed in the normal lower esophageal sphincter and increased in the lower esophageal sphincter with reflux esophagitis.

These findings suggest that the cholinergic and non-adrenergic non-cholinergic inhibitory nerves play important roles in regulating contraction and relaxation of the human lower esophageal sphincter, and nitric oxide plays an important role in non-adrenergic non-cholinergic inhibitory nerves of the human lower esophageal sphincter. In addition, a decrease of the action of cholinergic nerves and an increase of the action of non-adrenergic non-cholinergic inhibitory nerves by nitric oxide may be largely related to the low lower esophageal sphincter pressure observed in the patients with reflux esophagitis.