Nitric oxide mediates inhibitory nerve effects in human esophagus and lower esophageal sphincter

The effect of inhibition of nitric oxide synthase on nonadrenergic, noncholinergic nerve-mediated responses in circular smooth muscle of the human esophageal body and lower esophageal sphincter (LES) was examinedin vitro. Tissues were obtained from 10 patients (eight esophageal resection for cancer, two transplant donors). Muscle strips from the LES developed significant spontaneous tension (11.6 ± 2.1 mN/mm²,N=6) and relaxed in response to electrical stimulation. The nitric oxide synthase inhibitor,N -nitro-l-arginine (NNA), at 10^–5 M, inhibited the relaxation, but had no significant effect on the spontaneous tension (13.0 ± 2.6 mN/mm²,P=0.07). Esophageal body strips developed little spontaneous tension, demonstrated an off contraction following the cessation of the electrical stimulus, and when contracted with 10^–5 M carbachol, relaxed during electrical stimulation. NNA (10^–5 M) inhibited the off contraction and the relaxation seen after carbachol and unmasked a prominent intrastimulus contraction. This intrastimulus contraction was enhanced by eserine and inhibited by atropine and tetrodotoxin. NNA showed similar potency in the esophageal body and LES and its effects were reversed byl-arginine, but notd-arginine. The results indicate that nitric oxide is an important mediator for nonadrenergic, noncholinergic nerve effects in the human esophagus and lower esophageal sphincter.This research was supported in part by an ICI Pharma/Medical Research Council of Canada Research Fellowship grant awarded to H.G. Preiksaitis and a Medical Research Council Program Grant PG8.