No abstract

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 examined in 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 omega-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 by L-arginine, but not D-arginine. The results indicate that nitric oxide is an important mediator for nonadrenergic, noncholinergic nerve effects in the human esophagus and lower esophageal sphincter.

The present study was performed to establish the intrinsic frequency of the slow waves in different regions of the cat stomach, to define the propagation velocity of the slow wave along the stomach, and to determine whether endogenous prostaglandins can affect the slow wave frequency. In 20 cats, electrical activity was recorded from the anterior wall of the intact stomach in vivo and in vitro, and in vitro after cutting the stomach into 16 pieces to isolate each pair of electrodes. In vivo, slow waves (4.1 +/- 0.5 cpm) were seen only from mid corpus to pylorus, the apparent propagation velocity decreasing towards the antrum. In vitro: (a) after cutting, the slow wave frequency increased, to a maximum in 1 h (12 +/- 1.8 cpm; range 10.2-17.3), with the highest frequency always in the mid or orad corpus, usually on the greater curvature (GC), (b) with indomethacin (10(-5) M) the increase in slow wave frequency was prevented or reversed, and there was a frequency gradient with the highest frequency (4.4 +/- 1.2 cpm) uniformly located in the most proximal active site on the GC, and (c) slow waves on the GC were more stable, regular and continuous than on the lesser curvature (LC), the difference being most evident in the corpus. The results suggest that the cat stomach behaves as a system of electrically coupled oscillators of different frequencies. The dominant oscillator of highest frequency is situated in the proximal corpus of the GC, with the remainder of the distal stomach entrained at this frequency. All gastric slow wave oscillators can be driven to higher frequencies by endogenous prostaglandins. The decreasing velocity of slow wave propagation distally suggests that oscillator properties and/or coupling among oscillators differs in the cat.