Endogenous nitric oxide in the control of esophageal motility in humans

Recent animal studies have suggested that nitric oxide (NO) plays an important role in the regulation of esophageal motility, being partly responsible for latency period and latency gradient between the onset of a swallow and contractions of esophageal circular smooth muscles. The aim of this study was to evaluate whether endogenous NO is responsible for physiological timing of forthcoming contractions in the human esophageal body after swallowing. Eight male volunteers (age 21-25 years, weight 67-82 kg) were involved in this placebo controlled study on the effects of increasing doses of the NO synthase blocker, NG-monomethyl-L-arginine (L-NMMA 1.0-4.0 mumol/min i.v.), and/or L-arginine (L-arg) (30 mumol/kg-min i.v.) on the peristalsis of esophageal body in response to wet swallows (5 ml of water) and lower esophageal sphincter (LES) resting pressure. The esophageal motor activity was determined manometrically using 3-channel electronic catheter. Additionally, during all examinations arterial blood pressure (BP) was measured every 5 min. L-NMMA resulted in a significant and dose-dependent reduction in the latency period between swallows and the onset of contractions which was most pronounced in the distal esophagus (control: 7.07 +/- 0.74 s vs. L-NMMA 4.0 mumol/min: 5.87 +/- 0.57 s), and this effect was partially reversed after addition of L-arg to the L-NMMA infusion (6.91 +/- 0.62 s). L-NMMA infusion significantly reduced the duration of contractions and increased the velocity of onset propagation but did not change the amplitude of contractions and again, these effects were reversed during simultaneous infusion of L-arg. The resting tone of LES increased significantly during infusion of L-NMMA and these effects were reversed by addition of L-arg. The mean BP significantly increased during infusion of L-NMMA (control 97.0 +/- 5.7 vs. L-NMMA 4.0 mumol/min: 116.4 +/- 3.1 mm Hg) and this was also reversed by L-arg. We conclude that in humans endogenous NO is involved, at least in part, in the physiological regulation of motility patterns of the distal esophageal body and LES.