Role of nitric oxide in lower esophageal sphincter relaxation to swallowing

Life Sci. 1992;50(17):1263-72. doi: 10.1016/0024-3205(92)90326-k.

Abstract

Studies were performed in the opossum to define the role of the L-arginine-nitric oxide (NO) pathway in lower esophageal sphincter (LES) relaxation to swallowing and vagal stimulation in viv and intramural nerve stimulation in vitro. In vivo, L-NAME, a water soluble NO synthase (NOS) inhibitor, caused antagonism of LES relaxation due to reflex-induced swallowing. L-NAME (20 mg/kg i.v.) reduced the amplitude of swallow induced relaxation from 88% to 28%. LES relaxation due to electrical stimulation of peripheral end of decentralized vagus nerve was also antagonized. The effects of L-NAME were reversed by L-arginine, but not by D-arginine. L-NAME treatment did not antagonize LES relaxation to intravenous administration of isoproterenol. In vitro, NO and sodium nitroprusside (SNP) caused a decrease in the sphincter tone. The relaxing effect caused by NO and SNP was not antagonized by tetrodotoxin or omega-conotoxin. Inhibitors of NO synthase, L-NMMA and L-NNA, caused slight increase in the spontaneous resting LES tone and concentration-dependent antagonism of electrical field stimulation (EFS) induced LES relaxation. L-NNA (10(-4)M) abolished EFS induced LES relaxation at low frequencies (less than 5 Hz) and antagonized the relaxation to a value 20% of the control at 20 Hz. The antagonistic action of L-NMMA and L-NNA was unaffected by D-arginine but was reversed by L-arginine. The inhibitory effect of NO, SNP, or two other putative inhibitory neurotransmitters (VIP and CGRP) on the LES was not antagonized by L-NNA. These studies show that inhibitors of NO synthase selectively antagonize LES relaxation to all three modes of intramural inhibitory nerve stimulation including physiological swallowing. These studies suggest that the L-arginine-nitric oxide pathway is involved in physiological relaxation of the LES.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Oxidoreductases / antagonists & inhibitors
  • Animals
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Deglutition*
  • Electric Stimulation
  • Electrophysiology
  • Esophagogastric Junction / drug effects
  • Esophagogastric Junction / physiology*
  • Female
  • Male
  • Muscle Relaxation / drug effects
  • Muscle Relaxation / physiology*
  • NG-Nitroarginine Methyl Ester
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase
  • Nitroarginine
  • Opossums
  • Vagus Nerve / physiology

Substances

  • Nitroarginine
  • Nitric Oxide
  • Arginine
  • Nitric Oxide Synthase
  • Amino Acid Oxidoreductases
  • NG-Nitroarginine Methyl Ester