Effects of hydrogen sulfide on relaxation responses in the lower esophageal sphincter in rabbits: the potential role of potassium channels

Naunyn Schmiedebergs Arch Pharmacol. 2024 Mar;397(3):1537-1550. doi: 10.1007/s00210-023-02695-z. Epub 2023 Sep 5.

Abstract

Hydrogen sulfide (H2S) is a significant physiologic inhibitory neurotransmitter. The main goal of this research was to examine the contribution of diverse potassium (K+) channels and nitric oxide (NO) in mediating the H2S effect on electrical field stimulation (EFS)-induced neurogenic contractile responses in the lower esophageal sphincter (LES). EFS-induced contractile responses of rabbit isolated LES strips were recorded using force transducers in organ baths that contain Krebs-Henseleit solutions (20 ml). Cumulative doses of NaHS, L-cysteine, PAG, and AOAA were evaluated in NO-dependent and NO-independent groups. The experiments were conducted again in the presence of K+ channel blockers. In both NO-dependent and NO-independent groups, NaHS, L-cysteine, PAG, and AOAA significantly reduced EFS-induced contractile responses. In the NO-dependent group, the effect of NaHS and L-cysteine decreased in the presence of 4-AP, and also the effect of NaHS decreased in the NO-dependent and independent group in the presence of TEA. In the NO-independent group, K+ channel blockers didn't change L-cysteine-induced relaxations. K+ channel blockers had no impact on the effects of PAG and AOAA. In addition, NaHS significantly relaxed 80-mM KCl-induced contractions, whereas L-cysteine, PAG, and AOAA did not. In the present study, H2S decreased the amplitudes of EFS-induced contraction responses. These results suggest that Kv channels and NO significantly contribute to exogenous H2S and endogenous H2S precursor L-cysteine inhibitory effect on lower esophageal sphincter smooth muscle.

Keywords: Hydrogen sulfide; L-cysteine; Lower esophageal sphincter; Nitric oxide; Potassium channels; Smooth muscle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cysteine / pharmacology
  • Esophageal Sphincter, Lower / metabolism
  • Hydrogen Sulfide* / metabolism
  • Hydrogen Sulfide* / pharmacology
  • Nitric Oxide / metabolism
  • Potassium Channels
  • Rabbits
  • Sulfides*

Substances

  • Hydrogen Sulfide
  • Potassium Channels
  • Cysteine
  • sodium bisulfide
  • Nitric Oxide
  • Sulfides