Investigation of the mechanism of the relaxing effect of hydrogen sulfide on electrical field stimulation-mediated neurogenic contractile responses in the isolated rabbit lower esophageal sphincter

H2S is a significant physiological inhibitory neurotransmitter in the gastrointestinal tract. Recent studies have shown that H2S can be synthesised endogenously in different tissues and interacts with NO in many tissues. The aim of this study was to investigate the contribution of various K+ channels and NO to the H2S effect on EFS-induced neurogenic contractile responses of the LES. EFS-induced contractile responses of rabbit isolated LES strips were recorded using force transducers in organ baths containing Krebs-Henseleit solutions. The effects ofcumulative doses of NaHS (H2S releaser, 10-6-3x10-3M), L-Cysteine (H2S precursor, 10-5-3x10-3M), PAG and AOAA (H2S synthesis enzyme inhibitors, 10-5-3x10-3 M) on EFS-mediated contraction responses in NO-dependent and NO-independent (in the presence of L-NAME) groups were evaluated. The effects of each group were re-evaluated in the presence of Glibenclamide (KATP channel blocker), TEA (non-selective K channel blocker), 4-AP (KV channel blocker) and Iberiotoxin (KCa channel blocker). In both NO-dependent and NO-independent groups, NaHS, L-Cysteine, PAG and AOAA significantly reduced EFS-mediated contractile responses. In the NO-dependent group, the effect of NaHS and L-Cysteine was reduced in the presence of 4-AP, also the effect of NaHS was reduced in the presence of TEA in the NO-dependent and independent group. In the NO-independent group, K+ channel blockers did not change L-Cysteine-induced relaxations. K+ channel blockers had no effect on the effects of PAG and AOAA. Furthermore, NaHS significantly relaxed 80-mM KCl-induced contractions, whereas L-Cysteine, PAG and AOAA did not. In this study, H2S reduced the amplitudes of EFS-induced contraction responses.These results suggest that KV channels and NO significantly contribute to the inhibitory effect of exogenous H2S and endogenous H2S precursor L-Cysteine on lower oesophageal sphincter smooth muscle. Keywords: Hydrogen sulphide, l-cysteine, potassium channels, nitric oxide, lower esophageal sphincter, electrical field stimulation