Mechanisms of Action of the Gasotransmitter Hydrogen Sulfide in Modulating Contractile Activity of Longitudinal Muscle of Rat Ileum

This study aims to determine mechanisms of action of the gasotransmitter hydrogen sulfide (H2S) on contractile activity in longitudinal muscle of rat ileum. Ileal longitudinal muscle strips were prepared to measure isometric contractions. Effects of sodium hydrosulfide (NaHS), a donor of H2S, were evaluated on spontaneous contractile activity and after enhanced contractile activity with bethanechol. l-cysteine was evaluated as a potential endogenous donor of H2S. We evaluated involvement of extrinsic nerves, enteric nervous system, visceral afferent nerves, nitric oxide, and K (ATP) (+) channel and K (Ca) (+) channel activity on the action of H2S using non-adrenergic/non-cholinergic conditions, tetrodotoxin, capsaicin, l-N-G-nitro arginine (l-NNA), glibenclamide, and apamin, respectively, as well as electrical field stimulation. NaHS dose-dependently and reversibly inhibited spontaneous and bethanechol-stimulated contractile activity (p < 0.05). l-cysteine had no inhibitory effect. Non-adrenergic/non-cholinergic conditions, tetrodotoxin, capsaicin, l-NNA, glibenclamide, or apamin had no major effect on total contractile activity by NaHS, although both tetrodotoxin and apamin decreased the frequency of bethanechol-enhanced contractile activity (p < 0.05). We could not demonstrate H2S release by electrical field stimulation but did show that inhibition of cystathionine beta synthase, an endogenous source of H2S, augmented the inhibitory effect of low-frequency electrical field stimulation. H2S inhibits contractile activity of ileal longitudinal muscle dose-dependently but not through pathways mediated by the extrinsic or enteric nervous system, visceral afferent nerves, nitric oxide, K (ATP) (+) channels, or K (Ca) (+) channels.