Vasoconstriction triggered by hydrogen sulfide: Evidence for Na,K,2Clcotransport and L-type Ca channel-mediated pathway.

Objectives: This study examined the dose-dependent actions of hydrogen sulfide donor sodium hydrosulphide (NaHS) on isometric contractions and ion transport in rat aorta smooth muscle cells (SMC).

Methods: Isometric contraction was measured in ring aortas segments from male Wistar rats. Activity of Na/K-pump and Na,K,2Clcotransport was measured in cultured endothelial and smooth muscle cells from the rat aorta as ouabain-sensitive and ouabain-resistant, bumetanide-sensitive components of the Rb influx, respectively.

Results: NaHS exhibited the bimodal action on contractions triggered by modest depolarization ([K]=30 mM). At 10 M, NaHS augmented contractions of intact and endothelium-denuded strips by ~ 15% and 25%, respectively, whereas at concentration of 10 M it decreased contractile responses by more than two-fold. Contractions evoked by 10 M NaHS were completely abolished by bumetanide, a potent inhibitor of Na,K,2Clcotransport, whereas the inhibition seen at 10 M NaHS was suppressed in the presence of K channel blocker TEA. In cultured SMC, 5×10 M NaHS increased Na,K,2Cl - cotransport without any effect on the activity of this carrier in endothelial cells. In depolarized SMC, Ca influx was enhanced in the presence of 10 M NaHS and suppressed under elevation of [NaHS] up to 10 M. Ca influx triggered by 10 M NaHS was abolished by bumetanide and L-type Ca channel blocker nicardipine.

Conclusions: Our results strongly suggest that contractions of rat aortic rings triggered by low doses of NaHS are mediated by activation of Na,K,2Clcotransport and Ca influx via L-type channels.