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.