Mechanisms underlying the vasorelaxant effect of hydrogen sulfide on human saphenous vein

Hydrogen sulfide (H₂ S) represents the third and the youngest member of the gaseous transmitters family. The dominant effect of H₂ S on isolated vessels is vasodilation. As the mechanism of H₂ S-induced relaxation in human vessels remains unclear, the present study aimed to investigate the effects of H₂ S donor, sodium hydrosulfide (NaHS), on isolated human saphenous vein (HSV) and to determine the mechanism of action. Our results showed that NaHS (1 µM-3 mM) induced a concentration-dependent relaxation of endothelium-intact HSV rings pre-contracted by phenylephrine. Pre-treatment with L-NAME, ODQ and KT5823 significantly inhibited NaHS-induced relaxation, while indomethacin induced partial inhibition. Among K⁺ channel blockers, the combination of apamin and TRAM-34 significantly affected the relaxation produced by NaHS, while iberiotoxin and glibenclamide only reduced maximal relaxation of HSV. NaHS partially relaxed endothelium-intact rings pre-contracted by high K⁺ , as well as phenylephrine-contracted rings in the presence of nifedipine. Additionally, the incubation of HSV rings with NaHS increased NO production. These results demonstrate that NaHS produces the concentration- and endothelium-dependent relaxation of isolated HSV. Vasorelaxation to NaHS probably involves activation of NO/cGMP/PKG pathway and partially prostacyclin. In addition, different K⁺ channels subtypes, especially SK_Ca and IK_Ca , as well as BK_Ca and K_ATP channels in high concentrations of NaHS, probably participate in the NaHS-induced vasorelaxation.