Vasomotor effects of hydrogen sulfide in human umbilical vessels

Hydrogen sulfide (H₂S) has recently emerged as a biologically active gas with multiple effects on the cardiovascular system. We aimed to investigate the vasomotor actions of sodium sulfide (Na₂S), which forms H₂S and HS^- in solution, in human umbilical artery (HUA) and vein (HUV) rings. In addition, we examined by immunocytochemistry the expression and localization of cystathionine β-synthase (CBS), cystathionine lyase (CSE), and 3-mercaptopyruvate sulphurtransferase (MPST), the enzymes responsible for endogenous H₂S production. Human umbilical vessels were compared with chicken embryo umbilical vessels. HUA and HUV expressed a robust signal for CSE, CBS, and 3-MPST in both endothelial and smooth muscle cells. However, HUA rings did not respond to Na₂S (10^-6M-10^-3M) either at resting tone or during contraction evoked by serotonin or KCl. Similarly, the extraembryonic part of chicken allantoic artery did not respond to Na₂S. In contrast, Na₂S induced a concentration-dependent contraction in HUV rings under resting tone and a concentration-dependent relaxation when the H₂UV rings were contracted with serotonin (42 ± 5% relaxation) or KCl (12 ± 5% relaxation). Na₂S-induced contraction of HUV was impaired following removal of extracellular Ca²⁺, endothelial denudation, NO synthase inhibition (L-NAME), or soluble guanylate cyclase (sGC) inhibition (ODQ). Na₂S-induced relaxation of HUV was impaired by the K_ATP channel inhibitor glibenclamide. In conclusion, H₂S does not have vasomotor effects on HUA but induced contraction (mediated through inactivation of the NO/sGC axis) and relaxation (mediated through K_ATP channels) in HUV. Our data suggest a role for H₂S in the venous side of human umbilical circulation.