Vasodilator activity of hydrogen sulfide (H₂S) in human mesenteric arteries

The role of endogenous H₂S has been highlighted as a gaseous transmitter. The vascular smooth muscle inhibitory effects of H₂S have been characterized in isolated aorta and mesenteric arteries in rats and mice. Our study was aimed at investigating the vascular effects of H₂S on human isolated mesenteric arteries and examining the underlying mechanisms involved. All experiments were performed on rings (4-8mm long) of human mesenteric arteries obtained from patients undergoing abdominal surgery. Ethical approval was obtained from the Ethics Committee of the University Hospital of the University of Florence (app. N. 2015/0024947). The effect of NaHS, an H₂S donor, was determined using noradrenaline pre-contracted human isolated mesenteric rings. NaHS evoked a concentration-dependent relaxation (EC₅₀ 57μM). In contrast, homocysteine, an endogenous precursor of H₂S, failed to affect human isolated mesenteric rings. Vasorelaxant response to NaHS was reduced by endothelium removal, application of the nitric oxide synthase inhibitor L-NAME and ODQ inhibitor of cyclic GMP. SQ 22536, an adenylate-cyclase inhibitor, failed to block NaHS-induced vasorelaxation. Inhibition of endogenous prostanoid production by indomethacin significantly reduced NaHS induced vasorelaxation. The role of potassium channels was also examined: blockers of the Ca²⁺-dependent potassium channel, charybdotoxin and apamin, failed to have any influence on the relaxant response to NaHS on this vascular tissue. In summary, H₂S induced relaxation of isolated rings of human mesenteric arteries. Endothelium-dependent related mechanisms with the stimulation of ATP-sensitive potassium channels represents important cellular mechanisms for H₂S effect on human mesenteric arteries.