Vasorelaxation elicited by endogenous and exogenous hydrogen sulfide in mouse mesenteric arteries.

HS causes vasorelaxation however there is considerable heterogeneity in the reported pharmacological mechanism of this effect. This study examines the contribution of endogenously released HS in the regulation of vascular tone and the mechanism of HS-induced vasorelaxation in small resistance-like arteries. Mesenteric arteries from C57 and eNOS mice were mounted in myographs to record isometric force. Vasorelaxation responses to NaHS were examined in the presence of various inhibitors of vasorelaxation pathways. Expression and activity of the HS-producing enzyme, cystathionine-γ-lyase (CSE), were also examined. CSE was expressed in vascular smooth muscle and perivascular adipose cells from mouse mesenteric artery. The substrate for CSE, L-cysteine, caused a modest vasorelaxation (35%) in arteries from C57 mice and poor vasorelaxation (10%) in arteries from eNOS mice that was sensitive to the CSE inhibitor DL-propargylglycine. The fast HS donor, NaHS, elicited a full and biphasic vasorelaxation response in mesenteric arteries (EC (1) 8.7 μM, EC (2) 0.6 mM), which was significantly inhibited in eNOS vessels (P < 0.05), unaffected by endothelial removal, or blockers at any point in the NO via soluble guanylate cyclase and cGMP (NO-sGC-cGMP) vasorelaxation pathway. Vasorelaxation to NaHS was significantly inhibited by blocking K channels of the K and K subtypes and the Cl/HCO exchanger (P < 0.05). Further experiments showed that NaHS can significantly inhibit voltage-gated Ca channel function (P < 0.05). The vasorelaxant effect of HS in small resistance-like arteries is complex, involving eNOS, K channels, Cl/HCO exchanger, and voltage-gated Ca channels. CSE is present in the smooth muscle and periadventitial adipose tissue of these resistance-like vessels and can be activated to cause modest vasorelaxation under these in vitro conditions.