Region-Specific and Pregnancy-Enhanced Vasodilator Effects of Hydrogen Sulfide.

ABSTRACT

Hydrogen sulfide (H2S) is a cardiovascular signaling molecule that causes vasodilation in vascular smooth muscle cells, but its mechanism is unclear. We examined how H2S affects mesenteric and uterine arteries without endothelium in nonpregnant and pregnant rats and the underlying mechanisms. H2S donors GYY4137 and NaHS relaxed uterine arteries more than mesenteric arteries in both pregnant and nonpregnant rats. GYY4137 and NaHS caused greater relaxation in the uterine artery of pregnant versus nonpregnant rats. High extracellular K+ abolished NaHS relaxation in pregnant uterine arteries, indicating potassium channel involvement. NaHS relaxation was unaffected by voltage-gated potassium channel blockers, reduced by ATP-sensitive potassium channel blockers, and abolished by calcium-activated potassium (BKCa) channel blockers. Thiol-reductant dithiothreitol also prevented NaHS relaxation. Thus, H2S has region-specific and pregnancy-enhanced vasodilator effects in the uterine arteries, mainly mediated by BKCa channels and sulfhydration.