Yadav Pankaj, Chen Dong-Bao, Kumar Sathish
Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin, United States of America.
Department of Obstetrics & Gynecology, University of California, Irvine, California, United States of America.
Obstet Gynecol Res. 2023;6(4):309-316. doi: 10.26502/ogr0145. Epub 2023 Dec 22.
Hydrogen sulfide (HS) is a cardiovascular signaling molecule that causes vasodilation in vascular smooth muscle cells, but its mechanism is unclear. We examined how HS affects mesenteric and uterine arteries without endothelium in nonpregnant and pregnant rats and the underlying mechanisms. HS 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 (BK) channel blockers. Thiol-reductant dithiothreitol also prevented NaHS relaxation. Thus, HS has region-specific and pregnancy-enhanced vasodilator effects in the uterine arteries, mainly mediated by BK channels and sulfhydration.
硫化氢(HS)是一种心血管信号分子,可引起血管平滑肌细胞血管舒张,但其机制尚不清楚。我们研究了HS如何影响未怀孕和怀孕大鼠无内皮的肠系膜动脉和子宫动脉及其潜在机制。在怀孕和未怀孕大鼠中,HS供体GYY4137和NaHS对子宫动脉舒张作用比对肠系膜动脉更强。与未怀孕大鼠相比,GYY4137和NaHS对怀孕大鼠子宫动脉舒张作用更大。高细胞外钾消除了怀孕子宫动脉中NaHS的舒张作用,表明钾通道参与其中。NaHS的舒张作用不受电压门控钾通道阻滞剂影响,被ATP敏感性钾通道阻滞剂减弱,并被钙激活钾(BK)通道阻滞剂消除。硫醇还原剂二硫苏糖醇也可阻止NaHS的舒张作用。因此,HS在子宫动脉中具有区域特异性和怀孕增强的血管舒张作用,主要由BK通道和巯基化介导。