Mohammed R, Provitera L, Cavallaro G, Lattuada D, Ercoli G, Mosca F, Villamor E
Department of Pediatrics, Maastricht University Medical Center (MUMC+), School for Oncology and Developmental Biology (GROW), University of Maastricht, Maastricht, the Netherlands.
Neonatal Intensive Care Unit, Department of Clinical Sciences and Community Health, Foundation IRCCS CA'Granda Ospedale Maggiore Polyclinic, University of Milan, Milan, Italy.
J Physiol Pharmacol. 2017 Oct;68(5):737-747.
Hydrogen sulfide (HS) 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 (NaS), which forms HS 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 HS 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 NaS (10-10) either at resting tone or during contraction evoked by serotonin or KCl. Similarly, the extraembryonic part of chicken allantoic artery did not respond to NaS. In contrast, NaS induced a concentration-dependent contraction in HUV rings under resting tone and a concentration-dependent relaxation when the HUV rings were contracted with serotonin (42 ± 5% relaxation) or KCl (12 ± 5% relaxation). NaS-induced contraction of HUV was impaired following removal of extracellular Ca, endothelial denudation, NO synthase inhibition (L-NAME), or soluble guanylate cyclase (sGC) inhibition (ODQ). NaS-induced relaxation of HUV was impaired by the K channel inhibitor glibenclamide. In conclusion, HS does not have vasomotor effects on HUA but induced contraction (mediated through inactivation of the NO/sGC axis) and relaxation (mediated through K channels) in HUV. Our data suggest a role for HS in the venous side of human umbilical circulation.
硫化氢（HS）最近已成为一种对心血管系统有多种作用的生物活性气体。我们旨在研究在溶液中形成HS的硫化钠（NaS）对人脐动脉（HUA）和静脉（HUV）环的血管舒缩作用。此外，我们通过免疫细胞化学检测了胱硫醚β-合酶（CBS）、胱硫醚裂解酶（CSE）和3-巯基丙酮酸硫转移酶（MPST）的表达和定位，这些酶负责内源性HS的产生。将人脐血管与鸡胚脐血管进行比较。HUA和HUV在内皮细胞和平滑肌细胞中均表达了针对CSE、CBS和3-MPST的强信号。然而，HUA环在静息张力下或由5-羟色胺或氯化钾诱发的收缩过程中对NaS（10-10）均无反应。同样，鸡尿囊动脉的胚外部分对NaS也无反应。相比之下，NaS在静息张力下可诱导HUV环产生浓度依赖性收缩，而当HUV环用5-羟色胺（舒张42±5%）或氯化钾（舒张12±5%）收缩时，NaS可诱导浓度依赖性舒张。去除细胞外钙、内皮剥脱、一氧化氮合酶抑制（L-NAME）或可溶性鸟苷酸环化酶（sGC）抑制（ODQ）后，NaS诱导的HUV收缩受到损害。K通道抑制剂格列本脲可损害NaS诱导的HUV舒张。总之，HS对HUA没有血管舒缩作用，但可诱导HUV收缩（通过NO/sGC轴失活介导）和舒张（通过K通道介导）。我们的数据表明HS在人脐循环的静脉侧发挥作用。
