School of Medical Sciences and Health Innovations Research Institute, RMIT University, PO Box 71, Bundoora 3083, Melbourne, Victoria, Australia.
Naunyn Schmiedebergs Arch Pharmacol. 2012 Oct;385(10):991-1002. doi: 10.1007/s00210-012-0779-2. Epub 2012 Jul 17.
Hydrogen sulfide (H(2)S) is an endogenous mediator with peripheral vasorelaxant effects; however, the mechanism of H(2)S-induced vasorelaxation in cerebral blood vessels has not been extensively studied. Vasorelaxation studies were performed on middle cerebral arteries from male Sprague Dawley rats using wire myography. Immunofluorescence staining was used to detect the presence of the H(2)S-producing enzyme cystathionine-γ-lyase (CSE). CSE was present in the endothelium and smooth muscle of middle cerebral arteries. The CSE substrate, L-cysteine, induced vasorelaxation that was sensitive to the CSE inhibitor DL-propargylglycine. This relaxation was independent of endothelium, suggesting that H(2)S was produced in the vascular smooth muscle. The H(2)S donor, sodium hydrogen sulfide (NaHS; 0.1-3.0 mM) produced concentration-dependent relaxation, which was unaffected by endothelium removal. Nifedipine (3 μM) significantly reduced the maximum relaxation elicited by NaHS. Inhibiting potassium (K(+)) conductance with 50 mM K(+) significantly attenuated NaHS-induced relaxation, however, selective blockers of ATP sensitive (K(ATP)), calcium sensitive (K(Ca)), voltage dependent (K(V)), or inward rectifier (K(ir)) channels alone or in combination did not affect the response to NaHS. 4,4-diisothiocyanatostilbene-2,2-disulfonic acid (DIDS; 300 μM) caused a significant rightward shift of the NaHS concentration-response curve, but this effect could not be explained by inhibition of Cl(-) channels or Cl(-)/HCO (3)(-) exchange, as selective blockade of these mechanisms had no effect. These findings suggest endogenous H(2)S can regulate cerebral vascular function. The H(2)S-mediated relaxation of middle cerebral arteries is DIDS sensitive and partly mediated by inhibition of L-type calcium channels, with an additional contribution by K channels but not K(ATP), K(Ca), K(V), or K(ir) subtypes.
硫化氢（H2S）是一种内源性介质，具有外周血管舒张作用；然而，H2S 诱导脑血管舒张的机制尚未得到广泛研究。使用wire myography 对雄性 Sprague Dawley 大鼠的大脑中动脉进行血管舒张研究。免疫荧光染色用于检测 H2S 产生酶胱硫醚-γ-裂解酶（CSE）的存在。CSE 存在于大脑中动脉的内皮细胞和平滑肌中。CSE 底物 L-半胱氨酸诱导的血管舒张对 CSE 抑制剂 DL-丙炔基甘氨酸敏感。这种舒张不受内皮细胞影响，提示 H2S 是在血管平滑肌中产生的。H2S 供体，硫氢化钠（NaHS；0.1-3.0 mM）产生浓度依赖性舒张，内皮细胞去除对其无影响。硝苯地平（3 μM）显著降低了 NaHS 引起的最大舒张。用 50 mM K+抑制钾（K+）电导显著减弱了 NaHS 诱导的舒张，但 ATP 敏感（KATP）、钙敏感（KCa）、电压依赖性（KV）或内向整流（Kir）通道的选择性阻滞剂单独或联合使用均不影响对 NaHS 的反应。4,4-二异硫氰酸基二苯乙烯-2,2-二磺酸（DIDS；300 μM）使 NaHS 浓度-反应曲线发生明显右移，但这种作用不能用 Cl-通道或 Cl--HCO3-交换的抑制来解释，因为这些机制的选择性阻断对无影响。这些发现表明内源性 H2S 可以调节脑血管功能。大脑中动脉的 H2S 介导的舒张对 DIDS 敏感，部分由 L 型钙通道的抑制介导，另外还有 K 通道的贡献，但不是 KATP、KCa、KV 或 Kir 亚类。
