Laboratory for Research in Neonatal Physiology, Department of Physiology, University of Tennessee Health Science Center, 894 Union Ave., Memphis, TN 38163, USA.
Am J Physiol Heart Circ Physiol. 2011 Feb;300(2):H440-7. doi: 10.1152/ajpheart.00722.2010. Epub 2010 Dec 3.
Hydrogen sulfide (H2S) is a gaseous signaling molecule that appears to be involved in numerous biological processes, including regulation of blood pressure and vascular tone. The present study is designed to address the hypothesis that H2S is a functionally significant, endogenous dilator in the newborn cerebrovascular circulation. In vivo experiments were conducted using newborn pigs with surgically implanted, closed, cranial windows. Topical application of H2S concentration-dependently (10(-6) to 2×10(-4) M) dilated pial arterioles. This dilation was blocked by glibenclamide (10(-6) M). L-cysteine, the substrate of the H2S-producing enzymes cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS), also dilated pial arterioles. The dilation to L-cysteine was blocked by the CSE inhibitor d,l-propargylglycine (PPG, 10 mM) but was unaffected by the CBS inhibitor amino-oxyacetate (AOA, 1 mM). Western blots detected CSE, but not CBS, in cerebral microvessels, whereas CBS is detected in brain parenchyma. Immunohistological CSE expression is predominantly vascular while CBS is expressed mainly in neurons and astrocytes. L-cysteine (5 mM) increased H2S concentration in cerebrospinal fluid (CSF), measured by GC-MS, from 561±205 to 2,783±818 nM before but not during treatment with PPG (1,030±70 to 622±78 nM). Dilation to hypercapnia was inhibited by PPG but not AOA. Hypercapnia increased CSF H2S concentration from 763±243 to 4,337±1789 nM before but not during PPG treatment (357±178 vs. 425±217 nM). These data show that H2S is a dilator of the newborn cerebral circulation and that endogenous CSE can produce sufficient H2S to decrease vascular tone. H2S appears to be a physiologically significant dilator in the cerebral circulation.
硫化氢 (H2S) 是一种气态信号分子，似乎参与了许多生物过程，包括血压和血管张力的调节。本研究旨在验证假设，即 H2S 是新生脑血管循环中具有功能意义的内源性扩张剂。在体内实验中，使用手术植入封闭颅窗的新生猪进行实验。H2S 浓度依赖性地（10(-6) 至 2×10(-4) M）扩张软脑膜小动脉。这种扩张被格列本脲 (10(-6) M) 阻断。L-半胱氨酸是 H2S 产生酶胱硫醚 γ-裂合酶 (CSE) 和胱硫醚 β-合酶 (CBS) 的底物，也扩张软脑膜小动脉。L-半胱氨酸的扩张被 CSE 抑制剂 d,l-炔丙基甘氨酸 (PPG，10 mM) 阻断，但不受 CBS 抑制剂氨基氧乙酸 (AOA，1 mM) 的影响。Western blot 在脑微血管中检测到 CSE，但未检测到 CBS，而 CBS 则在脑实质中检测到。免疫组织化学 CSE 表达主要在血管中，而 CBS 主要在神经元和星形胶质细胞中表达。L-半胱氨酸 (5 mM) 通过 GC-MS 测量，使脑脊液 (CSF) 中的 H2S 浓度从 561±205 增加到 2783±818 nM，而在 PPG 治疗期间则没有 (1030±70 增加到 622±78 nM)。PPG 抑制了对高碳酸血症的扩张，但 AOA 没有。高碳酸血症使 CSF H2S 浓度从 763±243 增加到 4337±1789 nM，而在 PPG 治疗期间则没有 (357±178 对 425±217 nM)。这些数据表明，H2S 是新生脑血管的扩张剂，内源性 CSE 可以产生足够的 H2S 来降低血管张力。H2S 似乎是脑血管循环中具有生理意义的扩张剂。
