Gaseous molecules controlling metabolic systems

缺氧引起的脑血流量增加对脑功能至关重要，但其调节的信号系统尚不清楚。我们报告了一种新的途径介导缺氧诱导的脑血管舒张的研究监测血管处置小脑切片以及在完整的小鼠大脑采用双光子活体激光扫描显微镜。在这一级联反应中，缺氧通过与胱硫醚形成的硫化氢（H_2S）的协同作用而使脑血管舒张。合成酶（CBS）和由血红素加氧酶（HO）-2产生的一氧化碳（CO）。缺氧可减少HO-2产生CO的能力。组成型CO生理性抑制CBS，因此缺氧导致H_2S水平增加，介导毛细血管前小动脉的血管舒张。HO-2或CBS靶向缺失的小鼠显示对缺氧的血管反应受损。因此，在完整的成年大脑皮层HO-2-null小鼠，成像质谱显示受损的能力，以维持ATP水平缺氧。

Enhancement of cerebral blood flow by hypoxia is critical for brain function, but signaling systems underlying its regulation have been unclear. We report a novel pathway mediating hypoxia-induced cerebral vasodilation in studies monitoring vascular disposition in cerebellar slices as well as in intact mouse brains employing two-photon intravital laser scanning microscopy. In this cascade, hypoxia elicits cerebral vasodilation via the coordinate actions of hydrogen sulfide(H_2S) formed by cystathionine.-synthase(CBS) and carbon monoxide(CO) generated by heme oxygenase(HO)-2. Hypoxia diminishes CO generation by HO-2, an oxygen(O_2) sensor. The constitutive CO physiologically inhibits CBS, so that hypoxia leads to increased levels of H_2S that mediate the vasodilation of pre-capillary arterioles. Mice with targeted deletion of HO-2 or CBS display impaired vascular responses to hypoxia. Thus, in intact adult brain cerebral cortex of HO-2-null mice, imaging mass spectrometry reveals an impaired ability to maintain ATP levels on hypoxia.