PDF(Pubmed)
Abstract：
Vasodilation in response to low oxygen (O2) tension (hypoxic vasodilation) is an essential homeostatic response of systemic arteries that facilitates O2 supply to tissues according to demand. However, how blood vessels react to O2 deficiency is not well understood. A common belief is that arterial myocytes are O2-sensitive. Supporting this concept, it has been shown that the activity of myocyte L-type Ca2+channels, the main ion channels responsible for vascular contractility, is reversibly inhibited by hypoxia, although the underlying molecular mechanisms have remained elusive. Here, we show that genetic or pharmacological disruption of mitochondrial electron transport selectively abolishes O2 modulation of Ca2+ channels and hypoxic vasodilation. Mitochondria function as O2 sensors and effectors that signal myocyte Ca2+ channels due to constitutive Hif1α-mediated expression of specific electron transport subunit isoforms. These findings reveal the acute O2-sensing mechanisms of vascular cells and may guide new developments in vascular pharmacology.
摘要：
响应于低氧（O2）张力的血管舒张（低氧血管舒张）是全身动脉的基本稳态反应，可根据需求促进组织的O2供应。然而,血管对O2缺乏的反应尚不清楚。一个普遍的信念是动脉肌细胞对O2敏感。支持这个概念，已经表明，肌细胞L型Ca2+通道的活性，负责血管收缩的主要离子通道，被缺氧可逆地抑制，尽管潜在的分子机制仍然难以捉摸。这里,我们表明线粒体电子传递的遗传或药理学破坏选择性地消除了Ca2通道的O2调节和低氧性血管舒张。由于组成型Hif1α介导的特定电子传递亚基亚型的表达，线粒体充当O2传感器和效应子，向心肌细胞Ca2通道发出信号。这些发现揭示了血管细胞的急性O2感应机制，并可能指导血管药理学的新进展。
