Generation of oxidants by hypoxic human pulmonary and coronary smooth-muscle cells
Generation of oxidants by hypoxic human pulmonary and coronary smooth-muscle cells
复制标题
DOI：
10.1378/chest.07-2984
复制
发表时间：
2008-06-01
期刊：
影响因子：
9.6
通讯作者：
Eaton, John W.
中科院分区：
文献类型：
--
作者：
Mehta, Jinesh P.;Campian, Jian Li;Eaton, John W.
背景资料：由于非肺血管局部暴露于低氧导致血管舒张，因此低氧引起的肺血管收缩是不寻常的。研究表明，肺动脉平滑肌细胞可能对细胞内产生的活性氧（ROS）作出反应而松弛，并且在缺氧条件下ROS的产生减少。然而，其他工作者报道了在缺氧时人肺动脉平滑肌细胞（HPASMC）中ROS的产生增加。（Molecular Probes;尤金，俄勒冈州），我们估计了在常氧（20%）和急性缺氧（5%）下HPASMC和人冠状动脉平滑肌细胞（HCASMC）的融合原代培养物的ROS产生。所有三种测定系统均显示，在缺氧条件下，HPASMC的ROS产生降低，并且降低程度大于HCASMC的ROS产生降低。与HCASMC（<30%.Conclusions）相比，HPASMC在常氧时产生的ROS中，线粒体占60%以上，这些结果支持缺氧时HPASMC ROS产生减少而不是增加的结论。然而，由于缺氧期间HCASMC中ROS的产生也减少，因此血管张力发生相反变化的原因尚不明显。
Background: Pulmonary vasoconstriction in response to hypoxia is unusual inasmuch as local exposure of nonpulmonary vasculature to hypoxia results in vasodilation. It has been suggested that pulmonary artery smooth-muscle cells may relax in response to intracellular generation of reactive oxygen species (ROS) and that the production of ROS decreases under hypoxia. However, other workers report increased ROS production in human pulmonary artery smooth-muscle cells (HPASMC) during hypoxia.Methods: Using dihydrodichlorofluorescein diacetate, dihydroethidium, and Amplex Red (Molecular Probes; Eugene, OR), we estimated ROS generation by confluent primary cultures of HPASMC and human coronary artery smooth-muscle cells (HCASMC) under normoxia (20%) and acute hypoxia (5%).Results: All three assay systems showed that HPASMC production of ROS is decreased under hypoxia and to a greater extent than the decrease in ROS production by HCASMC. A substantially greater percentage of normoxic ROS production by HPASMC is mitochondrial (> 60%) compared to HCASMC (< 30%).Conclusions: These results support the conclusion that ROS generation decreases, rather than increases, in HPASMC during hypoxia. However, as ROS production also decreases in HCASMC during hypoxia, the reason for the opposite change in vascular tone is not yet apparent.