Vasoconstrictor Mechanisms in Chronic Hypoxia-Induced Pulmonary Hypertension: Role of Oxidant Signaling.
Vasoconstrictor Mechanisms in Chronic Hypoxia-Induced Pulmonary Hypertension: Role of Oxidant Signaling.
复制标题
DOI：
10.3390/antiox9100999
复制
发表时间：
2020-10-15
期刊：
影响因子：
--
通讯作者：
Jernigan NL
中科院分区：
文献类型：
--
作者：
Yan S;Resta TC;Jernigan NL
慢性低氧暴露后肺循环阻力升高导致肺动脉高压。通过钙依赖性和钙致敏机制增强的肺血管收缩促成了这一病理过程。活性氧（ROS），由于酶的产生增加和/或清除减少，参与增强肺动脉收缩，通过加强钙内流以及激活肌丝敏化，从而介导肺动脉高压的发展。在这里，我们回顾了慢性缺氧对肺血管内ROS来源的影响，包括NADPH氧化酶，线粒体，解偶联内皮型一氧化氮合酶，黄嘌呤氧化酶，单胺氧化酶和功能失调的超氧化物歧化酶。我们还总结了ROS诱导的各种Ca 2+和K+通道参与调节Ca 2+内流的功能改变，以及负责肌丝Ca 2+敏感性的Rho激酶。各种抗氧化剂已被证明在肺动脉高压的动物模型中具有有益的治疗效果，支持ROS在肺动脉高压发展中的作用。更好地了解ROS增强血管收缩的机制将有助于评估抗氧化剂治疗肺动脉高压的疗效。
Elevated resistance of pulmonary circulation after chronic hypoxia exposure leads to pulmonary hypertension. Contributing to this pathological process is enhanced pulmonary vasoconstriction through both calcium-dependent and calcium sensitization mechanisms. Reactive oxygen species (ROS), as a result of increased enzymatic production and/or decreased scavenging, participate in augmentation of pulmonary arterial constriction by potentiating calcium influx as well as activation of myofilament sensitization, therefore mediating the development of pulmonary hypertension. Here, we review the effects of chronic hypoxia on sources of ROS within the pulmonary vasculature including NADPH oxidases, mitochondria, uncoupled endothelial nitric oxide synthase, xanthine oxidase, monoamine oxidases and dysfunctional superoxide dismutases. We also summarize the ROS-induced functional alterations of various Ca2+ and K+ channels involved in regulating Ca2+ influx, and of Rho kinase that is responsible for myofilament Ca2+ sensitivity. A variety of antioxidants have been shown to have beneficial therapeutic effects in animal models of pulmonary hypertension, supporting the role of ROS in the development of pulmonary hypertension. A better understanding of the mechanisms by which ROS enhance vasoconstriction will be useful in evaluating the efficacy of antioxidants for the treatment of pulmonary hypertension.
登录
查看更多内容
DOI：
10.1016/j.bbamcr.2005.01.008
发表时间：
2005-08-15
影响因子：
5.1
作者：
Andrey, F;Tsintsadze, T;Krishtal, O
通讯作者：
Krishtal, O
影响因子：
4.2
作者：
Armstead, WM
通讯作者：
Armstead, WM
DOI：
10.1152/ajplung.00098.2012
发表时间：
2012-11-01
影响因子：
4.9
作者：
Afolayan, Adeleye J.;Eis, Annie;Konduri, Girija G.
通讯作者：
Konduri, Girija G.
影响因子：
5.7
作者：
Ahmed, Mohamed N.;Zhang, Yinzhong;Miller, Edmund J.
通讯作者：
Miller, Edmund J.
DOI：
10.1152/ajplung.00155.2014
发表时间：
2015-04-01
影响因子：
4.9
作者：
Alhawaj, Raed;Patel, Dhara;Wolin, Michael S.
通讯作者：
Wolin, Michael S.