Vasoconstrictor Mechanisms in Chronic Hypoxia-Induced Pulmonary Hypertension: Role of Oxidant Signaling
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 resul...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-10-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/9/10/999 |
| _version_ | 1797550840048779264 |
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| author | Simin Yan Thomas C. Resta Nikki L. Jernigan |
| author_facet | Simin Yan Thomas C. Resta Nikki L. Jernigan |
| author_sort | Simin Yan |
| collection | DOAJ |
| description | 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 Ca<sup>2+</sup> and K<sup>+</sup> channels involved in regulating Ca<sup>2+</sup> influx, and of Rho kinase that is responsible for myofilament Ca<sup>2+</sup> 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. |
| first_indexed | 2024-03-10T15:35:09Z |
| format | Article |
| id | doaj.art-0f312789aa2047868255740c2681ee7a |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T15:35:09Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-0f312789aa2047868255740c2681ee7a2023-11-20T17:16:01ZengMDPI AGAntioxidants2076-39212020-10-0191099910.3390/antiox9100999Vasoconstrictor Mechanisms in Chronic Hypoxia-Induced Pulmonary Hypertension: Role of Oxidant SignalingSimin Yan0Thomas C. Resta1Nikki L. Jernigan2Vascular Physiology Group, Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USAVascular Physiology Group, Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USAVascular Physiology Group, Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USAElevated 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 Ca<sup>2+</sup> and K<sup>+</sup> channels involved in regulating Ca<sup>2+</sup> influx, and of Rho kinase that is responsible for myofilament Ca<sup>2+</sup> 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.https://www.mdpi.com/2076-3921/9/10/999reactive oxygen speciespulmonary vasoconstrictioncalcium influxcalcium sensitizationpulmonary hypertensionchronic hypoxia |
| spellingShingle | Simin Yan Thomas C. Resta Nikki L. Jernigan Vasoconstrictor Mechanisms in Chronic Hypoxia-Induced Pulmonary Hypertension: Role of Oxidant Signaling Antioxidants reactive oxygen species pulmonary vasoconstriction calcium influx calcium sensitization pulmonary hypertension chronic hypoxia |
| title | Vasoconstrictor Mechanisms in Chronic Hypoxia-Induced Pulmonary Hypertension: Role of Oxidant Signaling |
| title_full | Vasoconstrictor Mechanisms in Chronic Hypoxia-Induced Pulmonary Hypertension: Role of Oxidant Signaling |
| title_fullStr | Vasoconstrictor Mechanisms in Chronic Hypoxia-Induced Pulmonary Hypertension: Role of Oxidant Signaling |
| title_full_unstemmed | Vasoconstrictor Mechanisms in Chronic Hypoxia-Induced Pulmonary Hypertension: Role of Oxidant Signaling |
| title_short | Vasoconstrictor Mechanisms in Chronic Hypoxia-Induced Pulmonary Hypertension: Role of Oxidant Signaling |
| title_sort | vasoconstrictor mechanisms in chronic hypoxia induced pulmonary hypertension role of oxidant signaling |
| topic | reactive oxygen species pulmonary vasoconstriction calcium influx calcium sensitization pulmonary hypertension chronic hypoxia |
| url | https://www.mdpi.com/2076-3921/9/10/999 |
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