ArticleAmerican journal of physiology. Lung cellular and molecular physiology2010
Chronic hypoxia augments depolarization-induced Ca2+ sensitization in pulmonary vascular smooth muscle through superoxide-dependent stimulation of RhoA.
Article in American journal of physiology. Lung cellular and molecular physiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 62 citations in OpenAlex.
- Reactive Oxygen Species (ROS) in Metabolic Disease-Don't Shoot the Metabolic Messenger.International journal of molecular sciences · 2025Review
- Smooth muscle Acid-sensing ion channel 1a as a therapeutic target to reverse hypoxic pulmonary hypertension.Frontiers in molecular biosciences · 2022Article
- Acid-sensing ion channel 1 contributes to pulmonary arterial smooth muscle cell depolarization following hypoxic pulmonary hypertension.The Journal of physiology · 2021Article
- Vasoconstrictor Mechanisms in Chronic Hypoxia-Induced Pulmonary Hypertension: Role of Oxidant Signaling.Antioxidants (Basel, Switzerland) · 2020Review
- Altered Lipid Domains Facilitate Enhanced Pulmonary Vasoconstriction after Chronic Hypoxia.American journal of respiratory cell and molecular biology · 2020Article
- PKCβ and reactive oxygen species mediate enhanced pulmonary vasoconstrictor reactivity following chronic hypoxia in neonatal rats.American journal of physiology. Heart and circulatory physiology · 2020Article
- Augmented Pulmonary Vasoconstrictor Reactivity after Chronic Hypoxia Requires Src Kinase and Epidermal Growth Factor Receptor Signaling.American journal of respiratory cell and molecular biology · 2020Article
- Potential role of cartilage oligomeric matrix protein in the modulation of pulmonary arterial smooth muscle superoxide by hypoxia.American journal of physiology. Lung cellular and molecular physiology · 2019Article
- Twik-2Physiological reports · 2019Article
- Obesity and Pulmonary Hypertension.Current hypertension reports · 2018Review
- PLCγ1-PKCε-IPAmerican journal of physiology. Lung cellular and molecular physiology · 2018Article
- Actin polymerization contributes to enhanced pulmonary vasoconstrictor reactivity after chronic hypoxia.American journal of physiology. Heart and circulatory physiology · 2018Article
- Long-term high-altitude hypoxia influences pulmonary arterial L-type calcium channel-mediated CaAmerican journal of physiology. Regulatory, integrative and comparative physiology · 2018Article
- RhoA increases ASIC1a plasma membrane localization and calcium influx in pulmonary arterial smooth muscle cells following chronic hypoxia.American journal of physiology. Cell physiology · 2018Article
- Endothelial Cell Reactive Oxygen Species and CaAdvances in experimental medicine and biology · 2017Review
- Contribution of reactive oxygen species to the pathogenesis of pulmonary arterial hypertension.PloS one · 2017Article
- Predicted effects of nitric oxide and superoxide on the vasoactivity of the afferent arteriole.American journal of physiology. Renal physiology · 2015Article
- Mechanisms of NFATc3 activation by increased superoxide and reduced hydrogen peroxide in pulmonary arterial smooth muscle.American journal of physiology. Cell physiology · 2014Article
- Role of hypoxia-induced transglutaminase 2 in pulmonary artery smooth muscle cell proliferation.American journal of physiology. Lung cellular and molecular physiology · 2014Article
- Chronic hypoxia limits H2O2-induced inhibition of ASIC1-dependent store-operated calcium entry in pulmonary arterial smooth muscle.American journal of physiology. Lung cellular and molecular physiology · 2014Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Rho kinase (ROCK)-dependent vasoconstriction has been implicated as a major factor in chronic hypoxia (CH)-induced pulmonary hypertension. This component of pulmonary hypertension is associated with arterial myogenicity and increased vasoreactivity to receptor-mediated agonists and depolarizing stimuli resulting from ROCK-dependent myofilament Ca(2+) sensitization. On the basis of separate lines of evidence that CH increases pulmonary arterial superoxide (O(2)(-)) generation and that O(2)(-) stimulates RhoA/ROCK signaling in vascular smooth muscle (VSM), we hypothesized that depolarization-induced O(2)(-) generation mediates enhanced RhoA-dependent Ca(2+) sensitization in pulmonary VSM following CH. To test this hypothesis, we determined effects of the ROCK inhibitor HA-1077 and the O(2)(-)-specific spin trap tiron on vasoconstrictor reactivity to depolarizing concentrations of KCl in isolated lungs and Ca(2+)-permeabilized, pressurized small pulmonary arteries from control and CH (4 wk at 0.5 atm) rats. Using the same vessel preparation, we examined effects of CH on KCl-dependent VSM membrane depolarization and O(2)(-) generation using sharp electrodes and the fluorescent indicator dihydroethidium, respectively. Finally, using a RhoA-GTP pull-down assay, we investigated the contribution of O(2)(-) to depolarization-induced RhoA activation. We found that CH augmented KCl-dependent vasoconstriction through a Ca(2+) sensitization mechanism that was inhibited by HA-1077 and tiron. Furthermore, CH caused VSM membrane depolarization that persisted with increasing concentrations of KCl, enhanced KCl-induced O(2)(-) generation, and augmented depolarization-dependent RhoA activation in a O(2)(-)-dependent manner. These findings reveal a novel mechanistic link between VSM membrane depolarization, O(2)(-) generation, and RhoA activation that mediates enhanced myofilament Ca(2+) sensitization and pulmonary vasoconstriction following CH.
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