ArticleAntioxidants & redox signaling2013
Enhanced depolarization-induced pulmonary vasoconstriction following chronic hypoxia requires EGFR-dependent activation of NAD(P)H oxidase 2.
Article in Antioxidants & redox signaling, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 47 citations in OpenAlex.
- The Role of Piezo Ion Channels in Pulmonary Hypertension.Pulmonary circulation · 2026Review
- Reactive Oxygen Species (ROS) in Metabolic Disease-Don't Shoot the Metabolic Messenger.International journal of molecular sciences · 2025Review
- Hydroxy-Safflower Yellow A Mitigates Vascular Remodeling in Rat Pulmonary Arterial Hypertension.Drug design, development and therapy · 2024Article
- Contribution of Mitochondrial Reactive Oxygen Species to Chronic Hypoxia-Induced Pulmonary Hypertension.Antioxidants (Basel, Switzerland) · 2023Article
- Impact of Zinc on Oxidative Signaling Pathways in the Development of Pulmonary Vasoconstriction Induced by Hypobaric Hypoxia.International journal of molecular sciences · 2022Review
- Oxidative Stress and Diseases Associated with High-Altitude Exposure.Antioxidants (Basel, Switzerland) · 2022Review
- Oxidative Stress, Kinase Activation, and Inflammatory Pathways Involved in Effects on Smooth Muscle Cells During Pulmonary Artery Hypertension Under Hypobaric Hypoxia Exposure.Frontiers in physiology · 2021Review
- The pathophysiological nature of sarcomeres in trigger points in patients with myofascial pain syndrome: A preliminary study.European journal of pain (London, England) · 2020Article
- 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
- Intermittent Hypoxia Augments Pulmonary Vasoconstrictor Reactivity through PKCβ/Mitochondrial Oxidant Signaling.American journal of respiratory cell and molecular biology · 2020Article
- Cholesterol: A Novel Regulator of Vasoreactivity in Pulmonary Arteries.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
- Src and Epidermal Growth Factor Receptor: Novel Partners in Mediating Chronic Hypoxia-induced Pulmonary Artery Hypertension.American journal of respiratory cell and molecular biology · 2020Article
- Redox Regulation of Ion Channels and Receptors in Pulmonary Hypertension.Antioxidants & redox signaling · 2019Review
- Twik-2Physiological reports · 2019Article
- Calcitonin gene-related peptide hyperpolarizes mouse pulmonary artery endothelial tubes through KAmerican journal of physiology. Lung cellular and molecular physiology · 2018Article
- 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
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
aimsChronic hypoxia (CH) enhances depolarization-induced myofilament Ca(2+) sensitization and resultant pulmonary arterial constriction through superoxide (O(2)(-))-dependent stimulation of RhoA. Because NAD(P)H oxidase (NOX) has been implicated in the development of pulmonary hypertension, we hypothesized that vascular smooth muscle (VSM) depolarization increases NOX-derived O(2)(-) production leading to myofilament Ca(2+) sensitization and augmented vasoconstrictor reactivity following CH. As epidermal growth factor receptor (EGFR) mediates Rac1-dependent NOX activation in renal mesangial cells, we further sought to examine the role EGFR plays in this response.
resultsVasoconstrictor responses to depolarizing concentrations of KCl were greater in lungs isolated from CH (4 wk, 0.5 atm) rats compared to normoxic controls, and this effect of CH was abolished by the general NOX inhibitor, apocynin. CH similarly augmented KCl-induced vasoconstriction and O(2)(-) generation (assessed using the fluorescent indicator, dihydroethidium) in Ca(2+)-permeabilized, pressurized small pulmonary arteries. These latter responses to CH were prevented by general inhibition of NOX isoforms (apocynin, diphenylene iodonium), and by selective inhibition of NOX 2 (gp91ds-tat), Rac1 (NSC 23766), and EGFR (AG 1478). Consistent with these observations, CH increased KCl-induced EGFR phosphorylation, and augmented depolarization-induced Rac1 activation in an EGFR-dependent manner. INNOVATION: This study establishes a novel signaling axis in VSM linking membrane depolarization to contraction that is independent of Ca(2+) influx, and which mediates myofilament Ca(2+) sensitization in the hypertensive pulmonary circulation.
conclusionCH augments membrane depolarization-induced pulmonary VSM Ca(2+) sensitization and vasoconstriction through EGFR-dependent stimulation of Rac1 and NOX 2.
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