ArticleThe Journal of clinical investigation2012
Hypoxic pulmonary vasoconstriction requires connexin 40-mediated endothelial signal conduction.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 144 citations in OpenAlex.
- Arterial tracing-based technique for rapid purification of pulmonary arterial smooth muscle cells from rat lungs.Physiological reports · 2026Article
- Vacuum-stabilized lung window enables real-time and simultaneous imaging of vascular and calcium responses to hypoxia in vivo.Respiratory research · 2026Article
- An improved precision-cut lung slices technique for pulmonary vasoconstriction.Respiratory research · 2026Article
- Inhibition of TRPV4 Regulates Mitophagy Through the Sirt1/FoxO1 Signaling Pathway To Alleviate Acute Lung Injury.Inflammation · 2026Article
- Connexin-hemichannels-mediated ATP release causes lung injury following chlorine inhalation.American journal of physiology. Cell physiology · 2025Article
- Pulmonary vascular remodeling in Fra-2 transgenic mice is driven by type 2 inflammation and accompanied by pulmonary vascular hyperresponsiveness.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Studying the Pulmonary Endothelium in Health and Disease: An Official American Thoracic Society Workshop Report.American journal of respiratory cell and molecular biology · 2024Article
- Hypoxia in the pulmonary vein increases pulmonary vascular resistance independently of oxygen in the pulmonary artery.Animal models and experimental medicine · 2024Article
- The conducted vasomotor response and the principles of electrical communication in resistance arteries.Physiological reviews · 2024Review
- Impact of aging on vascular ion channels: perspectives and knowledge gaps across major organ systems.American journal of physiology. Heart and circulatory physiology · 2023Review
- Pathophysiology and pathogenic mechanisms of pulmonary hypertension: role of membrane receptors, ion channels, and CaPhysiological reviews · 2023Review
- Article
- Endothelialitis, Microischemia, and Intussusceptive Angiogenesis in COVID-19.Cold Spring Harbor perspectives in medicine · 2022Review
- Pannexin 1: a novel regulator of acute hypoxic pulmonary vasoconstriction.Cardiovascular research · 2022Article
- Functional implications of microvascular heterogeneity for oxygen uptake and utilization.Physiological reports · 2022Review
- Perioperative Pulmonary Atelectasis: Part I. Biology and Mechanisms.Anesthesiology · 2022Review
- New Insights into Pulmonary Hypertension: A Role for Connexin-Mediated Signalling.International journal of molecular sciences · 2021Review
- COVID-19 is a systemic vascular hemopathy: insight for mechanistic and clinical aspects.Angiogenesis · 2021Review
- Analysis of flow resistance in the pulmonary arterial circulation: implications for hypoxic pulmonary vasoconstriction.Journal of applied physiology (Bethesda, Md. : 1985) · 2021Article
- Hypoxic pulmonary vasoconstriction as a regulator of alveolar-capillary oxygen flux: A computational model of ventilation-perfusion matching.PLoS computational biology · 2021Article
7 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 12 institutions in 9 countries.
Funding
Abstract
Hypoxic pulmonary vasoconstriction (HPV) is a physiological mechanism by which pulmonary arteries constrict in hypoxic lung areas in order to redirect blood flow to areas with greater oxygen supply. Both oxygen sensing and the contractile response are thought to be intrinsic to pulmonary arterial smooth muscle cells. Here we speculated that the ideal site for oxygen sensing might instead be at the alveolocapillary level, with subsequent retrograde propagation to upstream arterioles via connexin 40 (Cx40) endothelial gap junctions. HPV was largely attenuated by Cx40-specific and nonspecific gap junction uncouplers in the lungs of wild-type mice and in lungs from mice lacking Cx40 (Cx40-/-). In vivo, hypoxemia was more severe in Cx40-/- mice than in wild-type mice. Real-time fluorescence imaging revealed that hypoxia caused endothelial membrane depolarization in alveolar capillaries that propagated to upstream arterioles in wild-type, but not Cx40-/-, mice. Transformation of endothelial depolarization into vasoconstriction involved endothelial voltage-dependent α1G subtype Ca2+ channels, cytosolic phospholipase A2, and epoxyeicosatrienoic acids. Based on these data, we propose that HPV originates at the alveolocapillary level, from which the hypoxic signal is propagated as endothelial membrane depolarization to upstream arterioles in a Cx40-dependent manner.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.