ArticleAmerican journal of physiology. Cell physiology2013
TRPV4 channel contributes to serotonin-induced pulmonary vasoconstriction and the enhanced vascular reactivity in chronic hypoxic pulmonary hypertension.
Article in American journal of physiology. Cell physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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53 citing papers in PubMed, 107 citations in OpenAlex.
- Transient receptor potential vanilloid 4 (TRPV4) channels mediate pulmonary surfactant protein A and D secretion.American journal of respiratory cell and molecular biology · 2026Article
- Discovery of a novel cannabidiol-derived transient receptor potential vanilloid 4 inhibitor to reduce pulmonary edema and lung vascular permeability in mice.Cellular & molecular biology letters · 2026Article
- Involvement of Nitric Oxide in TRPV4-Induced Relaxations of Mouse and Human Pulmonary Arteries.Biology · 2026Article
- The Potential Role of Calcium Channels in Pulmonary Hypertension.BioMed research international · 2026Review
- TRPV4 activation by core body temperature has multimodal functions in the central nervous system.The journal of physiological sciences : JPS · 2024Review
- TRPV4 Channel Modulators as Potential Drug Candidates for Cystic Fibrosis.International journal of molecular sciences · 2024Review
- Activation of renal vascular smooth muscle TRPV4 channels by 5-hydroxytryptamine impairs kidney function in neonatal pigs.Microvascular research · 2023Article
- Review
- Bidirectional TRP/L Type CaBiomolecules · 2023Article
- Novel Smooth Muscle CaCirculation · 2022Article
- Endothelial TRPV4 channels in lung edema and injury.Current topics in membranes · 2022Review
- Mechanosensitivity in Pulmonary Circulation: Pathophysiological Relevance of Stretch-Activated Channels in Pulmonary Hypertension.Biomolecules · 2021Review
- Endothelial pannexin 1-TRPV4 channel signaling lowers pulmonary arterial pressure in mice.eLife · 2021Article
- Halofuginone, a promising drug for treatment of pulmonary hypertension.British journal of pharmacology · 2021Article
- Serotonin-induced vascular permeability is mediated by transient receptor potential vanilloid 4 in the airways and upper gastrointestinal tract of mice.Laboratory investigation; a journal of technical methods and pathology · 2021Article
- Caveolar peroxynitrite formation impairs endothelial TRPV4 channels and elevates pulmonary arterial pressure in pulmonary hypertension.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- The Calcium Signaling Mechanisms in Arterial Smooth Muscle and Endothelial Cells.Comprehensive Physiology · 2021Article
- Piezo1 channels mediate trabecular meshwork mechanotransduction and promote aqueous fluid outflow.The Journal of physiology · 2021Article
- Role of Serosal TRPV4-Constituted SOCE Mechanism in Secretagogues-Stimulated Intestinal Epithelial Anion Secretion.Frontiers in pharmacology · 2021Article
- Renal vascular TRP channels.Current research in physiology · 2021Article
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8 authors at 5 institutions in 2 countries.
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Abstract
Transient receptor potential vanilloid 4 (TRPV4) is a mechanosensitive channel in pulmonary arterial smooth muscle cells (PASMCs). Its upregulation by chronic hypoxia is associated with enhanced myogenic tone, and genetic deletion of trpv4 suppresses the development of chronic hypoxic pulmonary hypertension (CHPH). Here we further examine the roles of TRPV4 in agonist-induced pulmonary vasoconstriction and in the enhanced vasoreactivity in CHPH. Initial evaluation of TRPV4-selective antagonists HC-067047 and RN-1734 in KCl-contracted pulmonary arteries (PAs) of trpv4(-/-) mice found that submicromolar HC-067047 was devoid of off-target effect on pulmonary vasoconstriction. Inhibition of TRPV4 with 0.5 μM HC-067047 significantly reduced the sensitivity of serotonin (5-HT)-induced contraction in wild-type (WT) PAs but had no effect on endothelin-1 or phenylephrine-activated response. Similar shift in the concentration-response curve of 5-HT was observed in trpv4(-/-) PAs, confirming specific TRPV4 contribution to 5-HT-induced vasoconstriction. 5-HT-induced Ca(2+) response was attenuated by HC-067047 in WT PASMCs but not in trpv4(-/-) PASMCs, suggesting TRPV4 is a major Ca(2+) pathway for 5-HT-induced Ca(2+) mobilization. Nifedipine also attenuated 5-HT-induced Ca(2+) response in WT PASMCs but did not cause further reduction in the presence of HC-067047, suggesting interdependence of TRPV4 and voltage-gated Ca(2+) channels in the 5-HT response. Chronic exposure (3-4 wk) of WT mice to 10% O2 caused significant increase in 5-HT-induced maximal contraction, which was partially reversed by HC-067047. In concordance, the enhancement of 5-HT-induced contraction was significantly reduced in PAs of CH trpv4(-/-) mice and HC-067047 had no further effect on the 5-HT induced response. These results suggest unequivocally that TRPV4 contributes to 5-HT-dependent pharmaco-mechanical coupling and plays a major role in the enhanced pulmonary vasoreactivity to 5-HT in CHPH.
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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.