ArticleAmerican journal of respiratory cell and molecular biology2011
Tyrosine kinase inhibitors are potent acute pulmonary vasodilators in rats.
Article in American journal of respiratory cell and molecular biology, 2011. 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, 62 citations in OpenAlex.
- Positioning Imatinib for Pulmonary Arterial Hypertension: A Dose-Finding Phase 2 Study.American journal of respiratory and critical care medicine · 2025Trial
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- Viewing Pulmonary Arterial Hypertension Pathogenesis and Opportunities for Disease-Modifying Therapy Through the Lens of Biomass.JACC. Basic to translational science · 2024Review
- Current Overview of the Biology and Pharmacology in Sugen/Hypoxia-Induced Pulmonary Hypertension in Rats.Journal of aerosol medicine and pulmonary drug delivery · 2024Review
- Nebulisation of Paclitaxel, Sotatercept and Iloprost for pulmonary hypertension for lung cancer. FromJournal of Cancer · 2024Article
- AV-101, a novel inhaled dry-powder formulation of imatinib, in healthy adult participants: a phase 1 single and multiple ascending dose study.ERJ open research · 2023Article
- Imatinib attenuates reperfusion injury in a rat model of acute myocardial infarction.Basic research in cardiology · 2023Article
- Platelet-derived growth factor (PDGF)-BB regulates the airway tone via activation of MAP2K, thromboxane, actin polymerisation and CaRespiratory research · 2022Article
- Platelet-Derived Growth Factor Receptor Type α Activation Drives Pulmonary Vascular Remodeling Via Progenitor Cell Proliferation and Induces Pulmonary Hypertension.Journal of the American Heart Association · 2022Article
- Cooperativity between β-agonists and c-Abl inhibitors in regulating airway smooth muscle relaxation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Therapeutic Potential of Regorafenib-A Multikinase Inhibitor in Pulmonary Hypertension.International journal of molecular sciences · 2021Article
- The hypertensive effect of sorafenib is abolished by sildenafil.Cardio-oncology (London, England) · 2020Article
- The selective PGI2 receptor agonist selexipag ameliorates Sugen 5416/hypoxia-induced pulmonary arterial hypertension in rats.PloS one · 2020Article
- Tyrosine kinase inhibitors relax pulmonary arteries in human and murine precision-cut lung slices.Respiratory research · 2019Article
- PDGF-BB regulates the pulmonary vascular tone: impact of prostaglandins, calcium, MAPK- and PI3K/AKT/mTOR signalling and actin polymerisation in pulmonary veins of guinea pigs.Respiratory research · 2018Article
- Imatinib relaxes the pulmonary venous bed of guinea pigs.Respiratory research · 2017Article
- ROCK2 and MYLK variants under hypobaric hypoxic environment of high altitude associate with high altitude pulmonary edema and adaptation.The application of clinical genetics · 2015Article
- Article
- Activation of the EGFR/p38/JNK pathway by mitochondrial-derived hydrogen peroxide contributes to oxygen-induced contraction of ductus arteriosus.Journal of molecular medicine (Berlin, Germany) · 2014Article
- A novel vascular homing peptide strategy to selectively enhance pulmonary drug efficacy in pulmonary arterial hypertension.The American journal of pathology · 2014Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Tyrosine kinase inhibitors are promising for the treatment of severe pulmonary hypertension. Their therapeutic effects are postulated to be due to inhibition of cell growth-related kinases and attenuation of vascular remodeling. Their potential vasodilatory activities have not been explored. Vasorelaxant effects of the tyrosine kinase inhibitors imatinib, sorafenib, and nilotinib were examined in isolated pulmonary arterial rings from normal and pulmonary hypertensive rats. Phosphorylation of myosin light chain phosphatase and myosin light chain was assessed by Western blots. Acute hemodynamic effects of imatinib were tested in the pulmonary hypertensive rats. In normal pulmonary arteries, imatinib reversed serotonin- and U46619-induced contractions in a concentration-dependent and endothelium-independent manner. Sorafenib and nilotinib relaxed U46619-induced contraction. Imatinib inhibited activation of myosin phosphatase induced by U46619 in normal pulmonary arteries. All three tyrosine kinase inhibitors concentration-dependently and completely reversed the spontaneous contraction of hypertensive pulmonary arterial rings unmasked by inhibition of nitric oxide synthase. Acute intravenous administration of imatinib reduced high right ventricular systolic pressure in pulmonary hypertensive rats, with little effect on left ventricular systolic pressure and cardiac output. We conclude that tyrosine kinase inhibitors have potent pulmonary vasodilatory activity, which could contribute to their long-term beneficial effect against pulmonary hypertension. Vascular smooth muscle relaxation mediated via activation of myosin light chain phosphatase (Ca(2+) desensitization) appears to play a role in the imatinib-induced pulmonary vasodilation.
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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.