| Improvement of bleomycin-induced pulmonary hypertension and pulmonary fibrosis by the endothelin receptor antagonist Bosentan. | |
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MedLine Citation:
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PMID: 19931426 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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RATIONALE: There is evidence that endothelin plays a key role in the development of pulmonary hypertension (PH) in pulmonary fibrosis (PF). However, the functional consequence of the unselective endothelin receptor antagonist Bosentan in PH and PF has not yet been studied. Therefore, we investigated the effects of Bosentan on the development of PH in the model of Bleomycin-induced PF in rats. METHODS: Adult male Wistar rats were randomly assigned to the following groups: untreated animals (controls), Bleomycin-induced PF (Bleomycin) and Bleomycin-induced PF treated with Bosentan (Bleomycin+Bosentan). Exercise capacity was evaluated by treadmill exercise testing. PH was assessed by right ventricular systolic pressure (RVSP) and right ventricular hypertrophy. For quantification of PF the hydroxyproline content in lung tissue (HPC) was measured. RESULTS: Compared to controls, animals with Bleomycin-induced PF showed a significant reduction in exercise capacity (44% vs. 100%), significantly higher RVSP (65 mmHg vs. 23 mmHg), significantly more right ventricular hypertrophy (0.55 vs. 0.24) and significantly higher HPC (60.5 vs. 14.8). Bosentan treatment in animals with Bleomycin-induced PF resulted in significantly greater exercise capacity (98% vs. 44%) and a trend towards lower RVSP (52 mmHg vs. 65 mmHg), significantly less right ventricular hypertrophy (0.34 vs. 0.55) and significantly lower HPC (16.7 vs. 60.5) compared to untreated Bleomycin-induced PF. CONCLUSION: Application of Bosentan in Bleomycin rats resulted in significantly higher exercise capacity as a result of improvements in PH and PF. |
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Authors:
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Stephan Schroll; Michael Arzt; Daniela Sebah; Martin N?chterlein; Friedrich Blumberg; Michael Pfeifer |
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Publication Detail:
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Type: Journal Article Date: 2009-11-28 |
Journal Detail:
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Title: Respiratory physiology & neurobiology Volume: 170 ISSN: 1878-1519 ISO Abbreviation: Respir Physiol Neurobiol Publication Date: 2010 Jan |
Date Detail:
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Created Date: 2010-02-04 Completed Date: 2010-04-16 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101140022 Medline TA: Respir Physiol Neurobiol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 32-6 Citation Subset: IM |
Copyright Information:
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Copyright 2009 Elsevier B.V. All rights reserved. |
Affiliation:
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Department of Internal Medicine II, Pneumology, University of Regensburg, Regensburg, Germany. stephan.schroll@klinik.uni-regensburg.de |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Analysis of Variance Animals Antibiotics, Antineoplastic / adverse effects Antihypertensive Agents / therapeutic use* Bleomycin / adverse effects Collagen / metabolism Connective Tissue Growth Factor / genetics, metabolism Disease Models, Animal Hemodynamics / drug effects Hypertension, Pulmonary / chemically induced, drug therapy* Hypertrophy, Right Ventricular / drug therapy, pathology Lung / drug effects, metabolism Male Physical Conditioning, Animal / physiology Pulmonary Fibrosis / chemically induced, drug therapy* Rats Rats, Wistar Sulfonamides / therapeutic use* Time Factors |
| Chemical | |
Reg. No./Substance:
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0/Antibiotics, Antineoplastic; 0/Antihypertensive Agents; 0/Ctgf protein, rat; 0/Sulfonamides; 11056-06-7/Bleomycin; 139568-91-5/Connective Tissue Growth Factor; 147536-97-8/bosentan; 9007-34-5/Collagen |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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