Document Detail

Improvement of bleomycin-induced pulmonary hypertension and pulmonary fibrosis by the endothelin receptor antagonist Bosentan.
MedLine Citation:
PMID:  19931426     Owner:  NLM     Status:  MEDLINE    
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.
Stephan Schroll; Michael Arzt; Daniela Sebah; Martin Nüchterlein; Friedrich Blumberg; Michael Pfeifer
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Publication Detail:
Type:  Journal Article     Date:  2009-11-28
Journal Detail:
Title:  Respiratory physiology & neurobiology     Volume:  170     ISSN:  1878-1519     ISO Abbreviation:  Respir Physiol Neurobiol     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2010-02-04     Completed Date:  2010-04-16     Revised Date:  2013-06-18    
Medline Journal Info:
Nlm Unique ID:  101140022     Medline TA:  Respir Physiol Neurobiol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  32-6     Citation Subset:  IM    
Copyright Information:
Copyright 2009 Elsevier B.V. All rights reserved.
Department of Internal Medicine II, Pneumology, University of Regensburg, Regensburg, Germany.
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MeSH Terms
Analysis of Variance
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
Physical Conditioning, Animal / physiology
Pulmonary Fibrosis / chemically induced,  drug therapy*
Rats, Wistar
Sulfonamides / therapeutic use*
Time Factors
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 0/Antihypertensive Agents; 0/Ctgf protein, rat; 0/Sulfonamides; 11056-06-7/Bleomycin; 139568-91-5/Connective Tissue Growth Factor; 9007-34-5/Collagen; Q326023R30/bosentan

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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