Therapeutic efficacy of TBC3711 in monocrotaline-induced pulmonary hypertension

Background: Endothelin-1 signalling plays an important role in pathogenesis of pulmonary hypertension. Although different endothelin-A receptor antagonists are developed, a novel therapeutic option to cure the disease is
Background: Endothelin-1 signalling plays an important role in pathogenesis of pulmonary hypertension. Although different endothelin-A receptor antagonists are developed, a novel therapeutic option to cure the disease is still needed. This study aims to investigate the therapeutic efficacy of the selective endothelin-A receptor antagonist TBC3711 in monocrotaline-induced pulmonary hypertension in rats.
Methods: Monocrotaline-injected male Sprague-Dawley rats were randomized and treated orally from day 21 to 35 either with TBC3711 (Dose: 30 mg/kg body weight/day) or placebo. Echocardiographic measurements of different hemodynamic and right-heart hypertrophy parameters were performed. After day 35, rats were sacrificed for invasive hemodynamic and right-heart hypertrophy measurements. Additionally, histologic assessment of pulmonary vascular and right-heart remodelling was performed.
Results: The novel endothelin-A receptor antagonist TBC3711 significantly attenuated monocrotaline-induced pulmonary hypertension, as evident from improved hemodynamics and right-heart hypertrophy in comparison with placebo group. In addition, muscularization and medial wall thickness of distal pulmonary vessels were ameliorated. The histologic evaluation of the right ventricle showed a significant reduction in fibrosis and cardiomyocyte size, suggesting an improvement in right-heart remodelling.
Conclusion: The results of this study suggest that the selective endothelin-A receptor antagonist TBC3711 demonstrates therapeutic benefit in rats with established pulmonary hypertension, thus representing a useful therapeutic approach for treatment of pulmonary hypertension.
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Metadaten
Author:Djuro Kosanovic, Baktybek Kojonazarov, Himal Luitel, Bhola K. Dahal, Akylbek Sydykov, Teodora Cornitescu, Wiebke Janssen, Ralf Peter Louis Brandes, Neil Davie, Hossein Ardeschir Ghofrani, Norbert Weißmann, Friedrich Grimminger, Werner Seeger, Ralph T. Schermuly
URN:urn:nbn:de:hebis:30-113068
DOI:http://dx.doi.org/10.1186/1465-9921-12-87
ISSN:1465-9921
ISSN:1465-993X
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=21699729
Parent Title (English):Respiratory research
Publisher:BioMed Central
Place of publication:London
Document Type:Article
Language:English
Date of Publication (online):2011/08/24
Date of first Publication:2011/12/01
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2011/08/24
Volume:12
Issue:Art. 87
Pagenumber:13
First Page:1
Last Page:13
Note:
© 2011 Kosanovic et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 
Source:Respiratory Research 2011, 12:87 doi: 10.1186/1465-9921-12-87 ; http://respiratory-research.com/content/12/1/87
HeBIS PPN:274740281
Institutes:Medizin
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 2.0

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