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Respiratory Research
Published in: Respiratory Research 1/2011

Open Access 01-12-2011 | Research

Therapeutic efficacy of TBC3711 in monocrotaline-induced pulmonary hypertension

Authors: Djuro Kosanovic, Baktybek Kojonazarov, Himal Luitel, Bhola K Dahal, Akylbek Sydykov, Teodora Cornitescu, Wiebke Janssen, Ralf P Brandes, Neil Davie, Hossein A Ghofrani, Norbert Weissmann, Friedrich Grimminger, Werner Seeger, Ralph T Schermuly

Published in: Respiratory Research | Issue 1/2011

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Abstract

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.
Appendix
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Metadata
Title
Therapeutic efficacy of TBC3711 in monocrotaline-induced pulmonary hypertension
Authors
Djuro Kosanovic
Baktybek Kojonazarov
Himal Luitel
Bhola K Dahal
Akylbek Sydykov
Teodora Cornitescu
Wiebke Janssen
Ralf P Brandes
Neil Davie
Hossein A Ghofrani
Norbert Weissmann
Friedrich Grimminger
Werner Seeger
Ralph T Schermuly
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2011
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/1465-9921-12-87

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