TY  - JOUR
A1  - Kosanovic, Djuro
A1  - Kojonazarov, Baktybek
A1  - Luitel, Himal
A1  - Dahal, Bhola K.
A1  - Sydykov, Akylbek
A1  - Cornitescu, Teodora
A1  - Janssen, Wiebke
A1  - Brandes, Ralf
A1  - Davie, Neil
A1  - Ghofrani, Hossein Ardeschir
A1  - Weißmann, Norbert
A1  - Grimminger, Friedrich
A1  - Seeger, Werner
A1  - Schermuly, Ralph T.
T1  - Therapeutic efficacy of TBC3711 in monocrotaline-induced pulmonary hypertension
T2  - Respiratory research
N2  - 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.
Y1  - 2011
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/22490
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30-113068
SN  - 1465-9921
SN  - 1465-993X
N1  - © 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.
VL  - 12
IS  - Art. 87
SP  - 1
EP  - 13
PB  - BioMed Central
CY  - London
ER  -