Journal article

Publication year: 2011

Journal: Respiratory Research

Volume number: 12

ISSN: 1465-993X

eISSN: 1465-9921

Open access status: Gold

DOI Link: https://doi.org/10.1186/1465-9921-12-87

Publisher: BioMed Central

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.

Harvard Citation style: Kosanovic, D., Kojonazarov, B., Luitel, H., Dahal, B., Sydykov, A., Cornitescu, T., et al. (2011) Therapeutic efficacy of TBC3711 in monocrotaline-induced pulmonary hypertension, Respiratory Research, 12, Article 87. https://doi.org/10.1186/1465-9921-12-87

APA Citation style: Kosanovic, D., Kojonazarov, B., Luitel, H., Dahal, B., Sydykov, A., Cornitescu, T., Janssen, W., Brandes, R., Davie, N., Ghofrani, H., Weissmann, N., Grimminger, F., Seeger, W., & Schermuly, R. (2011). Therapeutic efficacy of TBC3711 in monocrotaline-induced pulmonary hypertension. Respiratory Research. 12, Article 87. https://doi.org/10.1186/1465-9921-12-87