tailieunhanh - Báo cáo y học: " Therapeutic efficacy of TBC3711 in monocrotaline-induced pulmonary hypertension"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học 'Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài: " Therapeutic efficacy of TBC3711 in monocrotaline-induced pulmonary hypertension. | Kosanovic et al. Respiratory Research 2011 12 87 http content 12 1 87 RESPIRATORY RESEARCH RESEARCH Open Access Therapeutic efficacy of TBC3711 in monocrotaline-induced pulmonary hypertension 1 1111 1 Djuro Kosanovic Baktybek Kojonazarov Himal Luitel Bhola K Dahal Akylbek Sydykov Teodora Cornitescu Wiebke Janssen2 Ralf P Brandes3 Neil Davie4 Hossein A Ghofrani1 Norbert Weissmann1 Friedrich Grimminger1 Werner Seeger1 2 and Ralph T Schermuly1 2 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 .