Y-X Wang1, M-L Liu, B Zhang, E-Q Fu, Z-C Li. 1. Department of Pathology and Pathophysiology, Fourth Military Medical University, Xi'an, P. R. China. lizhic@fmmu.edu.cn.
Abstract
OBJECTIVE: The aim of this study was to investigate the mechanism of fasudil alleviating hypoxic pulmonary hypertension (HPH). MATERIALS AND METHODS: A total of 50 Sprague-Dawley rats were randomized into control, model and fasudil intervention groups. Hemodynamic and pulmonary pathomorphology data were collected using Powerlab system and hematoxylin and eosin staining. The protein expression of Ang-(1-7) was detected by immunohistochemical staining and ELISA assay in vivo or in vitro. Western blot was utilized to observe the protein expression of ACE2 and HIF-1α in vitro. RESULTS: Fasudil treatment repressed the elevation of RVSP, RV/(LV+S), attenuated the pulmonary vascular structure remodeling (PVSR) of pulmonary arterioles induced by chronic hypoxia, and stabilized the expression of Ang-(1-7) in vivo and in vitro. In addition, experiments consistently indicated an escalation of ACE2 and a reduction of HIF-1α. CONCLUSIONS: Our results suggest that fasudil can effectively attenuate PVSR and PH. The underlying mechanism may partially up-regulated Ang-(1-7) and ACE2, and lessened HIF-1α.
OBJECTIVE: The aim of this study was to investigate the mechanism of fasudil alleviating hypoxic pulmonary hypertension (HPH). MATERIALS AND METHODS: A total of 50 Sprague-Dawley rats were randomized into control, model and fasudil intervention groups. Hemodynamic and pulmonary pathomorphology data were collected using Powerlab system and hematoxylin and eosin staining. The protein expression of Ang-(1-7) was detected by immunohistochemical staining and ELISA assay in vivo or in vitro. Western blot was utilized to observe the protein expression of ACE2 and HIF-1α in vitro. RESULTS:Fasudil treatment repressed the elevation of RVSP, RV/(LV+S), attenuated the pulmonary vascular structure remodeling (PVSR) of pulmonary arterioles induced by chronic hypoxia, and stabilized the expression of Ang-(1-7) in vivo and in vitro. In addition, experiments consistently indicated an escalation of ACE2 and a reduction of HIF-1α. CONCLUSIONS: Our results suggest that fasudil can effectively attenuate PVSR and PH. The underlying mechanism may partially up-regulated Ang-(1-7) and ACE2, and lessened HIF-1α.
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