Apple polyphenol relieves hypoxia-induced pulmonary arterial hypertension via pulmonary endothelium protection and smooth muscle relaxation: In vivo and in vitro studies

作者：Hua, Chunyan; Zhao, Jie; Wang, Heng; Chen, Fangzheng; Meng, Hanyan; Chen, Luowei; Zhang, Quanbo; Yan, Junjie; Yuan, Linbo^*

来源：Biomedicine & Pharmacotherapy, 2018, 107: 937-944.

DOI：10.1016/j.biopha.2018.08.080

• Apple polyphenol
• Cation channel
• Endothelium cell
• Pulmonary arterial hypertension
• Vasodilation
• Pulmonary arterial smooth muscle cell

Aim: This study aims to test the effect of apple polyphenol (APP) on hypoxia-induced pulmonary arterial hypertension (PAH) and explore its possible underlying mechanisms. @@@ Methods and results: Rats were treated with control, APP, hypoxia (8 h/d), hypoxia + APP. Mean pulmonary arterial pressure (mPAP) and pulmonary vessel resistance (PVR) were examined. Phenylephrine (PE)-pretreated pulmonary vessel rings were prepared for observation of APP administration. eNOS, sGC inhibitors (L-NAME, MB), Ca2+ channel blockers (NiCl2, Calhex231), K+ channel blockers (4-AP, 5-HD, TEA, BaCl2) were applied to pulmonary vessel rings and pulmonary arterial smooth muscle cell (PASMC). Flow cytometry analysis and CCK-8 assay were applied to detect apoptosis of pulmonary artery endothelium cell (PAEC). Caspase-3, NO, eNOS, iNOS were detected in PAEC. APP reversed mPAP and PVR elevation in vivo. Contraction of pulmonary vessel rings with/without endothelium induced by hypoxia were inhibited by APP. APP effect was hindered by L-NAME or MB, and could be reduced by K+ channel blockers. Further, APP was found to decrease cytosolic Ca2+ in PASMC and protect PAEC from apoptosis. In PAEC, Caspase-3, iNOS were decreased and NO, eNOS were increased after APP administration. @@@ Conclusions: APP reverses pulmonary vasoconstriction through enzyme expression and cation channel activities, thus has effects of PASMC relaxation and PAEC protection.

• 出版日期2018-11
• 单位浙江大学; 温州医科大学