Chunyan Hua1, Jie Zhao2, Heng Wang3, Fangzheng Chen2, Hanyan Meng4, Luowei Chen2, Quanbo Zhang5, Junjie Yan6, Linbo Yuan7. 1. Basic Medicine School, Wenzhou Medical University, Wenzhou, PR China. 2. The First Clinical Medicine College, Wenzhou Medical University, Wenzhou, PR China. 3. Optometry & Ophthalmology College, Wenzhou Medical University, Wenzhou, PR China. 4. Zhejiang University School of Medicine, Zhejiang University, Hangzhou, PR China. 5. Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, PR China. 6. Pharmacy College, Wenzhou Medical University, Wenzhou, PR China. 7. Basic Medicine School, Wenzhou Medical University, Wenzhou, PR China. Electronic address: yuanlb731@126.com.
Abstract
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.
AIM: This study aims to test the effect of applepolyphenol (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.
Authors: Seyed Vahid Jasemi; Hosna Khazaei; Ina Yosifova Aneva; Mohammad Hosein Farzaei; Javier Echeverría Journal: Front Pharmacol Date: 2020-03-12 Impact factor: 5.810
Authors: José L Sánchez-Gloria; Horacio Osorio-Alonso; Abraham S Arellano-Buendía; Roxana Carbó; Adrián Hernández-Díazcouder; Carlos A Guzmán-Martín; Ivan Rubio-Gayosso; Fausto Sánchez-Muñoz Journal: Int J Mol Sci Date: 2020-07-08 Impact factor: 5.923