Apple polyphenol relieves hypoxia-induced pulmonary arterial hypertension via pulmonary endothelium protection and smooth muscle relaxation: In vivo and in vitro studies - 20/09/18
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Graphical abstract |
Highlights |
• | Apple polyphenol relieves mean pulmonary arterial pressure, pulmonary vessel resistance in hypoxia-induced pulmonary hypertension model of rat. |
• | After apple polyphenol administration, both endothelium intact and removed pulmonary vessel rings constricted by KCl or phenylephrine are relaxed. |
• | Apple polyphenol up-regulates Ca2+ efflux and K+ influx in pulmonary arterial smooth muscle cell. |
• | Apple polyphenol reduces pulmonary artery endothelium cell injury and apoptosis under hypoxia, and up-regulates NO level by enhancing endothelial nitric oxide synthase. |
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.
Le texte complet de cet article est disponible en PDF.Keywords : Apple polyphenol, Cation channel, Endothelium cell, Pulmonary arterial hypertension, Vasodilation, Pulmonary arterial smooth muscle cell
Plan
Vol 107
P. 937-944 - novembre 2018 Retour au numéro
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