Abstract
Aim:
Sustained pulmonary vasoconstriction as experienced at high altitude can lead to pulmonary hypertension (PH). The main purpose of this study is to investigate the vasorelaxant effect of echinacoside (ECH), a phenylethanoid glycoside from the Tibetan herb Lagotis brevituba Maxim and Cistanche tubulosa, on the pulmonary artery and its potential mechanism.
Methods:
Pulmonary arterial rings obtained from male Wistar rats were suspended in organ chambers filled with Krebs-Henseleit solution, and isometric tension was measured using a force transducer. Intracellular Ca2+ levels were measured in cultured rat pulmonary arterial smooth muscle cells (PASMCs) using Fluo 4-AM.
Results:
ECH (30–300 μmol/L) relaxed rat pulmonary arteries precontracted by noradrenaline (NE) in a concentration-dependent manner, and this effect could be observed in both intact endothelium and endothelium-denuded rings, but with a significantly lower maximum response and a higher EC50 in endothelium-denuded rings. This effect was significantly blocked by L-NAME, TEA, and BaCl2. However, IMT, 4-AP, and Gli did not inhibit ECH-induced relaxation. Under extracellular Ca2+-free conditions, the maximum contraction was reduced to 24.54%±2.97% and 10.60%±2.07% in rings treated with 100 and 300 μmol/L of ECH, respectively. Under extracellular calcium influx conditions, the maximum contraction was reduced to 112.42%±7.30%, 100.29%±8.66%, and 74.74%±4.95% in rings treated with 30, 100, and 300 μmol/L of ECH, respectively. After cells were loaded with Fluo 4-AM, the mean fluorescence intensity was lower in cells treated with ECH (100 μmol/L) than with NE.
Conclusion:
ECH suppresses NE-induced contraction of rat pulmonary artery via reducing intracellular Ca2+ levels, and induces its relaxation through the NO-cGMP pathway and opening of K+ channels (BKCa and KIR).
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Acknowledgements
We thank Liang YANG and her laboratory (Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China) for their help in detecting the intracellular calcium concentration of rat PASMCs.
This project is supported by the National Program on Key Basic Research Project of China (No 2012CB518200), the Program of International Science and Technology Cooperation of China (No 2011DFA32720), the National Natural Science Foundation of China (No 31160219), the Key Laboratories Development Program of Qinghai Province (No 2013-Z-Y05, No 2014-Z-Y-30, and No 2014-Z-Y-07), Qinghai-Utah Joint Research Key Lab for High Altitude Medicine, the National Natural Science Foundation of China (No 81160012), the Ministry of Education New Century Outstanding Talents Support Program of China (No NCET-12-1022) and the National Natural Science Foundation of Qinghai (No 2012-Z-915Q).
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Gai, Xy., Wei, Yh., Zhang, W. et al. Echinacoside induces rat pulmonary artery vasorelaxation by opening the NO-cGMP-PKG-BKCa channels and reducing intracellular Ca2+ levels. Acta Pharmacol Sin 36, 587–596 (2015). https://doi.org/10.1038/aps.2014.126
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DOI: https://doi.org/10.1038/aps.2014.126
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