Echinacoside induces rat pulmonary artery vasorelaxation by opening the NO-cGMP-PKG-BKca channels and reducing intracellular Ca2＋ levels  

作　　者：Xiang-yun GAI Yu-hai WEI Wei ZHANG Ta-na WUREN Ya-ping WANG Zhan-qiang LI Shou LIU Lan MA Dian-xiang LU Yi ZHOU Ri-li GE 

机构地区：[1]Department of Pharmacology, School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China [2]Research Center for High Altitude Medicine, Medical College of Qinghai University, Xining 810001, China [3]School of Pharmacy, Qinghai University for Nationalities, Xining 810007, China [4]Qinghai Entry-Exit Inspection and Quarantine Bureau, Xining 810001, China

出　　处：《Acta Pharmacologica Sinica》2015年第5期587-596,共10页中国药理学报（英文版）

摘　　要：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 （30-300μmol/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 ECso in endothelium-denuded rings. This effect was significantly blocked by L-NAME, TEA, and BaCI2. 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）.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 （30-300μmol/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 ECso in endothelium-denuded rings. This effect was significantly blocked by L-NAME, TEA, and BaCI2. 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）.

关 键 词：Tibetan herb ECHINACOSIDE pulmonary hypertension high altitude VASORELAXATION NO BKCA K^R artery ring pulmonaryarterial smooth muscle cells 

分 类 号：Q959.837[生物学—动物学] S858.31[农业科学—临床兽医学]