Gai Xiang-yun, Wei Yu-hai, Zhang Wei, Wuren Ta-na, Wang Ya-ping, Li Zhan-qiang, Liu Shou, Ma Lan, Lu Dian-xiang, Zhou Yi, Ge Ri-li
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.
Qinghai Entry-Exit Inspection and Quarantine Bureau, Xining 810001, China.
Acta Pharmacol Sin. 2015 May;36(5):587-96. doi: 10.1038/aps.2014.126. Epub 2015 Apr 13.
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.
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 Ca(2+) levels were measured in cultured rat pulmonary arterial smooth muscle cells (PASMCs) using Fluo 4-AM.
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 Ca(2+)-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.
ECH suppresses NE-induced contraction of rat pulmonary artery via reducing intracellular Ca(2+) levels, and induces its relaxation through the NO-cGMP pathway and opening of K(+) channels (BKCa and KIR).
高海拔地区出现的持续性肺血管收缩可导致肺动脉高压（PH）。本研究的主要目的是研究松果菊苷（ECH），一种来自藏药短管兔耳草和管花肉苁蓉的苯乙醇苷，对肺动脉的血管舒张作用及其潜在机制。
从雄性Wistar大鼠获取的肺动脉环悬挂于充满Krebs-Henseleit溶液的器官浴槽中，使用力传感器测量等长张力。使用Fluo 4-AM测量培养的大鼠肺动脉平滑肌细胞（PASMCs）中的细胞内Ca(2+)水平。
ECH（30 - 300 μmol/L）以浓度依赖性方式舒张去甲肾上腺素（NE）预收缩的大鼠肺动脉，完整内皮和去内皮环均可观察到这种作用，但去内皮环中的最大反应明显较低且EC50较高。L-NAME、TEA和BaCl2可显著阻断这种作用。然而，IMT、4-AP和Gli并未抑制ECH诱导的舒张。在无细胞外Ca(2+)条件下，用100和300 μmol/L ECH处理的环中最大收缩分别降至24.54%±2.97%和10.60%±2.07%。在细胞外钙内流条件下，用30、100和300 μmol/L ECH处理的环中最大收缩分别降至112.42%±7.30%、100.29%±8.66%和74.74%±4.95%。用Fluo 4-AM加载细胞后，用ECH（100 μmol/L）处理的细胞的平均荧光强度低于用NE处理的细胞。
ECH通过降低细胞内Ca(2+)水平抑制NE诱导的大鼠肺动脉收缩，并通过NO-cGMP途径和K(+)通道（BKCa和KIR）开放诱导其舒张。
