Echinacoside induces rat pulmonary artery vasorelaxation by opening the NO-cGMP-PKG-BK_(Ca) channels and reducing intracellular Ca~(2+) levels
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文摘
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 Ca~(2+) 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 EC_(50) in endothelium-denuded rings. This effect was significantly blocked by L-NAME, TEA, and BaCl_2 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. Conclusion: 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 (BK_(Ca) and K_(IR)).
来源
Acta Pharmacologica Sinica
,2015,36(5):587-596 【核心库】
DOI
10.1038/aps.2014.126
关键词
Tibetan herb
;
echinacoside
;
pulmonary hypertension
;
high altitude
;
vasorelaxation
;
NO
;
BK_(Ca)
;
K_(IR)
;
artery ring
;
pulmonary arterial smooth muscle cells
地址
1.
Department of Pharmacology, School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, 110016
2.
Qinghai Entry-Exit Inspection and Quarantine Bureau, Xining, 810001
3.
Research Center for High Altitude Medicine, Medical College of Qinghai University, Xining, 810001
语种
英文
文献类型
研究性论文
ISSN
1671-4083
学科
药学
基金
supported by the National Program on Key Basic Research Project of China
;
国家自然科学基金
;
the Program of International Science and Technology Cooperation of China
;
国家自然科学基金
;
the Key Laboratories Development Program of Qinghai Province
;
Qinghai-Utah Joint Research Key Lab for High Altitude Medicine
;
the Ministry of Education New Century Outstanding Talents Support Program of China
;
the Natural Science Foundation of Qinghai
文献收藏号
CSCD:5425432
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