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

Autor: Gai XY; 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., Wei YH; Qinghai Entry-Exit Inspection and Quarantine Bureau, Xining 810001, China., Zhang W; Research Center for High Altitude Medicine, Medical College of Qinghai University, Xining 810001, China., Wuren TN; Research Center for High Altitude Medicine, Medical College of Qinghai University, Xining 810001, China., Wang YP; Research Center for High Altitude Medicine, Medical College of Qinghai University, Xining 810001, China., Li ZQ; Research Center for High Altitude Medicine, Medical College of Qinghai University, Xining 810001, China., Liu S; Research Center for High Altitude Medicine, Medical College of Qinghai University, Xining 810001, China., Ma L; Research Center for High Altitude Medicine, Medical College of Qinghai University, Xining 810001, China., Lu DX; Research Center for High Altitude Medicine, Medical College of Qinghai University, Xining 810001, China., Zhou Y; 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., Ge RL; 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.
Jazyk: angličtina
Zdroj: Acta pharmacologica Sinica [Acta Pharmacol Sin] 2015 May; Vol. 36 (5), pp. 587-96. Date of Electronic Publication: 2015 Apr 13.
DOI: 10.1038/aps.2014.126
Abstrakt: 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 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.
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 (BKCa and KIR).
Databáze: MEDLINE
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