Ginsenoside Rb1 Attenuates Agonist-Induced Contractile Response via Inhibition of Store-Operated Calcium Entry in Pulmonary Arteries of Normal and Pulmonary Hypertensive Rats
Ginsenoside Rb1 Attenuates Agonist-Induced Contractile Response via Inhibition of Store-Operated Calcium Entry in Pulmonary Arteries of Normal and Pulmonary Hypertensive Rats
复制标题
人参皂苷 Rb1 通过抑制正常和肺动脉高压大鼠肺动脉中钙库操纵的钙进入来减弱激动剂诱导的收缩反应
DOI：
10.1159/000373966
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发表时间：
2015-01-01
影响因子：
--
通讯作者：
Lin, Mo-Jun
中科院分区：
文献类型：
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作者：
Wang, Rui-Xing;He, Rui-Lan;Lin, Mo-Jun
背景：肺动脉高压（Pulmonary hypertension， PH）以血管持续收缩、血管反应性增强和血管重构为特征，可导致右心衰和死亡。尽管有几种治疗方法，但许多形式的酸碱度仍然是无法治愈的。人参皂苷Rb1是人参的主要活性成分，对心血管系统具有多种药理作用，可抑制MCT诱导的右心肥厚。然而，其对肺血管功能与PH的影响尚不清楚。方法：我们研究了人参皂苷Rb1对内皮素-1 （ET-1）诱导的肺动脉（PAs）收缩和慢性缺氧（CH）和mct诱导的ph下肺动脉平滑肌细胞（PASMCs）储存性Ca2+进入（SOCE）的血管松弛作用。结果：人参皂苷Rb1诱导ET-1诱导的PA收缩的浓度依赖性松弛。硝苯地平不影响血管舒张作用，但SOCE阻滞剂Gd3+可消除血管舒张作用。人参皂苷Rb1抑制环吡唑酸（CPA）诱导的PA收缩，以及CPA激活的PASMCs阳离子进入和Ca2+瞬态。在CH和mct处理大鼠的PA和PASMCs中，ET-1和cpa诱导的收缩、cpa激活的阳离子进入和Ca2+瞬态均增强；人参皂苷Rb1消除了增强的应答。结论：人参皂苷Rb1通过抑制SOCE减轻et -1诱导的收缩反应，并能有效拮抗肺血管反应性增强。Copyright (C) 2015 S. Karger AG, Basel
Background: Pulmonary hypertension (PH) is characterized by sustained vasoconstriction, enhanced vasoreactivity and vascular remodeling, which leads to right heart failure and death. Despite several treatments are available, many forms of PH are still incurable. Ginsenoside Rb1, a principle active ingredient of Panax ginseng, exhibits multiple pharmacological effects on cardiovascular system, and suppresses monocrotaline (MCT)-induced right heart hypertrophy. However, its effect on the pulmonary vascular functions related to PH is unknown. Methods: We examined the vasorelaxing effects of ginsenoside Rb1 on endothelin-1 (ET-1) induced contraction of pulmonary arteries (PAs) and store-operated Ca2+ entry (SOCE) in pulmonary arterial smooth muscle cells (PASMCs) from chronic hypoxia (CH) and MCT-induced PH. Results: Ginsenoside Rb1 elicited concentration-dependent relaxation of ET-1-induced PA contraction. The vasorelaxing effect was unaffected by nifedipine, but abolished by the SOCE blocker Gd3+. Ginsenoside Rb1 suppressed cyclopiazonic acid (CPA)-induced PA contraction, and CPA-activated cation entry and Ca2+ transient in PASMCs. ET-1 and CPA-induced contraction, and CPA-activated cation entry and Ca2+ transients were enhanced in PA and PASMCs of CH and MCT-treated rats; the enhanced responses were abolished by ginsenoside Rb1. Conclusion: Ginsenoside Rb1 attenuates ET-1-induced contractile response via inhibition of SOCE, and it can effectively antagonize the enhanced pulmonary vasoreactivity in PH. Copyright (C) 2015 S. Karger AG, Basel