Ginsenoside-Rd, a new voltage-independent Ca2+ entry blocker, reverses basilar hypertrophic remodeling in stroke-prone renovascular hypertensive rats
Ginsenoside-Rd, a new voltage-independent Ca2+ entry blocker, reverses basilar hypertrophic remodeling in stroke-prone renovascular hypertensive rats
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DOI：
10.1016/j.ejphar.2009.01.033
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发表时间：
2009-03-15
影响因子：
5
通讯作者：
Guan, Yong-Yuan
中科院分区：
文献类型：
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作者：
Cai, Bing-Xiang;Li, Xiao-Yan;Guan, Yong-Yuan
三七总皂苷在我国临床上已用于治疗心血管疾病和中风。我们最近的研究发现人参皂苷-Rd（三七总皂苷的纯化成分）可以作为抑制剂，显着抑制电压依赖性 Ca2+ 进入。我们推断抑制电压依赖性 Ca2+ 进入可能有助于其脑血管益处，将人参皂苷-Rd 给予两肾、两夹 (2k2c) 易发生中风的高血压大鼠，以检查其对血压、脑血管重塑和新鲜分离的基底动脉血管平滑肌细胞 (BAVSMC) 中 Ca2+ 进入的影响。在培养的 BAVSMC 中评估了其对内皮素-1 诱导的 Ca2+ 进入和细胞增殖的影响。结果表明，在体内，人参皂苷-Rd 治疗可减轻 2k2c 高血压大鼠的基底动脉肥厚向内重塑，而不影响全身血压。在高血压的发展过程中，新分离的 BAVSMC 中受体操纵的 Ca2+ 通道 (ROCC)、钙池操纵的 Ca2+ 通道 (SOCC) 和电压依赖的 Ca2+ 通道 (VDCC) 介导的 Ca2+ 条目呈时间依赖性增加。人参皂苷-Rd 可逆转 SOCC- 或 ROCC- 的增加，但不能逆转 VDCC 介导的 Ca2+ 内流。在体外，人参皂苷-Rd 浓度依赖性地抑制内皮素-1 诱导的 BAVSMC 增殖和 Mn2+ 猝灭率，其浓度范围与抑制高血压期间 SOCC 或 ROCC 介导的 Ca2+ 内流增加所需的浓度范围相同。这些结果提供了体内证据，显示人参皂苷-Rd 治疗后高血压脑血管重塑的减弱。潜在机制可能与人参皂苷-Rd 对电压无关的 Ca2+ 内流和 BAVSMC 增殖的抑制作用有关，但与 VDCC 介导的 Ca2+ 内流无关。 (C) 2009 Elsevier B.V. 保留所有权利。
The total saponins of Panax notoginseng have been clinically used for the treatment of cardiovascular diseases and stroke in China. Our recent study has identified ginsenoside-Rd, a purified component of total saponins of P. notoginseng, as an inhibitor to remarkably inhibit voltage-in dependent Ca2+ entry. We deduced a hypothesis that the inhibition of voltage-independent Ca2+ entry might contribute to its cerebrovascular benefits, Ginsenoside-Rd was administered to two-kidney, two-clip (2k2c) stroke-prone hypertensive rats to examine its effects on blood pressure, cerebrovascular remodeling and Ca2+ entry in freshly isolated basilar arterial vascular smooth muscle cells (BAVSMCs). Its effects on endothelin-1 induced Ca2+ entry and cellular proliferation were assessed in cultured BAVSMCs. The results showed that, in vivo, ginsenoside-Rd treatment attenuated basilar hypertrophic inward remodeling in 2k2c hypertensive rats without affecting systemic blood pressure. During the development of hypertension, there were time-dependent increases in receptor-operated Ca2+ channel (ROCC)-, store-operated Ca2+ channel (SOCC)- and voltage dependent Ca2+ channel (VDCC)-mediated Ca2+ entries in freshly isolated BAVSMCs. Ginsenoside-Rd reversed the increase in SOCC- or ROCC- but not VDCC-mediated Ca2+ entry. In vitro, ginsenoside-Rd concentration-dependently inhibited endothelin-1 induced BAVSMC proliferation and Mn2+ quenching rate within the same concentration range as required for inhibition of increased SOCC- or ROCC-mediated Ca2+ entries during hypertension. These results provide in vivo evidence showing attenuation of hypertensive cerebrovascular remodeling after ginsenoside-Rd treatment. The underlying mechanism might be associated with inhibitory effects of ginsenoside-Rd on voltage-independent Ca2+ entry and BAVSMC proliferation, but not with VDCC-mediated Ca2+ entry. (C) 2009 Elsevier B.V. All rights reserved.