Ginsenoside-Rd, a new voltage-independent Ca2+ entry blocker, reverses basilar hypertrophic remodeling in stroke-prone renovascular hypertensive rats

被引：51

作者：

Cai, Bing-Xiang ^{[1
]}

Li, Xiao-Yan ^{[1
]}

Chen, Jing-Hui ^{[2
]}

Tang, Yong-Bo ^{[1
]}

Wang, Guan-Lei ^{[1
]}

Zhou, Jia-Guo ^{[1
]}

Qui, Qin-Ying ^{[1
]}

Guan, Yong-Yuan ^{[1
]}

机构：

[1] Sun Yat Sen Univ, Dept Pharmacol, Zhongshan Sch Med, Guangzhou 510089, Guangdong, Peoples R China

[2] Sun Yat Sen Univ, Affiliated Hosp 3, Dept Anesthesiol, Guangzhou 510089, Guangdong, Peoples R China

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 2009年 / 606卷 / 1-3期

基金：

中国国家自然科学基金;

关键词：

Ginsenoside-Rd; Hypertension (kidney); Cerebrovascular remodeling; Receptor-operated; Store-operated; Ca2+ channels; SMOOTH-MUSCLE-CELLS; TRP CHANNELS; PROLIFERATION; RECEPTOR; ENDOTHELIN-1; ARTERIOLES; MYOCYTES;

D O I：

10.1016/j.ejphar.2009.01.033

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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.

引用

页码：142 / 149

页数：8

共 24 条

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