Cai Bing-Xiang, Li Xiao-Yan, Chen Jing-Hui, Tang Yong-Bo, Wang Guan-Lei, Zhou Jia-Guo, Qui Qin-Ying, Guan Yong-Yuan
Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, People's Republic of China.
Eur J Pharmacol. 2009 Mar 15;606(1-3):142-9. doi: 10.1016/j.ejphar.2009.01.033. Epub 2009 Jan 29.
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-independent Ca(2+) entry. We deduced a hypothesis that the inhibition of voltage-independent Ca(2+) 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 Ca(2+) entry in freshly isolated basilar arterial vascular smooth muscle cells (BAVSMCs). Its effects on endothelin-1 induced Ca(2+) 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 Ca(2+) channel (ROCC)-, store-operated Ca(2+) channel (SOCC)- and voltage dependent Ca(2+) channel (VDCC)-mediated Ca(2+) entries in freshly isolated BAVSMCs. Ginsenoside-Rd reversed the increase in SOCC- or ROCC- but not VDCC-mediated Ca(2+) entry. In vitro, ginsenoside-Rd concentration-dependently inhibited endothelin-1 induced BAVSMC proliferation and Mn(2+) quenching rate within the same concentration range as required for inhibition of increased SOCC- or ROCC-mediated Ca(2+) 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 Ca(2+) entry and BAVSMC proliferation, but not with VDCC-mediated Ca(2+) entry.
三七总皂苷在中国已被临床用于治疗心血管疾病和中风。我们最近的研究已确定三七总皂苷的纯化成分人参皂苷-Rd是一种抑制剂，可显著抑制非电压依赖性Ca(2+)内流。我们推断出一个假设，即抑制非电压依赖性Ca(2+)内流可能有助于其脑血管益处。将人参皂苷-Rd给予两肾双夹（2k2c）易中风高血压大鼠，以检查其对血压、脑血管重塑以及新鲜分离的基底动脉血管平滑肌细胞（BAVSMC）中Ca(2+)内流的影响。在培养的BAVSMC中评估其对内皮素-1诱导的Ca(2+)内流和细胞增殖的影响。结果表明，在体内，人参皂苷-Rd治疗可减轻2k2c高血压大鼠的基底肥厚性内向重塑，而不影响全身血压。在高血压发展过程中，新鲜分离的BAVSMC中受体操纵性Ca(2+)通道（ROCC）、储存操纵性Ca(2+)通道（SOCC）和电压依赖性Ca(2+)通道（VDCC）介导的Ca(2+)内流呈时间依赖性增加。人参皂苷-Rd可逆转SOCC或ROCC介导的Ca(2+)内流增加，但不能逆转VDCC介导的Ca(2+)内流增加。在体外，人参皂苷-Rd在与抑制高血压期间SOCC或ROCC介导的Ca(2+)内流增加所需浓度相同的范围内，浓度依赖性地抑制内皮素-1诱导的BAVSMC增殖和Mn(2+)淬灭率。这些结果提供了体内证据，表明人参皂苷-Rd治疗后高血压性脑血管重塑得到减轻。其潜在机制可能与人参皂苷-Rd对非电压依赖性Ca(2+)内流和BAVSMC增殖的抑制作用有关，而与VDCC介导的Ca(2+)内流无关。
