Ginsenoside-Rd, a new voltage-independent Ca2+ entry blocker, reverses basilar hypertrophic remodeling in stroke-prone renovascular hypertensive rats.
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.
Cai
Bing-Xiang
BX
Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, People's Republic of China.
Li
Xiao-Yan
XY
Chen
Jing-Hui
JH
Tang
Yong-Bo
YB
Wang
Guan-Lei
GL
Zhou
Jia-Guo
JG
Qui
Qin-Ying
QY
Guan
Yong-Yuan
YY
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology / Q000648:ultrastructure; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000098:blood supply; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004553:Electric Conductivity; D019332:Endothelin-1 / Q000494:pharmacology; D036145:Ginsenosides / Q000494:pharmacology*; D006978:Hypertension, Renovascular / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D046529:Microscopy, Electron, Transmission; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000209:etiology*
D002121:Calcium Channel Blockers; D019332:Endothelin-1; D036145:Ginsenosides; D002118:Calcium; C049863:ginsenoside Rd