Experimental Research on Effect of Strictosamide Injection on Cardiovascular System
10.11842/wst.2014.07.018
- VernacularTitle:异长春花苷内酰胺注射给药对心血管系统影响的实验研究
- Author:
Zhenzhen SU
;
Na LI
;
Liang CAO
;
Zhaoqing MENG
;
Wenjun LIU
;
Gang DING
;
Zhenzhong WANG
;
Wei XIAO
- Publication Type:Journal Article
- Keywords:
Strictosamide;
blood pressure;
ECG;
hERG;
Nav1 . 5
- From:
World Science and Technology-Modernization of Traditional Chinese Medicine
2014;(7):1558-1564
- CountryChina
- Language:Chinese
-
Abstract:
This study was aimed to investigate the effects of high-dose strictosamide injection on cardiovascular sys-tem of anesthetized beagle dogs and to examine the inhibition of strictosamide on ion channels in vitro. Indexes such as changes of systolic blood pressure (Sys), diastolic blood pressure (Dia), mean blood pressure (MBP), heart rate (HR), PR, QRS, QT, QTcb and QTcv at different time points before and after strictosamide injection in dogs were monitored by the polygraph system. The inhibition of strictosamide at different concentrations on hERG potassium channel in CHO-hERG cells and Nav1.5 sodium channel in HEK-293-Nav1.5 cells were measured by whole-cell patch-clamp method. The results showed that compared with the blank control group, Sys, Dia, MBP and HR were obviously declined 15 min after medication in the strictosamide (60, 18 mg·kg-1) group and the vehicle-control group (containing tween-80) (P < 0.05). After medication, all indexes were recovered. Compared to the vehicle-control group, there were no significant differences at different time points in each medication groups. Compared with the blank control group and before medication, the QT interval, QTcb and QTcv were significantly prolonged 15 min af-ter medication in the strictosamide (60, 18, 6 mg·kg-1) group and the vehicle-control group (P< 0.05). When medi-cation stopped, indexes were recovered at certain level. Compared with the vehicle-control group, there were no sig-nificant differences of QT interval, QTcb and QTcv of each medication group at different time points (P> 0.05). The inhibition of strictosamide on hERG potassium channel and Nav1.5 sodium channel were weak with IC50 values of 560.8 μM and > 900 μM, respectively, which were far greater than the positive controls. It was concluded that sin-gle, high-dose intravenous injection of strictosamide may lead to a lower blood pressure, a slower heart rate and a prolongation on the QT interval in beagle dogs, which returned to basal levels when medication stopped. It was spec-ulated that the reduction of blood pressure and the slowing of heart rate were related to tween-80 contained in the vehicle control group. No significant inhibitory effects were detected on hERG potassium channel and Nav1.5 sodium channel in vitro, which suggested that other mechanisms may be involved in strictosamide-induced QT interval pro-longation in animals.
