Author + information
- Yang Jining,
- Si Daoyuan and
- Yang Ping
Amlodipine has been shown to improve endothelial cell dysfunction through anti-inflammatory mechanism, but whether S-amlodipine has a similar effect remains controversial. This study investigated relevant mechanisms of anti-inflammatory and the effects of S-amlodipine on vascular endothelial function.
Test rats (n=36, with spontaneous hypertension) were divided into 3 groups (n=12 each): group A treated with S-amlodipine, group B treated with amlodipine, group C as blank control. Other WKY rats (n=10) were chosen as group D (normal group). 10 weeks after treating, tumor necrosis factor (TNF-α) and interleukin 6 (IL-6) levels in their serum were detected by Elisa method.
Primary culture of umbilical vein endothelial cells (HUVECs) extracted from fresh fetal umbilical cord after cesarean section in pregnancy induced hypertension (diagnostic criteria for grade 2 of hypertension). Cells of generation 4-5 were selected for the experiment. Group E was treated with S-amlodipine(set up 5μM, 10μM, 20μM concentration of rug administration), group F was treated with amlodipine(set up 5μM, 10μM, 20μM concentration of rug administration), group G was set up as blank control. Elisa method was used to detect the level of IL-6 and TNF-α in the supernatant of culture medium in the presence and absence of S-amlodipine/amlodipine. It is reported that inflammatory status of cells is associated with the level of p38 MAPK and NF-κB. We extracted total protein of the cells in each group, and tested the expression of phosphor-p38 MAPK and phosphor-NF-κB subunit by Western blot.
(i) S-amlodipine has a similar effect with amlodipine in decreasing inflammatory stress in vivo and in vitro: the level of TNF-α and IL-6 decreased significantly in group A, group B, and group D compared with group C (p<0.05). There was no significant difference among group A, group B and group D (p>0.05). The level of TNF-α and IL-6 decreased significantly in group E and group F, compared with group G (p<0.05). The maximum inhibition effect was achieved at the concentration of 20μM (S-amlodipine) or 10μM (amlodipine). The inhibition effect has no significant difference between the two drugs (p>0.05), which indicated that S-amlodipine has the same effect to reduce the expression of inflammatory factors in hypertension as amlodipine.
(ii) S-amlodipine possess anti-inflammatory function through inhibiting p38 MAPK and NF-κB signaling pathways: compared with blank control group, treating with S-amlodipine and amlodipine can decrease the levels of phosphorylation of p38 MAPK and NF-κB subunits (p<0.05), which indicated that S-amlodipine can inhibit inflammation through p38 MAPK and NF-κB signaling pathways.
The reported data demonstrate that S-amlodipine has the effect to improve endothelial dysfunction in hypertension through anti-inflammatory mechanisms.