The Effects Of Different Racemic Amlodipine On Rabbits Atherosclerosis Model

Objective： Amlodipine are chiral molecules. Racemic amlodipine iscomposed of S-amlodipine and R-amlodipine. However, if R-amlodipine hasbeneficial effects attracted the attention of many physicians. Even thoughsome scholars deduce R-amlodipine may have anti-atherosclerotic effects,until now there is only one study show that R-amlodipine releases nitric oxidefrom canine coronary microvessels in vitro. To clarify this question would bevery important to understand whether there is an essential difference on targetorgans protection effect between racemic amlodipine. To investigate theeffects of different racemic amlodipine on atherosclerosis, we introduced thestudy on the basis of atherosclerosis model by using high fat diet fed rabbits.Methods：30male New Zealand rabbits were randomized allocated in4groups：S-amlodipine group (group A), R-amlodipine group (group B),racemic amlodipine group (group C) and control group (group D). All therabbits in the4groups were fed on a high fat diet of2%cholesterol and5%lard oil for12weeks, and meanwhile, rabbits in group A, B, and C wereadministrated with S-amlodipine (2.5mg/d), R-amlodipine (2.5mg/d) andracemic amlodipine (5mg/d) for12weeks, respectively. Blood samples werecollected at the12th week after the beginning of the study. The concentrationof NO, ET-1, NOS, LDL-C, HDL-C and TG were measured. At the same time,analysis of plaque morphology and morphometry were quantified bycomputerized planimetry using the Qwin software (Leica Systems). Themacrophage positve area of the plaque were quantified by RAM-11usingimmunohistochemical stain, all data were show as±SD, comparisionamong multiple groups were performed by analysis of variance with ANOVA.When the variance analysis can not meet the conditions, Kruskal-Wallis testwas used to analysis the data, between groups were compared with SNK-q. All data analysis was performed by SPSS version13.0(SPSS inc, Chicago, USA).A p value <0.05was considered statistically significant.Results：1The effects of different racemic amlodipine on NO, ET-1, and NOS levelin the rabbits serum1.1Compare with that in the control group, NO level in the drug-therapygroup was not changed significantly (p＝0.256).1.2Compare with that in the control group, NOS in the drug-therapy groupwas not changed significantly (p＝0.313).1.3Compare with that in the control group, ET-1level in the drug-therapygroup was not changed significantly (p＝0.323).2The effects of different racemic amlodipine on external elastic membrancearea (EEMA), plaque area (PA), smooth muscle layer area (SA),vessel area stenosis rate (PA/EEMA) of the long time rabbits atherosclerosismodel.2.1Compare with that in the control group, EEMA in the drug-therapy groupwas reduced significantly (χ2＝21.18, p＜0.001). There was no differenceamong the drug-therapy groups (p＝0.577).2.2Compare with that in the control group, PA in the drug-therapy group wasreduced significantly (χ2＝19.35, p＜0.001). There was no difference amongthe drug-therapy groups (p＝0.213).2.3Compare with that in the control group, SA in the drug-therapy group wasreduced significantly (χ2＝23.75, p＜0.001). There was no difference amongthe drug-therapy groups (p＝0.735).2.4Compare with that in the control group, PA/EEMA in the drug-therapygroup was reduced significantly (χ2＝15.97, p＜0.001). There was nodifference among the drug-therapy groups (p＝0.164).3As depicted by RAM11immunohistochemistry, macrophage content wasmore extensive in plaques of control group, but did not got statisticallysignificant (F＝2.176, p＝0.116).Conclusion： 1Different racemic amlodipine did not change the concentration of NO,ET-1, NOS in the atherosclerotic rabbits serum.2Different racemic amlodipine can reduce atherosclerosis burden of theatherosclerotic rabbits.3Different racemic amlodipine did not reduce the macrophage content ofthe atherosclerosis plaques significantly.