The Effects Of Different Enantiomer Amlodipine On Rabbits Atherosclerosis

Objective：Many studies suggested that amlodipine can prevent againstthe development of atherosclerosis (AS), but which clinical physicians andpharmacists concerned is the anti-atherosclerotic effect of amlodipine fromS-amlodipine or R-amlodipine. Some scholars reckon that the anti-atherosclerotic effect of amlodipine come from R-amlodipine, but until nowonly one in vitro study showed that R-amlodipine released nitric oxide fromcanine coronary microvessels. Meanwhile, some experts believe that theR-amlodipine can induce edema, dizziness, as well as many other adversereactions. To clarify this question would be very important to understandwhether there is an essential difference on the effect of target organs protectionand anti-hypertension between different enantiomer amlodipine. To investigatethe effects of different enantiomer amlodipine on atherosclerosis, we designedthe study on the basis of AS model rabbits by feeding high fat diet.Methods：30healthy male New Zealand rabbits(from the LaboratoryAnimal Centre of HeBei Medical University) were randomized allocated into4groups: control group (Group A), S-amlodipine feeding group (Group B),R-amlodipine feeding group (Group C) and racemic amlodipine feeding group(Group D). All the rabbits in the4groups were fed on a high fat diet of1%cholesterol and2%lard oil for8weeks. Meanwhile, rabbits in Group B, C,and D were administrated with S-amlodipine (2.5mg/d), R-amlodipine(2.5mg/d) or racemic amlodipine (5mg/d) for8weeks, respectively. Bloodsamples of all the rabbits were collected at the baseline,4thweek, and8thweekof the study. The concentration of total cholesterol (TC), low-densitylipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C)and triglyceride (TG) were measured. Meanwhile, analysis of plaquemorphology and morphometry were quantified by computerized planimetry by the Qwin software (Leica Systems). The macrophage positive area of theplaque was quantified by RAM-11using immuno-histochemical stain. All datawere showed as±SD. Comparisions among groups were performed byANOVA. When the variance analysis can not meet the conditions,Kruskal-Wallis test was used. Between groups were compared with SNK-q.Analysis of all data was performed by SPSS version13.0(SPSS, Chicago,USA). A P value <0.05was considered statistically significant.Results：1The effects of different enantiomer amlodipine on TC, LDL-C, HDL-Cand TG level in the blood serum of rabbits at baseline,4thweek and8thweek.Based on ANOVA, there is no significant difference among each groupabout the concentration of TC, LDL-C, HDL-C, and TG at baseline,4thweekand8thweek of the study.2The effect of different enantiomer amlodipine on AS model rabbitsMCP-1positive area and external elastic membrance area (EEMA) ratio.The plaque MCP-1positive area and EEMA ratios of four groups are asfollows:0.17±0.06,0.07±0.05,0.14±0.09, and0.05±0.03. The varianceanalysis can not meet the conditions, the nonparametric test (Kruskal-Wallis)statistical analysis show that the MCP-1positive area and EEMA ratio hasstatistically significant difference (χ2=12.271，P=0.007) between each group.Compared with Group A, MCP-1positive area and EEMA ratio in Group Band Group D were decreased significantly (P=0.02，P=0.001), respectively.MCP-1positive area and EEMA ratio in Group C did not reduce significantly(P=0.246). Compared to Group C, MCP-1positive area and EEMA ratio inGroup D was reduced significantly (P=0.04).3The influence of different enantiomer amlodipine on AS model rabbitsartery stenosis (plaque area/lumen area, PA/LA).The PA/LA of four groups are as follows:0.14±0.06，0.07±0.05，0.08±0.05， and0.06±0.04. The datum are Gaussian distribution andhomogeneity. ANOVA shows that the stenosis rate among groups statisticallysignificant (F=4.25, P=0.015). SNK-q multiple comparison shows that, compared with the control, PA/LA of all of drug-therapy groups reducedsignificantly, but there was no statistically significant difference between eachdrug-therapy group.Conclusions：1There is no significant influence between different enantiomeramlodipine on the concentration of serum TC, LDL-C, HDL-C and TG levelof AS model rabbits.2S-amlodipine and racemic amlodipine can significantly reduce theMCP-1positive area and EEMA ratio. Compared to R-amlodipine, racemicamlodipine can significantly reduce the MCP-1positive area and EEMA ratio.3All of different enantiomer amlodipine can significantly preventprocess of AS plaque, decrease AS plaque area and reduce the rate of luminalstenosis. There is no significant difference in reducing the stenosis ratebetween different enantiomer amlodipine.