The Effects Of Different Racemic Amlodipine On Vascular Endothelial Dysfunction Of Rabbits Atherosclerosis Model

Objective: Amlodipine is one of the most extensive usedantihypertensive drug. It is a chiral molecule. Racemic amlodipine arecomposed of S-amlodipine and R-amlodipine in the same size ratio. However,if R-amlodipine has beneficial effects attracted the attention of a large amountof clinician. Even though some scholars deduce R-amlodipine may haveanti-atherosclerotic effects, until now there is only one research shows thatR-amlodipine releases nitric oxide from canine coronary microvessels in vitro.Then going on to deduce that it has the effect of delaying atherosclerosis bystabilizing the normal function of vascular endothelial cells. However, there isno evidence in vivo up to now. To clear and verify this question would beimportant in understanding whether there is an essential difference betweenracemic amlodipine and S-amlodipine on target organs protection. Therefore,we introduced the study on the basis of rabbits atherosclerosis model, to investthe effects of vascular endothelial cells protection and anti-atheroscleroticfunction in different enantiotopic amlodipine.Methods:30male New Zealand rabbits were fed adaptively for1week,and then all the rabbits were randomized allocated in4groups：control group（group A）, S-amlodipine group （group B）, R-amlodipine group （group C） andracemic amlodipine group （group D）. All the rabbits in the4groups were fedon 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） and racemic amlodipine （5mg/d） in the meantime,respectively. Blood samples were collected at baseline,4thweek and8^thweekof rabbits atherosclerosis model after the beginning of the study. The serumconcentration of TC, LDL-C, HDL-C, TG, NO, ET-1, eNOS and iNOS weremeasured separately. All data were shown as x±s, and were undergone normal distribution test and homogeneity test of variance. Comparision among groupswere performed by ANOVA. If it is not conform to Gaussian distribution ofthe data, Kruskal-Wallis test was used. Between groups data were comparedwith SNK-q test. All data analysis was performed by SPSS version13.0（SPSSinc, Chicago, USA）. A p value <0.05was considered statistically significant.Results:1The effects of different enantiotopic amlodipine on TC, LDL-C, HDL-C andTG level in the rabbits serum at baseline1.1Compare with that in the control group, TC level in the drug-therapy groupwas not changed significantly （F＝0.357, P＝0.784）.1.2Compare with that in the control group, LDL-C level in the drug-therapygroup was not changed significantly （F＝0.549, P＝0.654）.1.3Compare with that in the control group, HDL-C level in the drug-therapygroup was not changed significantly （F＝0.562, P＝0.645）.1.4Compare with that in the control group, TG level in the drug-therapygroup was not changed significantly （F＝0.359, P＝0.783）.2The effects of different enantiotopic amlodipine on TC, LDL-C, HDL-C andTG level in the rabbits serum at4thweek2.1Compare with that in the control group, TC level in the drug-therapy groupwas not changed significantly （F＝0.398, P＝0.756）.2.2Compare with that in the control group, LDL-C level in the drug-therapygroup was not changed significantly （F＝1.095, P＝0.370）.2.3Compare with that in the control group, HDL-C level in the drug-therapygroup was not changed significantly （F＝2.501, P＝0.084）.2.4Compare with that in the control group, TG level in the drug-therapygroup was not changed significantly （F＝0.166, P＝0.981）.3The effects of different enantiotopic amlodipine on TC, LDL-C, HDL-C andTG level in the rabbits serum at8^thweek3.1Compare with that in the control group, TC level in the drug-therapy groupwas not changed significantly （F＝0.446, P＝0.722）.3.2Compare with that in the control group, LDL-C level in the drug-therapy group was not changed significantly （F＝1.098, P＝0.369）.3.3Compare with that in the control group, HDL-C level in the drug-therapygroup was not changed significantly （F＝1.733, P＝0.187）.3.4Compare with that in the control group, TG level in the drug-therapygroup was not changed significantly （F＝0.385, P＝0.764）.4The effects of different enantiotopic amlodipine on NO, ET-1, eNOS andiNOS level in the rabbits serum at baseline4.1Compare with that in the control group, NO level in the drug-therapygroup was not changed significantly （P＝0.884）.4.2Compare with that in the control group, ET-1level in the drug-therapygroup was not changed significantly （P＝0.809）.4.3Compare with that in the control group, eNOS level in the drug-therapygroup was not changed significantly （P＝0.774）.4.4Compare with that in the control group, iNOS level in the drug-therapygroup was not changed significantly （P＝0.907）.5The effects of different enantiotopic amlodipine on NO, ET-1, eNOS andiNOS level in the rabbits serum at4thweek5.1Compare with that in the control group, NO in the drug-therapy group wasreduced significantly （P＜0.001）. There was no difference between the B, Cand D group（F=0.105，P=0.901）.5.2Compare with that in the control group, ET-1in the drug-therapy groupwas reduced significantly （P＜0.001）. Compare with that in the B and C group,ET-1in the D group was reduced significantly （P＜0.001）. There was nodifference between the B and C group （F＝0.029, P＝0.868）.5.3Compare with that in the control group, eNOS level in the drug-therapygroup was not changed significantly （F＝0.986, P＝0.416）.5.4Compare with that in the control group, iNOS in the D group was reducedsignificantly （P＜0.001）. There was no significant difference between the A、B, and C group （F＝2.452, P＝0.114）.6The effects of different enantiotopic amlodipine on NO, ET-1, eNOS andiNOS level in the rabbits serum at8^thweek 6.1Compare with that in the control group, NO in the drug-therapy group wasreduced significantly （P＜0.001）. There was no difference between the B, Cand D group （F=0.077, P=0.927）.6.2Compare with that in the control group, ET-1in the drug-therapy groupwas reduced significantly （P＜0.001）. Compare with that in the B and C group,ET-1in the D group was reduced significantly （P＜0.001）. There was nodifference between the B and C group （F＝0.041, P＝0.843）.6.3Compare with that in the control group, eNOS level in the drug-therapygroup was not changed significantly （F＝1.225, P＝0.322）.6.4Compare with that in the control group, iNOS in the D group was reducedsignificantly （P＜0.001）. There was no significant difference between the A、B, and C group （F＝0.613, P＝0.553）.Conclusion:1Different enantiotopic amlodipine did not change the serumconcentration of TC, LDL-C, HDL-C and TG in rabbits atherosclerotic model.2S-amlodipine and R-amlodipine could protect the normal function ofvascular endothelial cells or even having the anti-atherosclerotic effect bydown-regulating the level of ET-1, restraining the expression of iNOS andreducing the production of NO.