Amlodipine ameliorates up-regulation of ET-1 in left ventricle of hypercholesterolemia rabbits

ABSTRACT

In addition to antihypertensive effects, amlodipine may exhibit cardiovascular protective effects in heart tissue. The aim of this study was to evaluate the effects of amlodipine and/or high cholesterol diet on blood, heart tissue concentration and mRNA expression of endothelin-1 [ET-1] in male New Zealand white rabbits. A total of 40 male New Zealand rabbits were divided into four groups the normal control groups, normal group receiving amlodipine, high-cholesterol diet group and high-cholesterol diet with amlodipine group. After 8 weeks, all the animals anesthetized and blood or tissues samples were collected. After 8 weeks of a high cholesterol diet, the group with such a diet had a significantly higher ratio of left ventricle [LV] weight to body weight than the control group [P = 0.0001]. After treatment with amlodipine for 8 weeks, ET-1 level was reduced considerably in comparison with the control [P= 0.01] and high-cholesterol diet groups [P= 0.01]. Amlodipine consumption caused significant reduction [P=0.01] in the level of ET-1 in heart tissues of high-cholesterol diet group but it had no remarkable effect on the reduction of heart tissue ET-1 in amlodipine group compared with the control group. The present study demonstrates that ventricular prepro-ET-1 mRNA quantitatively increases in the high-cholesterol diet rabbits which results in development of ventricular hypertrophy. It seems that the treatment with amlodipine retards the progression of LV hypertrophy through attenuation of ET-1 levels independent of lipid changes