Amlodipine treatment decreases plasma and carotid artery tissue levels of endothelin-1 in atherosclerotic rabbits

Alteration in transferring of calcium ions are seen in atherosclerotic cells and amlodipine can positively influence risk factors associated with atherosclerosis, but all mechanisms are not known. Recent studies indicate that endothelin-1 (ET-1) contributes to the atheroma formation and progression of atherosclerosis. In this study, we have evaluated the effects of amlodipine treatment and/or high-cholesterol diet on blood and carotid artery tissue concentration of ET-1 in the atherosclerotic rabbits. Thirty six male New Zealand white rabbits were randomly divided into four groups: normal-diet control (NC), normal-diet receiving amlodipine (NA), high-cholesterol diet (HC) and high-cholesterol diet receiving amlodipine (HA) groups. After 8 weeks all animals were anesthetized and blood or carotid tissue samples were colleted. Eight weeks of amlodipine treatment reduced significantly total cholesterol, LDL and TG in hypercholesterolemic (HA) group. Significant increase in plasma HDL-C and decrease in TG were the main effects of amlodipine treatment on serum lipid profiles in the control group. The plasma and carotid tissue levels of ET-1 in HC group were significantly increased as compared with the NC group (p<0.01). Amlodipine treatment significantly reduced ET-1 level in NA and HA rabbits (p<0.01). Furthermore, high-cholesterol diet induced atherosclerotic lesions as shown by the enhancement of endothelial cell diameter and accumulation of lipid droplets under endothelial cells. Amlodipine treatment reduced atherotic lesions in these rabbits. Amlodipine treatment reduced levels of total cholesterol, LDL and TG as well as plasma and carotid tissue levels of ET-1 in high lipid situation. We suggest that amlodipine treatment by reducing the ET-1 may contribute to reducing the progression of atherosclerotic disease.