Department of Pharmacology, Faculty of Pharmacy, Ege University, İzmir, Turkey.
Vascul Pharmacol. 2010 Nov-Dec;53(5-6):193-9. doi: 10.1016/j.vph.2010.08.003. Epub 2010 Aug 12.
The antiatherosclerotic effect of lacidipine has been attributed to its actions on cholesterol levels, lipid metabolism or oxidant stress in advanced disease. The purpose of the present experiments was to examine whether lacidipine is protective of intimal thickening and vascular dysfunction in early atherosclerosis in the absence of the hypertension and hypercholesterolemia. A second goal was to determine whether and to what extent MMP-9 and oxidant stress are involved in possible beneficial effects of lacidipine. Lacidipine treatment (5 mg/kg/day, p.o. for 3 weeks) significantly prevented the collar-induced intimal thickening. MMP-9 expressions were increased by collar but not effected by lacidipine treatment. Nitrotyrosine staining, a marker for oxidant stress was not changed neither by collar nor lacidipine treatment in early atherosclerosis. The enhanced sensitivity to serotonine and diminished sensitivity to acetylcholine in collared arteries were restored to normal levels with treatment. These results demonstrate that the lacidipine treatment prevents the collar-induced intimal thickening and accompanying vascular dysfunction in early atherosclerosis without cholesterol loading. These beneficial effects of lacidipine were not associated with changes in either MMP-9 expression or oxidant stress. However, enhanced endothelium-dependent relaxations by lacidipine, suggest that vascular protective effects of nitric oxide may be at least partly, responsible from antiatherosclerotic effects of lacidipine.
拉西地平的抗动脉粥样硬化作用归因于其对胆固醇水平、脂质代谢或氧化应激的作用在晚期疾病中。本实验的目的是研究在没有高血压和高胆固醇血症的情况下,拉西地平是否对早期动脉粥样硬化的内膜增厚和血管功能障碍具有保护作用。第二个目标是确定 MMP-9 和氧化应激是否参与了拉西地平的可能有益作用,并确定其参与的程度。拉西地平治疗(5mg/kg/天,口服,持续 3 周)显著预防了套环引起的内膜增厚。MMP-9 的表达被套环增加,但不受拉西地平治疗的影响。在早期动脉粥样硬化中,硝基酪氨酸染色(氧化应激的标志物)既不受套环也不受拉西地平治疗的影响。用拉西地平治疗后,套环动脉中对 5-羟色胺的敏感性增加和对乙酰胆碱的敏感性降低恢复正常。这些结果表明,拉西地平治疗可预防早期动脉粥样硬化中套环引起的内膜增厚和伴随的血管功能障碍,而无需胆固醇负荷。拉西地平的这些有益作用与 MMP-9 表达或氧化应激的变化无关。然而,拉西地平增强了内皮依赖性松弛,提示一氧化氮的血管保护作用可能至少部分负责拉西地平的抗动脉粥样硬化作用。