Department of Cardiology, The Second Hospital of Shanxi Medical University, No. 382 Wuyi Road, Taiyuan, China.
Arch Med Res. 2011 Jan;42(1):22-7. doi: 10.1016/j.arcmed.2011.01.012.
Amlodipine, a long-acting dihydropyridine calcium channel blocker, is able to improve angiotensin II-mediated vascular endothelial dysfunction. However, the underlying mechanism remains not fully understood. In the present study we attempted to determine whether the protective effect of amlodipine against Ang II-induced endothelial impairment was mediated through blockage of endothelial cell apoptosis.
We pretreated human umbilical venous endothelial cells with increasing doses of amlodipine (10(-8)-10(-6) M) followed by the addition of Ang II. Cell apoptosis was assessed by acridine orange/ethidium bromide staining and by annexin-V/propidium iodide double-labeled cytometry. The involvement of the apoptosis regulators, Bcl-2, Bax, and lectin-like oxidized low-density lipoprotein receptor-1, was determined.
Pretreatment with amlodipine resulted in a dose-dependent suppression of Ang II-induced HUVEC apoptosis. Moreover, the Bcl-2/Bax ratio was found to be increased in cells pretreated with amlodipine, indicating an enhanced anti-apoptosis potential. Additionally, the induction of LOX-1 by Ang II was remarkably counteracted by the pre-exposure to amlodipine.
Our data demonstrate that amlodipine ameliorates Ang II-induced endothelial apoptosis, which is likely associated with the elevation of Bcl-2/Bax ratio and reduction of the LOX-1 expression.
氨氯地平是一种长效二氢吡啶类钙通道阻滞剂，能够改善血管内皮功能障碍。然而，其作用机制尚不完全清楚。本研究旨在确定氨氯地平是否通过抑制内皮细胞凋亡来改善血管紧张素 II（Ang II）诱导的内皮损伤。
用不同浓度的氨氯地平（10(-8)-10(-6) M）预处理人脐静脉内皮细胞，然后加入 Ang II。吖啶橙/溴化乙锭染色和 Annexin-V/碘化丙啶双染流式细胞术评估细胞凋亡。检测凋亡调节因子 Bcl-2、Bax 和凝集素样氧化型低密度脂蛋白受体-1 的作用。
氨氯地平预处理可剂量依赖性抑制 Ang II 诱导的 HUVEC 凋亡。此外，氨氯地平预处理的细胞中 Bcl-2/Bax 比值增加，表明抗凋亡能力增强。此外，Ang II 诱导的 LOX-1 表达明显被氨氯地平预处理所拮抗。
我们的数据表明，氨氯地平改善 Ang II 诱导的内皮细胞凋亡，可能与 Bcl-2/Bax 比值升高和 LOX-1 表达减少有关。
