Department of Cardiology, Nagoya University Graduate School of Medicine, Japan.
Am J Hypertens. 2012 Apr;25(4):401-6. doi: 10.1038/ajh.2011.239. Epub 2012 Jan 5.
Obesity is a risk factor for the development of cardiovascular diseases that are associated with impaired angiogenesis. Nifedipine, a calcium-channel blocker, has a number of blood pressure (BP)-independent effects as well, such as improving endothelial function and decreasing oxidative stress. Here, we investigated whether nifedipine could improve the angiogenic responses in a diet-induced obese (DIO) model.
DIO was induced by allowing 8-week-old C57BL/6J mice ad libitum access to a high-fat/high-sucrose (HF/HS) diet. Mice were randomly divided into two groups that were fed either the HF/HS or normal chow. At the age of 12 weeks, the animals were treated/not treated with nifedipine admixed with food at a concentration of 0.001%. Then, 1 week later, the mice were subjected to unilateral hind limb surgery.
Angiogenic repair of the ischemic hind limb was impaired in the DIO mice as compared with that in the control mice as evaluated by laser Doppler blood flowmetry (LDBF) and capillary density analysis. Treatment with nifedipine accelerated angiogenic repair in the DIO mice to a level equal to that seen in the control mice. DIO mice showed increased reactive oxygen species (ROS) production after hind limb ischemia. The number of endothelial progenitor cells (EPCs), which contribute to blood vessel formation, was also significantly lower in these mice. Nifedipine treatment ameliorated the oxidative status and increased the number of EPCs in the DIO mice.
Our observations demonstrated that DIO impaired revascularization in response to tissue ischemia. Nifedipine ameliorated obesity-impaired revascularization through suppressing oxidative stress and enhancing the number of EPCs.
肥胖是心血管疾病发展的一个风险因素，而心血管疾病与血管生成受损有关。硝苯地平是一种钙通道阻滞剂，除了具有降血压作用外，还有改善内皮功能和减少氧化应激等多种非降压作用。在此，我们研究了硝苯地平是否能改善饮食诱导肥胖（DIO）模型中的血管生成反应。
通过允许 8 周龄 C57BL/6J 小鼠随意摄入高脂肪/高蔗糖（HF/HS）饮食来诱导 DIO。将小鼠随机分为两组，一组喂食 HF/HS，另一组喂食正常饲料。在 12 周龄时，将动物用与食物混合的硝苯地平（浓度为 0.001%）进行处理/不处理。1 周后，对小鼠进行单侧后肢手术。
与对照组相比，DIO 小鼠的缺血后肢的血管生成修复受损，通过激光多普勒血流测量（LDBF）和毛细血管密度分析进行评估。硝苯地平治疗加速了 DIO 小鼠的血管生成修复，使其达到与对照组相同的水平。DIO 小鼠在下肢缺血后产生的活性氧（ROS）增加。这些小鼠的内皮祖细胞（EPCs）数量也明显减少，EPCs 有助于血管形成。硝苯地平治疗改善了 DIO 小鼠的氧化状态并增加了 EPCs 的数量。
我们的观察结果表明，DIO 损害了组织缺血后的再血管化。硝苯地平通过抑制氧化应激和增加 EPCs 的数量来改善肥胖引起的再血管化受损。
