Amlodipine and carvedilol prevent cytotoxicity in cortical neurons isolated from stroke-prone spontaneously hypertensive rats.
Amlodipine and carvedilol prevent cytotoxicity in cortical neurons isolated from stroke-prone spontaneously hypertensive rats.
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DOI：
10.1291/hypres.27.271
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发表时间：
2004-04
期刊：
影响因子：
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通讯作者：
K. Yamagata;S. Ichinose;M. Tagami
中科院分区：
文献类型：
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作者：
K. Yamagata;S. Ichinose;M. Tagami
我们之前报道过维生素E可以防止脑缺血和再灌注时自发性高血压大鼠（SHRSP）神经元的凋亡。在本文中，我们分析了在缺氧（1% O2）后再充氧（20% O2）后添加抗高血压药和维生素E的效果。在缺氧后再加维生素E，对神经元细胞具有显著的保护作用。研究还表明，在缺氧和再氧之前，维生素E可以完全保护神经细胞免于死亡。在较高浓度的维生素E中，观察到较强的神经保护作用。此外，我们验证了氨氯地平、卡维地洛或双嘧达莫预处理均可防止缺氧和再氧化（H/R）期间的细胞死亡。另一方面，二氢吡啶型钙进入阻滞剂尼伐地平在H/R期间没有明显的神经保护作用。神经保护作用强弱顺序为：维生素E >双嘧达莫>卡维地洛>或=氨氯地平>尼伐地平。在平行实验中，我们检查了这些抗高血压药物与维生素E和双嘧达莫联合使用是否更有效。结果表明，在体外模型系统中，抗氧化剂是减少皮层神经元氧自由基损伤的最重要的药物。这些结果表明，氨氯地平和卡维地洛具有抗氧化和降压活性，可能有助于抑制高血压患者脑血管卒中和神经退行性疾病的神经元细胞死亡。
We previously reported that vitamin E prevents apoptosis in neurons during cerebral ischemia and reperfusion in stroke-prone spontaneously hypertensive rats (SHRSP). In this paper, we analyzed the effects of antihypertensives as well as vitamin E, which were added to neuron cultures after reoxygenation (20% O2) following hypoxia (1% O2). When added after hypoxia before reoxygenation, vitamin E conferred significant protection to neuronal cells. It was also shown that vitamin E conferred complete protection from neural cell death when added hypoxia and again before reoxygenation. At higher concentrations of vitamin E, strong neuroprotection was observed. Moreover, we verified that pretreatment with either amlodipine, carvedilol or dipyridamole consistently prevented cell death during hypoxia and reoxygenation (H/R). On the other hand, nilvadipine, a dihydropyridine-type calcium entry blocker, had no apparent effect on neuroprotection during H/R. The order of neuroprotective potency was vitamin E > dipyridamole > carvedilol > or = amlodipine > nilvadipine. In parallel experiments, we examined whether these antihypertensive agents were more effective when combined with vitamin E and dipyridamole. The results suggested that in our in vitro model system, antioxidants were the most important agents for the reduction of oxygen-free radical damage in cortical neurons. These findings suggest that amlodipine and carvedilol, with their antioxidant properties and antihypertensive activity, would be useful to inhibit neuronal cell death in the treatment of cerebrovascular stroke and neurodegenerative diseases in hypertensive patients.