Protective effect of benidipine against sodium azide-induced cell death in cultured neonatal rat cardiac myocytes
Protective effect of benidipine against sodium azide-induced cell death in cultured neonatal rat cardiac myocytes
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DOI：
10.1254/jphs.93.163
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发表时间：
2003-10-01
影响因子：
3.5
通讯作者：
Tanaka, H
中科院分区：
文献类型：
--
作者：
Inomata, K;Tanaka, H
我们研究了贝尼地平，一种钙拮抗剂，对叠氮化钠（NaN 3）诱导的培养的新生大鼠心肌细胞的LDH释放增加，细胞ATP含量的耗竭，线粒体膜电位（AT）的崩溃为指标的细胞死亡的影响。用1 mmol/L NaN 3处理细胞18 h。贝尼地平浓度依赖性地抑制NaN 3诱导的细胞死亡。将贝尼地平的保护作用与曲马多、硝苯地平、坎地沙坦和卡托普利进行比较。钙拮抗剂表现出保护作用，贝尼地平、利多卡因和硝苯地平的IC 50值分别为0.65、90和65 nmol/L。NaN 3诱导的细胞死亡被钙蛋白酶抑制剂完全抑制。有人认为，持续升高的[Ca ~（2+）]（i）可能与NaN_3诱导的细胞死亡有关。贝尼地平，而且，浓度依赖性地保存细胞ATP含量和维持Deltapsi的程度的控制水平。总之，贝尼地平在NaN 3诱导的心脏细胞死亡模型中显示出比硝苯地平和硝苯地平低约100倍的保护作用。贝尼地平的保护作用可能与抑制Ca ~（2+）内流和保护细胞ATP含量有关。
We investigated the effect of benidipine, a calcium antagonist, against sodium azide (NaN3)-induced cell death in cultured neonatal rat cardiac myocytes with increase of LDH release, depletion of cellular ATP contents, and collapse of mitochondrial membrane potential (AT) as indicators. Cells were treated with 1 mmol/L NaN3 for 18 h. Benidipine concentration-dependently inhibited NaN3-induced cell death. The protective effect of benidipine was compared with those of amlodipine, nifedipine, candesartan, and captopril. Calcium antagonists exhibited a protective effect and the IC50 values of benidipine, amlodipine, and nifedipine were 0.65, 90, and 65 nmol/L, respectively. NaN3-induced cell death was inhibited completely with the calpain inhibitor. It was considered that the sustained elevation of [Ca2+](i) might be implicated in NaN3-induced cell death. Benidipine, moreover, concentration-dependently preserved cellular ATP contents and maintained Deltapsi the extent of the control level. In conclusion, benidipine exhibited the protective effect at an approximately 100-fold lower concentration than those of amlodipine and nifedipine in the NaN3-induced cardiac cell death model. It was considered that both the inhibition of Ca2+ influx and the preservation of cellular ATP contents might play an important role in the protective effect of benidipine.