Nicardipine prevents calcium loading and "oxygen paradox" in anoxic single rat myocytes by a mechanism independent of calcium channel blockade.
Nicardipine prevents calcium loading and "oxygen paradox" in anoxic single rat myocytes by a mechanism independent of calcium channel blockade.
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尼卡地平通过独立于钙通道阻断的机制防止缺氧单只大鼠肌细胞中的钙负荷和“氧悖论”。
DOI：
10.1161/01.res.69.6.1500
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发表时间：
1991
影响因子：
20.1
通讯作者：
Stern,MD
中科院分区：
文献类型：
--
作者：
Hano,O;Silverman,HS;Blank,PS;Mellits,ED;Baumgardner,R;Lakatta,EG;Stern,MD
尼卡地平（1和4 μ M）对复氧损伤的保护作用进行了研究，在一个未受刺激的大鼠单心肌细胞氧悖论模型与对照（无药物）或硝苯地平（1 μ M）。任一浓度的尼卡地平都具有强烈的保护作用，使细胞在再氧合时能够承受的ATP耗竭（僵直）持续时间大约增加一倍，而不会发生过度挛缩。硝苯地平（1 μ M）与尼卡地平（4 μ M）的负性肌力作用（通过刺激时缩短的程度测量）相匹配，对复氧损伤没有保护作用。这两种药物都不影响僵直时间，僵直时间是静息细胞在无氧代谢期间消耗其内源性糖原储存的速率的量度。用荧光探针indo-1测量的细胞内钙（分配到胞质溶胶和线粒体中）在整个僵硬期间逐渐升高。尼卡地平（1 μ M）几乎完全抑制了钙的升高，但硝苯地平不影响钙的升高。我们得出结论，尼卡地平具有直接的心肌保护作用，而不是所有的二氢吡啶。这种作用与防止细胞内（可能是线粒体）钙负荷有关，但可能不是由于阻断L型钙通道或降低代谢率。
The protective effect of nicardipine (1 and 4 microM) against reoxygenation injury was studied in an unstimulated rat single myocyte oxygen paradox model in comparison with control (no drug) or nifedipine (1 microM). Either concentration of nicardipine was strongly protective, approximately doubling the duration of ATP depletion (rigor) that cells could withstand without undergoing hypercontracture when reoxygenated. Nifedipine (1 microM), which matched the negative inotropic effect of nicardipine (4 microM) (as measured by extent of shortening when stimulated), had no protective effect against reoxygenation injury. Neither drug affected the time to rigor, which is a measure of the rate at which the resting cell consumes its endogenous glycogen stores during anaerobic metabolism. Intracellular calcium, measured with the fluorescent probe indo-1, which partitions into both cytosol and mitochondria, rose progressively throughout the rigor period. This rise in calcium was almost totally suppressed by nicardipine (1 microM) but was unaffected by nifedipine. We conclude that nicardipine possesses a direct protective effect on the myocardium not shared by all dihydropyridines. This effect is associated with the prevention of intracellular, and probably mitochondrial, calcium loading but is probably not due to blockade of the L-type calcium channel or reduction of metabolic rate.