Ranolazine attenuates palmitoyl-L-carnitine-induced mechanical and metabolic derangement in the isolated, perfused rat heart
Ranolazine attenuates palmitoyl-L-carnitine-induced mechanical and metabolic derangement in the isolated, perfused rat heart
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DOI：
10.1211/0022357001774381
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发表时间：
2000-06-01
影响因子：
3.3
通讯作者：
Abiko, Y
中科院分区：
文献类型：
--
作者：
Maruyama, K;Hara, A;Abiko, Y
本文研究了新型抗缺血药物雷诺嗪对棕榈酰-L肉碱所致大鼠心脏机械功能障碍和代谢紊乱的影响，并与丙酮酸脱氢酶激动剂二氯乙酸酯的作用进行了比较。棕榈酰-L-卡尼汀(4mU M)可增加左心室舒张末压，降低左心室发展压(即诱发机械功能障碍)，降低组织三磷酸腺苷水平，增加组织一磷酸腺苷水平(即诱导代谢紊乱)。雷诺嗪(5、10和20 mU M)可浓度依赖性地减弱棕榈酰-L-肉碱引起的上述功能和代谢改变。相反，二氯乙酸酯(1 mM和10 mM)不能减轻棕榈酰-L-肉碱所致的机械和代谢紊乱。然而，在正常(棕榈酰-L-卡尼汀未治疗)心脏中，雷诺嗪并没有改变机械功能和能量代谢。这些结果表明，雷诺嗪可以减轻棕榈酰-L-卡尼汀所致的大鼠心脏的机械和代谢紊乱，雷诺嗪的有益作用不是因为节省能量或激活丙酮酸脱氢酶。
The effect of ranolazine, a novel anti-ischaemic drug that stimulates the activity of pyruvate dehydrogenase, on palmitoyl-L-carnitine-induced mechanical dysfunction and metabolic derangement in isolated perfused rat hearts has been studied and compared with the effect of dichloroacetate, an activator of pyruvate dehydrogenase.Rat hearts paced electrically were perfused aerobically at constant flow by the Langendorff technique. Palmitoyl-L-carnitine (4 mu M) increased left ventricular end-diastolic pressure and reduced left ventricular developed pressure (i.e. induced mechanical dysfunction); it also reduced tissue levels of adenosine triphospbate and increased tissue levels of adenosine monophosphate (i.e. induced metabolic derangement). These functional and metabolic alterations induced by palmitoyl-L-carnitine were attenuated by ranolazine (5, 10, and 20 mu M) in a concentration-dependent manner. In contrast, dichloroacetate (1 and 10mM) did not attenuate palmitoyl-L-carnitine-induced mechanical and metabolic derangement. In the normal (palmitoyl-L-carnitine-untreated) heart, however, ranolazine did not modify mechanical function and energy metabolism.These results suggest that ranolazine attenuates palmitoyl-L-carnitine-induced mechanical and metabolic derangement in the rat heart, and that the beneficial action of ranolazine is not because of the energy-sparing effect or activation of pyruvate dehydrogenase.