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哌替啶对心室肌收缩的抑制作用及其机制

张雄, 曹春梅, 王琳琳, 丁悦敏, 夏强

浙江大学医学院生理教研室，杭州310031

摘要

为明确哌替啶对心脏收缩的直接效应，并探讨其相关机制。采用La nge ndorff灌流心脏模型，观察了哌替啶对大鼠心室收缩功能的影响，并用荧光测钙技术和膜片钳技术探讨了呱替陡作用的钙离子机制。结果显示，呱替陡剂量依赖性地降低离体灌流心脏的LVDPx HR,+dP/ dt和一dP/ dt，而升高LVEDP。在酶解分离的心室肌细胞上，哌替啶剂量依赖性地降低细胞收缩时的钙瞬变幅度，并升高舒张末期的钙水平。哌替啶不影响高浓度咖啡因诱导的内钙释放。哌替啶使L-型钙电流强度降低到给药前的67. 4士10.1，而不改变钙通道的激活和失活电位。哌替啶减弱钙电流的作用并不能被阿片受体阻断剂纳洛酮所阻断。以上结果表明，哌替啶通过非阿片受体介导的途径阻断细胞外钙离子的内流，对心室收缩产生直接的抑制作用。

关键词： 生理学; 心肌收缩; 膜片钳技术; 哌替啶

Negative isotropic effect of meperidine in rat ventricular muscle and the underlying mechanism

Zhang Xiong, CAO Chun Mei, WANG Lin Lin, DING Yue- Min, Xia Qiang

Department of Physiology，Zhejiang University School of Medicine，Hangzhou

Abstract

The purpose of the present study was to investigate the effect of meperidine on rat ventricular muscle .Cardiac function was assessed in Langendorff-perfused rat hearts and intracellular calcium leve1 was recorded in enzymatically isolated rat ventricular myocytes using spectrofluorometric techniques.To explore the underlying mechanism，whole-cell configuration of patch-clamp technique was used to record L -type Ca~(2+)current .The results showed that meperidine decreased the product of heart rate and left ventricular developed pressure(LVDPx H ，maximal rate of the left ventricular pressure increase (LV+dP/dt,ax) and decrease(LV一d P/ dt wax)，but increased left ventricular end-diastolic pressure in a dose-dependent manner(0一1000 p mol/ L).Meperidine also produced a dose-dependent reduction in electrically induced[Ca~(2+)]，transient amplitude and an increase in diastolic[Ca~(2+)]，baseline level，but did not alter the caffeine(20 m mol/ L) induced Ca~(2+)release from intracellular ryanodine-sensitive Ca~(2+)stores .Meperidine at 100 p mol/ L inhibited L -type Cat十current to 67. 4士10. 1%of control but did not affect the voltage dependency of activation and inactivation .The inhibitory effect of meperidine on Ca~(2+)current could not be prevented by pretreatment with the opioid receptor antagonist naloxone.These data suggest that meperidine exerts a negative inotropic effect by inhibiting L -type Ca~(2+)current .The lack of effect of naloxone implies that the action is independent of the opioid ceptor.

Key words: physiology;myocardial contraction;Patch-clamp techniques;meperidine

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引用本文：

张雄, 曹春梅, 王琳琳, 丁悦敏, 夏强. 哌替啶对心室肌收缩的抑制作用及其机制[J]. 生理学报 2003; 55 (2): .

Zhang Xiong, CAO Chun Mei, WANG Lin Lin, DING Yue- Min, Xia Qiang. Negative isotropic effect of meperidine in rat ventricular muscle and the underlying mechanism. Acta Physiol Sin 2003; 55 (2): (in Chinese with English abstract).