生理学报Acta Physiologica Sinica, April

研究论文

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Langendorff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哌替啶作用的钙离子机制。结果显示, 哌替啶剂量依赖性地降低离体灌流心脏的LVDP×HR、 +dP/dt和-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±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, 哌替啶能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

中图分类号: Q463

Negative inotropic 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 310031

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 level 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 Ca2+ current. The results showed that meperidine decreased the product of heart rate and left ventricular developed pressure (LVDP×HR), maximal rate of the left ventricular pressure increase (LV +dP/dtmax) and decrease (LV -dP/dtmax), but increased left ventricular end-diastolic pressure in a dose-dependent manner (0-1000 μmol/L). Meperidine also produced a dose-dependent reduction in electrically induced [Ca2+]i transient amplitude and an increase in diastolic [Ca2+]i baseline level, but did not alter the caffeine (20 mmol/L) induced Ca2+ release from intracellular ryanodine-sensitive Ca2+ stores. Meperidine at 100 μmol/L inhibited L-type Ca2+ current to 67.4±10.1% of control but did not affect the voltage dependency of activation and inactivation. The inhibitory effect of meperidine on Ca2+ 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 Ca2+ current. The lack of effect of naloxone implies that the action is independent of the opioid receptor.

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