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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Citing This Article:
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).