Negative inotropic effect of meperidine in rat ventricular muscle and the underlying mechanism.
- Author:
Xiong ZHANG
1
;
Chun-Mei CAO
;
Lin-Lin WANG
;
Yue-Min DING
;
Qiang XIA
Author Information
1. Department of Physiology, Zhejiang University School of Medicine, Hangzhou, PR China.
- Publication Type:Journal Article
- MeSH:
Animals;
Calcium Channels, L-Type;
drug effects;
Depression, Chemical;
Dose-Response Relationship, Drug;
Heart Rate;
drug effects;
Male;
Meperidine;
pharmacology;
Myocardial Contraction;
drug effects;
Myocytes, Cardiac;
metabolism;
Patch-Clamp Techniques;
Rats;
Rats, Sprague-Dawley;
Ventricular Function, Left;
drug effects
- From:
Acta Physiologica Sinica
2003;55(2):197-200
- CountryChina
- Language:Chinese
-
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 Ca(2+) 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/dt(max)) and decrease (LV -dP/dt(max)), but increased left ventricular end-diastolic pressure in a dose-dependent manner (0-1000 micromol/L). Meperidine also produced a dose-dependent reduction in electrically induced [Ca(2+)](i) transient amplitude and an increase in diastolic [Ca(2+)](i) baseline level, but did not alter the caffeine (20 mmol/L) induced Ca(2+) release from intracellular ryanodine-sensitive Ca(2+) stores. Meperidine at 100 micromol/L inhibited L-type Ca(2+) 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 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 receptor.
