[Negative inotropic effect of meperidine in rat ventricular muscle and the underlying mechanism].
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.
Zhang
Xiong
X
Department of Physiology, Zhejiang University School of Medicine, Hangzhou, PR China.
Cao
Chun-Mei
CM
Wang
Lin-Lin
LL
Ding
Yue-Min
YM
Xia
Qiang
Q
D000818:Animals; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008614:Meperidine / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D016277:Ventricular Function, Left / Q000187:drug effects*
D020746:Calcium Channels, L-Type; D008614:Meperidine