Negative inotropic effect of meperidine in rat ventricular muscle and the underlying mechanism / 生理学报
Acta Physiologica Sinica
; (6): 197-200, 2003.
Article
em Zh
| WPRIM
| ID: wpr-318917
Biblioteca responsável:
WPRO
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.
Texto completo:
1
Índice:
WPRIM
Assunto principal:
Farmacologia
/
Função Ventricular Esquerda
/
Ratos Sprague-Dawley
/
Técnicas de Patch-Clamp
/
Canais de Cálcio Tipo L
/
Miócitos Cardíacos
/
Depressão Química
/
Relação Dose-Resposta a Droga
/
Frequência Cardíaca
/
Meperidina
Limite:
Animals
Idioma:
Zh
Revista:
Acta Physiologica Sinica
Ano de publicação:
2003
Tipo de documento:
Article