Effects and mechanisms of U50488H on ventricular arrhythmias induced by myocardial ischemia and reperfusion in rats

Abstract

Abstract: AIM: To investigate the effects and mechanisms of U50488H (a selectiveк-opioid receptor agonist)on ventricular arrhythmias induced by myocardial ischemia and reperfusion in rats.METHODS: Rats were randomly divided into different groups respectively.Heart rate (HR),arterial blood pressure (ABP),left ventricular pressure (LVP),contractive function (+dp/dt_max) and diastolic function (-dp/dt_max) were examined in rats,the incidence of ventricular arrhythmias,arrhythmia score and mechanisms were studied.RESULTS: HR,ABP,LVPand±dp/dt_max in rats were decreased with the administration of U50488H;U50488H intravenously injected before I/R,the incidence of ventricular arrhythmias and arrhythmia score were lowered (P<0.05).The effect of U50488H was abolished in the presence of Nor-BNI,a selectiveк-opioid receptor antagonist.Compared with U50488H +I/R group,with the administration of pertussis toxin,glibenclamide and chelerythrine in advance to block the effects of Gi protein,nitrogen oxide synthase,KATPand PKC respectively,the anti-arrhythmic effects induced byκ-opioid receptor in the rats subjected to myocardial ischemia/reperfusion injures were attenuated (P<0.01).While with the disposal of genistein (5 mg·kg^-1,30 min before U50488H) in advance to block TK,no influence was observed on the anti-arrhythmic effects induced byκ-opioid receptor (P>0.05).CONCLUSIONS: κ-opioid receptor stimulation by U50488H elicits the effects of anti-arrhythmia induced by myocardial ischemia and reperfusion.With the administration of pertussis toxin,glibenclamide and chelerythrine to block Gi/o,PKC and KATPrespectively in advance,the anti-arrhythmic effects mediated byκ-opioid receptor are weakened or completely abolished (P<0.01) which indicates that Gi/o,PKC and K_ATP are signal transduction ways ofκ-opioid receptor activiation.

Key words: к-opioid receptor, myocardial ischemia/reperfusion injury, arrhythmia, Gi protein, protein kinase C, K_ATP channel

CLC Number:

R331.3

References

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