Changes of κ-opioid receptor in myocardium of rats with ischemia and reperfusion and its relationship with I/R

AIM To investigate the anti-arrhythmic effect of к-opioid receptor (κ-OR) and its changes during myocardial ischemia and reperfusion (I/R). METHODS Forty-eight Sprague- Dawley rats were randomly divided into 6 groups with 8 rats in each group: ①Control group, ②Control+U50,488H group, ③I/R group, ④U50,488H+I/R group, ⑤U50,488H+nor-BNI+I/R group, and ⑥nor-BNI+I/R group. This protocol was used to set up the animal model of myocardial I/R and investigate the effect on ventricular arrhythmic of κ-OR agonist, U50,488H, during I/R. Other Eighteen Sprague-Dawley rats were randomly divided into 6 groups with 3 rats in each group: ①Control group, ②Sham operation group, ③I/R 0 min group, ④I/R 60 min group, ⑤I/R 180 min group, and ⑥I/R 360 min group. This protocol was used to investigate the levels of к-OR mRNA and its protein in rats heart at different time points during I/R by RT-PCR and Western blot, respectively. RESULTS Few ventricular premature contractions were observed in control group and the incidence of arrhythmia in I/R group significantly increased (P<0.01). With pretreatment of U50,488H, the incidence of ventricular tachycardia and ventricular fibrillation (P<0.01) was reduced as well as arrhythmia score in I/R group (P<0.05). With pretreatment of selective κ-OR antagonist (nor-BNI), the anti-arrhythmic effect of U50,488H was completely blocked (P<0.01). But it had no effect on the arrhythmia induced by I/R(P>0.05). Compared with those in control group, the levels of κ-OR mRNA was significantly increased at 0 min, 60 min and 180 min during reperfusion (P<0.01) and increased to utmost amount at 60 min, but decreased to the normal level at 360 min; compared with those in control group, the density of κ-OR protein increased significantly at 0min, 60min, 180min and 360min during reperfusion (P<0.05). CONCLUSION During myocardial I/R, the transcription of κ-OR mRNA and the expression of its protein are increased, which may be related to the anti-arrhythmia effect during myocardial I/R.