Endogenous nociceptin/orphanin FQ affects the occurrence of arrhythmia in acute myocardial ischemia in rats through the regulation of connexin 43 protein

Abstract

Objective Observing influence of various ventricular arrhythmias induced by acute myocardial ischemia and the change of connexin 43 (Cx43) protein content in myocardium in rats and effects of nociceptin/orphanin FQ (OFQ) receptor antagonist UFP-101 on the expression of arrhythmia and Cx43 protein. Methods Sixty-four male SD rats, weighing 200-250 g, were randomly divided into control group(group C, each group was divided into three subgroups, which named coronary artery occlusion 15 min, coronary artery occlusion 60 min and coronary artery occlusion 120 min, n=8), N/OFQ receptor antagonist group (group U, each group was divided into three subgroups, which named coronary artery occlusion 15 min, coronary artery occlusion 60 min and coronary artery occlusion 120 min, n=8), Sham operation group (group S, each group was divided into two subgroups, which named thread without ligation 15 min and thread without ligation 60 min, n=8). Group U was treated with OFQ antagonist compound UFP-101 in the dosage of 1 μl/g by caudal vein. Group C was treated with equal volume of saline. Group C and group U were administered 5 min before they were subjected to the coronary artery occlusion. Group S only was thread without ligation. Record data of electrocardiogram of group C and group U that from 10 min before the injection to 15, 60 min and 120 min after coronary artery occlusion, analyze data of all kinds of ventricular arrhythmia. Determination of expression levels of phosphorylated Cx43 (p-Cx43) protein and total Cx43 protein in all specimens by Western blot. Results At 15 min, numbers of ventricular premature contraction and ventricular bigeminy or trigeminy, the duration of ventricular tachycardia and ventricular fibrillation of group U were obviously lower than numbers in group C (P<0.05). At 60 min, numbers of ventricular premature contraction, ventricular bigeminy and trigeminy, ventricular tachycardia and ventricular fibrillation of group U were lower than those numbers in group C obviously (P<0.05). Expression of p-Cx43 protein at 15 min after coronary artery occlusion, the expression of p-Cx43 in group C were significantly lower than expression levels in group S (P<0.05), the expression of p-Cx43 in group U was significantly higher than that in group C (P<0.05). At 60 min after coronary artery occlusion, the expression of p-Cx43 in group C and group U were significantly lower than expression levels in group S (P<0.05). Conclusions Endogenous OFQ antagonist UFP-101 can reduce the occurrence of arrhythmia in acute myocardial ischemia by promoting phosphorylation of Cx43 protein in rats. Key words: Endogenous nociceptin/orphanin FQ; Protein Cx43; Phosphorylation; Arrhythmia