Abstract: Objective To investigate the effect of nociceptin/orphanin FQ (N/OFQ) on ventricular arrhythmias induced by acute myocardial ischemia, and the role of β1-adrenergic receptor (β1-AR) thereof. Methods The rat model of acute myocardial ischemia was prepared by ligating the left anterior descending branch of the coronary artery. A total of 60 rats were randomly divided into 3 groups, namely sham-operation group (Sham group), coronary artery occlusion group (CAO group) and the pretreatment of N/OFQ receptor antagonist (UFP-101) group (U+CAO group). Ten rats were sacrificed at 15 minutes, and another ten rats were sacrificed at 1 hour after CAO. Electrocardiographic data were recorded. The expressions of β1-AR from myocardial cell membrane and whole cell were detected by Western blot assay. The expression of β1-AR mRNA was detected by RT-qPCR. Results Compared with Sham group, ischemic arrhythmias occurred in CAO group, and mainly occurred during 15 minutes after CAO. The pretreatment with UFP-101 can significantly decrease ischemic arrhythmias. At 15 min, compared with Sham group, the expressions of β1-AR and β1-AR mRNA in whole cell were downregulated, and the membrane β1-AR was up-regulated (all P＜0.05) in CAO group. Meanwhile, no significant differences were found in the expression of β1-AR and its mRNA in whole cell (all P＞0.05). The expression of membrane β1-AR was down-regulated (P＜0.05) in U+CAO group. Compared with the CAO group, the expressions of β1-AR and β1-AR mRNA in whole cell were up-regulated while the β1-AR in membrane was down-regulated (all P＜0.05) in U+CAO group. At 1 h,compared with Sham group, the expressions of β1-AR and β1-AR mRNA in the whole cell were up-regulated, and the membrane β1-AR was down-regulated (all P＜0.05) in CAO and U+CAO group. Conclusion Endogenous N/OFQ can regulate the expression of β1-AR in myocardial cell membrane and participate in the process of ischemic arrhythmia in rats.

Key words: arrhythmias, cardiac, myocardial ischemia, receptors, adrenergic, beta-1, nociceptin/orphanin FQ