Y Han1, Z Guo, L L Wang, L Z Zhang, T P Yao. 1. Department of Anesthesiology, Shanxi Medical University, Second Hospital of Shanxi Medical University, Taiyuan, China.
Abstract
BACKGROUND AND PURPOSE: Evidence indicates nociceptin/orphanin FQ (N/OFQ) may participate in the pathology of cardiac arrhythmias associated with myocardial infarction. But the role of N/OFQ in the arrhythmogenesis in acute myocardial infarction is unclear. The aim of this study was to investigate the effects of endogenous N/OFQ on infarction-associated arrhythmias. EXPERIMENTAL APPROACH: The expression of N/OFQ, PKC activity and ventricular arrhythmias in presence and absence of UFP-101, a specific antagonist of N/OFQ receptor, were examined following permanent coronary artery occlusion in anaesthetized rats. The effect of N/OFQ on action potential duration was examined in isolated rat cardiomyocytes. KEY RESULTS: It was observed that N/OFQ was increased by 41% in the myocardium after coronary artery occlusion (P < 0.01 vs. control). Pretreatment with UFP-101 (10(-7) mol·kg(-1) , i.v.) reduced the incidence of ventricular ectopic beats by 70% and ventricular tachycardia by 51% respectively (all P < 0.05 vs. control). Meanwhile, PKC activity was elevated in the rats treated with UFP-101 (by 35%, P < 0.05 vs. control). A selective PKC inhibitor, calphostin C, completely abolished the anti-arrhythmic effects of UFP-101 (P < 0.01). N/OFQ (at 10(-11) , 10(-9) and 1 × 10(-7) mol·L(-1) ) shortened the action potential duration by 3% (P > 0.05), 10% (P < 0.05) and 22% (P < 0.01), respectively, via N/OFQ receptor. CONCLUSIONS AND IMPLICATIONS: Antagonism of endogenous N/OFQ produces anti-arrhythmic effects on ventricular arrhythmias in acute myocardial infarction, possibly via modulating PKC activity and action potential of myocytes.
BACKGROUND AND PURPOSE: Evidence indicates nociceptin/orphanin FQ (N/OFQ) may participate in the pathology of cardiac arrhythmias associated with myocardial infarction. But the role of N/OFQ in the arrhythmogenesis in acute myocardial infarction is unclear. The aim of this study was to investigate the effects of endogenous N/OFQ on infarction-associated arrhythmias. EXPERIMENTAL APPROACH: The expression of N/OFQ, PKC activity and ventricular arrhythmias in presence and absence of UFP-101, a specific antagonist of N/OFQ receptor, were examined following permanent coronary artery occlusion in anaesthetized rats. The effect of N/OFQ on action potential duration was examined in isolated rat cardiomyocytes. KEY RESULTS: It was observed that N/OFQ was increased by 41% in the myocardium after coronary artery occlusion (P < 0.01 vs. control). Pretreatment with UFP-101 (10(-7) mol·kg(-1) , i.v.) reduced the incidence of ventricular ectopic beats by 70% and ventricular tachycardia by 51% respectively (all P < 0.05 vs. control). Meanwhile, PKC activity was elevated in the rats treated with UFP-101 (by 35%, P < 0.05 vs. control). A selective PKC inhibitor, calphostin C, completely abolished the anti-arrhythmic effects of UFP-101 (P < 0.01). N/OFQ (at 10(-11) , 10(-9) and 1 × 10(-7) mol·L(-1) ) shortened the action potential duration by 3% (P > 0.05), 10% (P < 0.05) and 22% (P < 0.01), respectively, via N/OFQ receptor. CONCLUSIONS AND IMPLICATIONS: Antagonism of endogenous N/OFQ produces anti-arrhythmic effects on ventricular arrhythmias in acute myocardial infarction, possibly via modulating PKC activity and action potential of myocytes.
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