title: Antagonism of endogenous nociceptin/orphanin FQ inhibits infarction-associated ventricular arrhythmias via PKC-dependent mechanism in rats.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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
  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.
authors.affiliation: Department of Anesthesiology, Shanxi Medical University, Second Hospital of Shanxi Medical University, Taiyuan, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Han
authors.forename: Z
authors.initials: Z
authors.lastname: Guo
authors.forename: L L
authors.initials: LL
authors.lastname: Wang
authors.forename: L Z
authors.initials: LZ
authors.lastname: Zhang
authors.forename: T P
authors.initials: TP
authors.lastname: Yao
mesh_terms: D000200:Action Potentials; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000201:enzymology; D009292:Narcotic Antagonists; D018847:Opioid Peptides / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D017180:Tachycardia, Ventricular / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D013997:Time Factors; D018879:Ventricular Premature Complexes / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D000094942:Nociceptin Receptor
chemical_list: D000889:Anti-Arrhythmia Agents; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D011493:Protein Kinase C; D047428:Protein Kinase Inhibitors; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; C479838:(Nphe(1),Arg(14),Lys(15))N-OFQ NH(2); C000722285:Oprl1 protein, rat
keywords: N/OFQ; PKC; action potential duration; acute myocardial infarction; nociceptin/orphanin FQ; ventricular arrhythmia