title: Is preconditioning by oxytocin administration mediated by iNOS and/or mitochondrial K(ATP) channel activation in the in vivo anesthetized rabbit heart?
abstract: OBJECTIVE
  Oxytocin (OXT) pretreatment protects the heart during ischemia-reperfusion injury by activating ATP-dependent potassium (K(ATP)) channels. The aim of the current study was to elucidate the roles of nitric oxide synthaseNOS and myocardial biochemistry in the cardioprotective effects of OXT and ischemic preconditioning (IPC).
  
  
  METHODS
  Male New Zealand White anesthetized rabbits (13 groups) were subjected to 30 min of occlusion of the left coronary artery and 120 min of reperfusion with or without IPC.
  
  
  RESULTS
  IPC (1 cycle), OXT (0.03 μg/kg, i.p.) or IPC + OXT yield significant infarct size reductions (21.8±1.5%, 20.5±1.2% and 19.4±1.4%, respectively, versus 38.9±3.5% in the S-CONT group; P<0.01) and antiarrhythmic effects, including VF (0%, 0% and 0%, versus 50% in S-CONT group; P<0.05) sustained VT (13%, 13% and 13%, versus 100% in S-CONT group; P<0.005) and other arrhythmias (25%, 13% and 25%, versus 100% in S-CONT group; P<0.005, P<0.01 and P<0.005, respectively). Atosiban (ATO, a selective OXT receptor antagonist), 5-HD and L-NAME (a nonspecific NOS inhibitor) abolished the beneficial effects of IPC and OXT, suggesting that the benefits are achieved via selective activation of OXT receptors, mitochondrial K(ATP) channels and NO. An iNOS inhibitor (1400 W) blocked the beneficial effects of IPC but not OXT. The IPC, OXT, IPC + OXT and 1400 W + OXT interventions significantly preserved ATP levels in the heart.
  
  
  CONCLUSIONS
  This study demonstrates similarities between acute OXT pretreatment and IPC in terms of infarct size reduction, antiarrhythmic activity, and metabolic status.
authors.affiliation: Department of Pharmacology, Sikkim Manipal Institute of Medical Sciences, 5th Mile, Tadong, Gangtok, Sikkim, India. das_biswadeep@hotmail.com
authors.forename: Biswadeep
authors.initials: B
authors.lastname: Das
authors.forename: Chayna
authors.initials: C
authors.lastname: Sarkar
mesh_terms: D000758:Anesthesia; D000818:Animals; D003652:Decanoic Acids / Q000494:pharmacology; D004562:Electrocardiography / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006727:Hormone Antagonists / Q000494:pharmacology; D006880:Hydroxy Acids / Q000494:pharmacology; D019194:Ischemic Preconditioning; D054086:KATP Channels / Q000037:antagonists & inhibitors / Q000502:physiology*; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000502:physiology*; D009203:Myocardial Infarction / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D052247:Nitric Oxide Synthase Type II / Q000502:physiology*; D010121:Oxytocin / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011817:Rabbits; D013534:Survival; D014668:Vasotocin / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D003652:Decanoic Acids; D004791:Enzyme Inhibitors; D006727:Hormone Antagonists; D006880:Hydroxy Acids; D054086:KATP Channels; D026902:Potassium Channel Blockers; C047046:atosiban; D010121:Oxytocin; C052853:5-hydroxydecanoic acid; D052247:Nitric Oxide Synthase Type II; D019331:NG-Nitroarginine Methyl Ester; D014668:Vasotocin