title: Kappa-opioid receptors mediate cardioprotection by remote preconditioning.
abstract: BACKGROUND
  Remote preconditioning is known to be cardioprotective, but the exact mechanism has not been fully elucidated. The objective of the current study was to investigate the role of kappa-opioid receptors in cardioprotection by remote preconditioning and reveal possible underlying mechanisms.
  
  
  METHODS
  Remote preconditioning was induced in anesthetized male Sprague-Dawley rats by three cycles of 5 min of right femoral artery occlusion followed by 5 min of reperfusion. Myocardial ischemia-reperfusion was achieved by ligation of the left anterior descending coronary artery for 30 min and then reperfusion for 120 min. Infarct size was determined by 2,3,5-triphenyltetrazolium chloride staining. Levels of lactate dehydrogenase, dynorphin, and met-enkephalin in plasma were measured. The opening of the mitochondrial permeability transition pore was monitored with fluorescent calcein in isolated ventricular myocytes.
  
  
  RESULTS
  Both remote preconditioning and U-50,488H (10 mg/kg intravenous), a kappa-opioid receptor agonist, significantly decreased the infarct size and plasma lactate dehydrogenase level induced by ischemia-reperfusion, and these effects were attenuated by nor-binaltorphimine (10 mg/kg intravenous), a kappa-opioid receptor antagonist, and atractyloside (5 mg/kg intravenous), a mitochondrial permeability transition pore activator. However, administration of naltrindole (5 mg/kg), a delta-opioid receptor antagonist, had no effect on the cardioprotection by remote preconditioning. The dynorphin plasma level was increased after remote preconditioning treatment, but the met-enkephalin level did not change. In isolated ventricular myocytes loaded with calcein, U-50,488H (300 microM) decreased the mitochondrial permeability transition pore opening induced by calcium (200 microM), and this effect was attenuated by cotreatment with nor-binaltorphimine (5 microM) or atractyloside (20 microM).
  
  
  CONCLUSIONS
  Activation of cardiac kappa-opioid receptors is involved in the cardioprotection induced by remote preconditioning, and the mitochondrial permeability transition pore may participate in the postreceptor pathway.
authors.affiliation: Department of Physiology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Shi-zhong
authors.initials: SZ
authors.lastname: Zhang
authors.forename: Ning-fu
authors.initials: NF
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Xu
authors.forename: Qin
authors.initials: Q
authors.lastname: Gao
authors.forename: Guo-hua
authors.initials: GH
authors.lastname: Lin
authors.forename: Iain C
authors.initials: IC
authors.lastname: Bruce
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xia
mesh_terms: D000818:Animals; D004399:Dynorphins / Q000097:blood; D004744:Enkephalin, Methionine / Q000097:blood; D019157:Ischemic Preconditioning, Myocardial; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D033681:Mitochondrial Membrane Transport Proteins / Q000502:physiology; D000083162:Mitochondrial Permeability Transition Pore; D009203:Myocardial Infarction / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000502:physiology*
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D017473:Receptors, Opioid, kappa; D004744:Enkephalin, Methionine; D004399:Dynorphins; D007770:L-Lactate Dehydrogenase