title: Endogenous κ-opioid peptide mediates the cardioprotection induced by ischemic postconditioning.
abstract: The aim of this study was to investigate the underlying mechanism that dynorphin, an endogenous kappa opioid receptor (κ-OR) agonist, triggers antiapoptotic effect of postconditioning (Postcon). In addition to vehicle treatment, Sprague Dawley rats (n = 6) underwent a 30-minute left anterior descending occlusion followed by 2 hours of reperfusion with or without a Postcon stimulus. The selective κ-OR antagonist nor-binaltorphimine (Nor-BNI) was administered intravenously 5 minutes before reperfusion. Infarct size was determined by using 2,3,5-triphenyltetrazolium chloride staining. Blood plasma concentrations of creatine kinase (CK) and lactate dehydrogenase (LDH) and myocardial caspase-3 activity were analyzed spectrophotometrically. Myocardial apoptosis was analyzed by the detection of terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick-end labeling. Immunoreactive dynorphin in blood serum and myocardium was measured by means of an antigen-competitive enzyme-linked immunosorbent assay. Infarction size, caspase-3 activity, apoptotic index, and CK and LDH levels were significantly higher in the ischemic/reperfusion group than in the vehicle group (P < 0.01). Postcon significantly reduced infarction size, caspase-3 activity, apoptotic index, CK and LDH levels (P < 0.01 vs. ischemic/reperfusion). Dynorphin content significantly increased after Postcon (P < 0.01). All the effects described above were abolished by Nor-BNI, with the exception of dynorphin content. We found that cardiac protection and antiapoptotic effect of Postcon is mediated by the activation of κ-OR. Effect of Postcon is mediated, at least partially, by enhanced dynorphin expression.
authors.affiliation: Department of Emergency Medicine, Xijing Hospital, Xi'an 710032, China.
authors.forename: Hai-Tao
authors.initials: HT
authors.lastname: Guo
authors.forename: Rong-Huai
authors.initials: RH
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Zhang
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.forename: Quang-Xing
authors.initials: QX
authors.lastname: Shi
authors.forename: Yue-Min
authors.initials: YM
authors.lastname: Wang
authors.forename: Rong
authors.initials: R
authors.lastname: Fan
authors.forename: Hui
authors.initials: H
authors.lastname: Bi
authors.forename: Wen
authors.initials: W
authors.lastname: Yin
authors.forename: Jian-Ming
authors.initials: JM
authors.lastname: Pei
mesh_terms: D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D004399:Dynorphins / Q000097:blood / Q000378:metabolism*; D006439:Hemodynamics; D020287:In Situ Nick-End Labeling; D057775:Ischemic Postconditioning; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000819:agonists*
chemical_list: D017473:Receptors, Opioid, kappa; D004399:Dynorphins