title: Role of endogenous opioid peptides in the infarct size-limiting effect of adaptation to chronic continuous hypoxia.
abstract: OBJECTIVE
  The objective of this study was to examine the involvement of endogenous opioid peptides and opioid receptor (OR) subtypes in the cardioprotective effect of adaptation to chronic hypoxia in rats.
  
  
  METHODS
  Rats were exposed to continuous normobaric hypoxia (CNH; 12% oxygen) for 3 weeks. Myocardial ischemia was induced by 20-min coronary artery occlusion followed by 3-h reperfusion in anesthetized open-chest animals. Various OR antagonists were administered to rats prior to ischemia. The size of myocardial infarction and the incidence of ischemic ventricular arrhythmias were assessed. Myocardial and plasma concentrations of opioid peptides (met-enkephalin, β-endorphin, and endomorphins) were determined.
  
  
  RESULTS
  Adaptation to CNH significantly increased myocardial and plasma concentrations of opioids, potentiated their further elevation by ischemia/reperfusion, and reduced myocardial infarct size, but it did not affect the incidence of ischemic arrhythmias. The infarct size-limiting effect of CNH was abolished by OR antagonists naltrexone (non-selective), naloxone methiodide (non-selective peripherally acting), TIPP[ψ] (δ-OR), naltriben (δ2-OR), or CTAP (μ-OR), while BNTX (δ1-OR) and nor-binaltorphimine (κ-OR) had no effect.
  
  
  CONCLUSIONS
  The results suggest that the infarct size-limiting effect afforded by adaptation to CNH is mediated by activation of peripheral δ2- and μ-ORs by elevated levels of endogenous opioid peptides.
authors.affiliation: Laboratory Experimental Cardiology, Research Institute for Cardiology, Siberian Branch of the Russian Academy of Medical Sciences, Tomsk 634012, Russia. maslov@cardio.tsu.ru
authors.forename: Leonid N
authors.initials: LN
authors.lastname: Maslov
authors.forename: Natalia V
authors.initials: NV
authors.lastname: Naryzhnaia
authors.forename: Sergey Yu
authors.initials: SY
authors.lastname: Tsibulnikov
authors.forename: Frantisek
authors.initials: F
authors.lastname: Kolar
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hongxin
authors.initials: H
authors.lastname: Wang
authors.forename: Anna M
authors.initials: AM
authors.lastname: Gusakova
authors.forename: Yury B
authors.initials: YB
authors.lastname: Lishmanov
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology*; D004744:Enkephalin, Methionine / Q000378:metabolism; D000860:Hypoxia / Q000150:complications; D008297:Male; D009203:Myocardial Infarction / Q000209:etiology / Q000503:physiopathology*; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D009292:Narcotic Antagonists / Q000494:pharmacology; D009842:Oligopeptides / Q000097:blood / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017465:Receptors, Opioid, delta / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000378:metabolism; D001615:beta-Endorphin / Q000378:metabolism
chemical_list: D009292:Narcotic Antagonists; D009842:Oligopeptides; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; C105293:endomorphin 1; C105294:endomorphin 2; D004744:Enkephalin, Methionine; D001615:beta-Endorphin
keywords: Cardioprotection; Chronic hypoxia; Myocardial infarction; Opioid peptides; Opioid receptors