Role of endogenous opioid peptides in the infarct size-limiting effect of adaptation to chronic continuous hypoxia

Leonid N. Maslov, Natalia V. Naryzhnaia, Sergey Yu Tsibulnikov, Frantisek Kolar, Yi Zhang, Hongxin Wang, Anna M. Gusakova, Yury B. Lishmanov

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Aims 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. Main 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. Key findings 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. Significance 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.

Original languageEnglish
Pages (from-to)373-379
Number of pages7
JournalLife Sciences
Volume93
Issue number9-11
DOIs
Publication statusPublished - 17 Sep 2013

Fingerprint

Opioid Peptides
Opioid Receptors
Rats
Narcotic Antagonists
Reperfusion
Cardiac Arrhythmias
Ischemia
Myocardial Infarction
Endorphins
Plasmas
Methionine Enkephalin
Naltrexone
Peptide Receptors
Coronary Occlusion
Incidence
Opioid Analgesics
Myocardial Ischemia
Coronary Vessels
Animals
Thorax

Keywords

  • Cardioprotection Opioid peptides
  • Chronic hypoxia
  • Myocardial infarction
  • Opioid receptors

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Role of endogenous opioid peptides in the infarct size-limiting effect of adaptation to chronic continuous hypoxia. / Maslov, Leonid N.; Naryzhnaia, Natalia V.; Tsibulnikov, Sergey Yu; Kolar, Frantisek; Zhang, Yi; Wang, Hongxin; Gusakova, Anna M.; Lishmanov, Yury B.

In: Life Sciences, Vol. 93, No. 9-11, 17.09.2013, p. 373-379.

Research output: Contribution to journalArticle

Maslov, LN, Naryzhnaia, NV, Tsibulnikov, SY, Kolar, F, Zhang, Y, Wang, H, Gusakova, AM & Lishmanov, YB 2013, 'Role of endogenous opioid peptides in the infarct size-limiting effect of adaptation to chronic continuous hypoxia', Life Sciences, vol. 93, no. 9-11, pp. 373-379. https://doi.org/10.1016/j.lfs.2013.07.018
Maslov, Leonid N. ; Naryzhnaia, Natalia V. ; Tsibulnikov, Sergey Yu ; Kolar, Frantisek ; Zhang, Yi ; Wang, Hongxin ; Gusakova, Anna M. ; Lishmanov, Yury B. / Role of endogenous opioid peptides in the infarct size-limiting effect of adaptation to chronic continuous hypoxia. In: Life Sciences. 2013 ; Vol. 93, No. 9-11. pp. 373-379.
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AU - Kolar, Frantisek

AU - Zhang, Yi

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AB - Aims 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. Main 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. Key findings 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. Significance 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.

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