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 language | English |
|---|---|
| Pages (from-to) | 373-379 |
| Number of pages | 7 |
| Journal | Life Sciences |
| Volume | 93 |
| Issue number | 9-11 |
| DOIs | |
| Publication status | Published - 17 Sep 2013 |
Fingerprint
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 journal › Article
}
TY - JOUR
T1 - Role of endogenous opioid peptides in the infarct size-limiting effect of adaptation to chronic continuous hypoxia
AU - Maslov, Leonid N.
AU - Naryzhnaia, Natalia V.
AU - Tsibulnikov, Sergey Yu
AU - Kolar, Frantisek
AU - Zhang, Yi
AU - Wang, Hongxin
AU - Gusakova, Anna M.
AU - Lishmanov, Yury B.
PY - 2013/9/17
Y1 - 2013/9/17
N2 - 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.
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.
KW - Cardioprotection Opioid peptides
KW - Chronic hypoxia
KW - Myocardial infarction
KW - Opioid receptors
UR - http://www.scopus.com/inward/record.url?scp=84883459014&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84883459014&partnerID=8YFLogxK
U2 - 10.1016/j.lfs.2013.07.018
DO - 10.1016/j.lfs.2013.07.018
M3 - Article
C2 - 23891777
AN - SCOPUS:84883459014
VL - 93
SP - 373
EP - 379
JO - Life Sciences
JF - Life Sciences
SN - 0024-3205
IS - 9-11
ER -