Abstract
Chronic continuous normobaric hypoxia (CNH) increases cardiac tolerance to acute ischaemia/reperfusion injury. The objective of this study was to find out whether the cardioprotective effect of CNH mediated by opioid receptors is associated with preservation of mitochondrial function. Rats were adapted to CNH (12% oxygen) for 3 weeks. Isolated perfused hearts were subjected to 45 min of global ischaemia and 30 min of reperfusion; subgroups were pretreated with non-selective opioid receptor antagonist naloxone (300 nmol/L) for 10 min. Cardiac contractile function, creatine kinase activity in coronary effluent, mitochondrial respiration rate, and calcium retention capacity were assessed. Adaptation to CNH decreased myocardial creatine kinase release during reperfusion and improved the post-ischaemic recovery of contractile function, mitochondrial state 3 and uncoupled respiration rates, and calcium retention capacity compared to the normoxic group. These protective effects were completely abolished by naloxone. The contractile recovery positively correlated with state 3 respiration and calcium retention capacity. The results suggest that the preserved mitochondrial function contributes to the protected cardiac phenotype afforded by adaptation to CNH and point to an important role of opioid receptor activation.
| Original language | English |
|---|---|
| Pages (from-to) | 496-501 |
| Number of pages | 6 |
| Journal | Clinical and Experimental Pharmacology and Physiology |
| Volume | 42 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 1 May 2015 |
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Keywords
- Cardioprotection
- Chronic hypoxia
- Ischaemia/reperfusion
- Mitochondrial function
- Opioid receptors
ASJC Scopus subject areas
- Physiology
- Physiology (medical)
- Pharmacology
Cite this
Preserved cardiac mitochondrial function and reduced ischaemia/reperfusion injury afforded by chronic continuous hypoxia : Role of opioid receptors. / Maslov, Leonid N.; Naryzhnaya, Natalia V.; Prokudina, Ekaterina S.; Kolar, Frantisek; Gorbunov, Alexander S.; Zhang, Yi; Wang, Hongxin; Tsibulnikov, Sergey Yu; Portnichenko, Alla G.; Lasukova, Tatiana V.; Lishmanov, Yury B.
In: Clinical and Experimental Pharmacology and Physiology, Vol. 42, No. 5, 01.05.2015, p. 496-501.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Preserved cardiac mitochondrial function and reduced ischaemia/reperfusion injury afforded by chronic continuous hypoxia
T2 - Role of opioid receptors
AU - Maslov, Leonid N.
AU - Naryzhnaya, Natalia V.
AU - Prokudina, Ekaterina S.
AU - Kolar, Frantisek
AU - Gorbunov, Alexander S.
AU - Zhang, Yi
AU - Wang, Hongxin
AU - Tsibulnikov, Sergey Yu
AU - Portnichenko, Alla G.
AU - Lasukova, Tatiana V.
AU - Lishmanov, Yury B.
PY - 2015/5/1
Y1 - 2015/5/1
N2 - Chronic continuous normobaric hypoxia (CNH) increases cardiac tolerance to acute ischaemia/reperfusion injury. The objective of this study was to find out whether the cardioprotective effect of CNH mediated by opioid receptors is associated with preservation of mitochondrial function. Rats were adapted to CNH (12% oxygen) for 3 weeks. Isolated perfused hearts were subjected to 45 min of global ischaemia and 30 min of reperfusion; subgroups were pretreated with non-selective opioid receptor antagonist naloxone (300 nmol/L) for 10 min. Cardiac contractile function, creatine kinase activity in coronary effluent, mitochondrial respiration rate, and calcium retention capacity were assessed. Adaptation to CNH decreased myocardial creatine kinase release during reperfusion and improved the post-ischaemic recovery of contractile function, mitochondrial state 3 and uncoupled respiration rates, and calcium retention capacity compared to the normoxic group. These protective effects were completely abolished by naloxone. The contractile recovery positively correlated with state 3 respiration and calcium retention capacity. The results suggest that the preserved mitochondrial function contributes to the protected cardiac phenotype afforded by adaptation to CNH and point to an important role of opioid receptor activation.
AB - Chronic continuous normobaric hypoxia (CNH) increases cardiac tolerance to acute ischaemia/reperfusion injury. The objective of this study was to find out whether the cardioprotective effect of CNH mediated by opioid receptors is associated with preservation of mitochondrial function. Rats were adapted to CNH (12% oxygen) for 3 weeks. Isolated perfused hearts were subjected to 45 min of global ischaemia and 30 min of reperfusion; subgroups were pretreated with non-selective opioid receptor antagonist naloxone (300 nmol/L) for 10 min. Cardiac contractile function, creatine kinase activity in coronary effluent, mitochondrial respiration rate, and calcium retention capacity were assessed. Adaptation to CNH decreased myocardial creatine kinase release during reperfusion and improved the post-ischaemic recovery of contractile function, mitochondrial state 3 and uncoupled respiration rates, and calcium retention capacity compared to the normoxic group. These protective effects were completely abolished by naloxone. The contractile recovery positively correlated with state 3 respiration and calcium retention capacity. The results suggest that the preserved mitochondrial function contributes to the protected cardiac phenotype afforded by adaptation to CNH and point to an important role of opioid receptor activation.
KW - Cardioprotection
KW - Chronic hypoxia
KW - Ischaemia/reperfusion
KW - Mitochondrial function
KW - Opioid receptors
UR - http://www.scopus.com/inward/record.url?scp=84928194200&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84928194200&partnerID=8YFLogxK
U2 - 10.1111/1440-1681.12383
DO - 10.1111/1440-1681.12383
M3 - Article
C2 - 25739423
AN - SCOPUS:84928194200
VL - 42
SP - 496
EP - 501
JO - Clinical and Experimental Pharmacology and Physiology
JF - Clinical and Experimental Pharmacology and Physiology
SN - 0305-1870
IS - 5
ER -