Preserved cardiac mitochondrial function and reduced ischaemia/reperfusion injury afforded by chronic continuous hypoxia: role of opioid receptors.
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.
Laboratory of Experimental Cardiology, Federal State Budgetary Scientific Institution, Research Institute for Cardiology, Tomsk, Russia.
Leonid N
LN
Maslov
Natalia V
NV
Naryzhnaya
Ekaterina S
ES
Prokudina
Frantisek
F
Kolar
Alexander S
AS
Gorbunov
Yi
Y
Zhang
Hongxin
H
Wang
Sergey Yu
SY
Tsibulnikov
Alla G
AG
Portnichenko
Tatiana V
TV
Lasukova
Yury B
YB
Lishmanov
D000222:Adaptation, Physiological; D000818:Animals; D019069:Cell Respiration; D000860:Hypoxia / Q000473:pathology*; D008297:Male; D008929:Mitochondria, Heart / Q000473:pathology*; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000378:metabolism*; D013997:Time Factors
D011957:Receptors, Opioid
cardioprotection; chronic hypoxia; ischaemia/reperfusion; mitochondrial function; opioid receptors