[Significance of opioid receptors in regulation of cardiac tolerance in pathogenic impact of long-term ischemia-reperfusion in vivo].
The study aimed at investigation of the role of opioid receptor (OR) in regulation of cardiac tolerance to ischemia-reperfusion. Opioid receptor ligands and inhibitors were administered in vivo prior to coronary artery occlusion (45 min) and reperfusion (2 hrs). Occurring infraction size/area at risk (IS/AAR) ratio was determined. Pretreatment with the micro-OR agonists DAMGO and dermorphin H exerted no effect on the IS/AAR ratio. Activation of delta 1-OR by DPDPE did not alter cardiac tolerance in ischemia-reperfusion either. Pretreatment with the delta 2-OR agonists deltorphin D and deltorphin E or ORL1 receptor agonist nociceptin exerted no effect on the IS/AAR ratio. Stimulation of K-OR by selective agonists did not modify cardiac tolerance to ischemia-reperfusion. The delta 2-OR agonist deltorphin II significantly reduced the IS/AAR index. This effect was prevented by treatment with naltrexone, naloxone methiodide and the delta 2-OR antagonist naltriben but not by the delta 1-OR antagonist BNTX. The infarction-limiting effect of deltorphin II was also abolished by inhibition of protein kinase C (PKC) and mitochondrial Katp channels. Thus, the agonists of micro, delta 1, kappa, and ORL1 receptors in used doses did not affect cardiac tolerance in ischemia-reperfusion injury in vivo. The peripheral delta 2-OR activation induces infarction size reduction. Its infarction-reducing effect of deltorphin II is mediated via PKC activation and mitochondrial Katp, channel opening.
Maslov
L N
LN
Barzakh
E I
EI
Krylatov
A V
AV
Brown
S A
SA
Oeltgen
P R
PR
Govindaswami
M
M
Chernysheva
G A
GA
Solenkova
N V
NV
Lishmanov
A Iu
AIu
Tsibul'nikov
S Iu
SIu
Krieg
T
T
Zhang
E
E
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000187:drug effects; D054086:KATP Channels / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D009292:Narcotic Antagonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000819:agonists / Q000378:metabolism*
D000701:Analgesics, Opioid; D002316:Cardiotonic Agents; D054086:KATP Channels; D009292:Narcotic Antagonists; D011957:Receptors, Opioid