Stimulation of mu and delta-Opiate Receptors and Tolerance of Isolated Heart to Oxidative Stress: the Role of NO-Synthase.
Preliminary intravenous injection of delta-opiate receptor (OR) agonists DSLET (0.1 mg/kg) or DTLET (0.1 mg/kg) increased tolerance of isolated perfused myocardium to damage by oxidative stress simulated in vivo with FeSO4 + ascorbic acid. This manifested itself by a decreased level of creatine phosphokinase (CPK) in the perfusate flowing out of the heart during the oxidative exposure. The preliminary systemic injection of mu-agonists DAMGO (0.1 mg/kg) or DALDA (0.1 mg/kg) failed to affect the release of CPK from the myocardium. The cardioprotective effect of the delta-agonist DSLET was completely abolished by preliminary intravenous injection of the delta-OR antagonist ICI 174,864 (2.5 mg/kg). The intravenous injection of the NO-synthase inhibitor L-NAME (50 mg/kg) also completely abolished the cardioprotective effect of delta-OR stimulation. The preliminary injection of DSLET but not of DAMGO prevented an increase in the level of diene conjugates and a decrease in the activity of superoxide dismutase (SOD) in the isolated myocardium tissue. Thus, the in vivo stimulation of delta-OR increased the tolerance of the heart to oxidative stress through activation of NO-synthase and SOD.
Rebrova
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TY
Laboratory of Experimental Cardiology, Research Institute of Cardiology, Siberian Branch of the Russian Academy of Medical Sciences, Tomsk, 634050, Russia. nuclear@cardio.tsu.ru
Maslov
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LN
Lishmanov
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Tam
S V
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D000818:Animals; D003402:Creatine Kinase / Q000187:drug effects / Q000378:metabolism*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D007275:Injections, Intravenous / Q000379:methods; D009206:Myocardium / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D010477:Perfusion / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D017465:Receptors, Opioid, delta / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000378:metabolism; D013482:Superoxide Dismutase / Q000187:drug effects
D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004743:Enkephalin, Leucine; C034318:enkephalin, Ser(2), Leu(5), Thr(6)-; C040643:N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D003402:Creatine Kinase; D019331:NG-Nitroarginine Methyl Ester