Effect of in vivo and in vitro stimulation of delta1-opioid receptors on myocardial resistance to arrhythmogenic action of ischemia and reperfusion.
Preliminary intravenous injection of peptide agonist of delta1-opioid receptors DPDPE (0.5 mg/kg) decreased the incidence of occlusion (10 min) and reperfusion (10 min) arrhythmias in rats. By contrast, delta2-opioid receptor agonist DSLET produced no effect on the incidence of arrhythmias provoked by coronary occlusion and reperfusion. Preliminary injection of selective delta-receptor antagonist ICI 174,864 (2.5 mg/kg) or TIPP[y] (0.5 mg/kg) completely abolished the antiarrhythmic effect of DPDPE. Stimulation of cardiac delta1-opioid receptors with DPDPE added to perfusion saline in concentrations of 0.1 and 0.5 mg/liter decreased the incidence of reperfusion arrhythmias. Addition of DPDPE to perfusion saline in a concentration of 0.1 mg/liter prevented reoxygenation destruction of cardiomyocytes. By contrast, no cardioprotective effect of this peptide was observed at a concentration of 0.5 mg/liter in perfusion saline or when it was injected intravenously. It is concluded that the cardioprotective and antiarrhythmic effects of DPDPE are caused by activation of cardiac delta1-opioid receptors.
Lasukova
T V
TV
Laboratory of Experimental Cardiology, Institute of Cardiology, Tomsk Research Center, Siberian Division of the Russian Academy of Medical Sciences, Russia.
Krylatov
A V
AV
Maslov
L N
LN
Lishmanov
Yu B
YB
Gross
G J
GJ
Stefano
G B
GB
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000494:pharmacology; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D017202:Myocardial Ischemia / Q000150:complications* / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000378:metabolism*
D000889:Anti-Arrhythmia Agents; D009292:Narcotic Antagonists; D009842:Oligopeptides; D017465:Receptors, Opioid, delta; C092721:tyrosyl-tetrahydroisoquinolinecarbonyl-psi(methylamino)phenylalanyl-phenylalanine; D004743:Enkephalin, Leucine; C034318:enkephalin, Ser(2), Leu(5), Thr(6)-; D020881:Enkephalin, D-Penicillamine (2,5)-; C040643:N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine