[Interactions of peripheral mu-opioid receptors and K(ATP)-channels in regulation of cardiac electrical stability in ischemia, reperfusion, and postinfarction cardiosclerosis].
It has been shown that mu-opioid receptor stimulation by intravenous administration of the selective mu receptor agonist DALDA in a dose of 0.1 mg/kg prevented ischemic and reperfusion arrhythmias in rats subjected to coronary artery occlusion (10 min) and reperfusion (10 min), and also increased the ventricular fibrillation threshold in rats with postinfarction cardiac fibrosis. These effects were abolished by pre-treatment with the selective mu receptor antagonist CTAP in a dose of 0.5 mg/kg or by prior injection of the opioid receptor antagonist naloxone methiodide (2 mg/kg) which does not penetrate the blood-braib barrier. Both antagonists by themselves had no effect on the incidence of occlusion or reperfusion-induced arrhythmias or on the ventricular fibrillation threshold. Pre-treatment with ATP-sensitive K+ channel (KATP channel) blocker glibenclamide in a dose of 0.3 mg/kg completely abolished the antiarrhythmic effect of DALDA. We believe that DALDA prevents occurrence of electrical instability during ischemia and reperfusion and increases the ventricular fibrillation threshold in rats with postinfarction cardiac fibrosis via stimulation of peripheral mu-opioid receptor which appear to be coupled to the KATP channel.
Maslov
L N
LN
Institute of Cardiology, 111 Kievskaya St., 634050 Tomsk, Russia.
Krylatov
A V
AV
Naryzhaia
N V
NV
Solenkova
N V
NV
Lishmanov
A Iu
AIu
Bogomaz
S A
SA
Gross
G J
GJ
Stefano
J B
JB
Loktiushina
B A
BA
D000818:Animals; D004562:Electrocardiography; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D009270:Naloxone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments; D010455:Peptides / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D000644:Quaternary Ammonium Compounds; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D012598:Sclerosis; D013004:Somatostatin
C529311:CTAP octapeptide; D009842:Oligopeptides; D010446:Peptide Fragments; D010455:Peptides; D015221:Potassium Channels; D000644:Quaternary Ammonium Compounds; D017450:Receptors, Opioid, mu; C063076:tyrosyl-arginyl-phenylalanyl-lysinamide; D009270:Naloxone; D013004:Somatostatin; C041269:N-methylnaloxone