Activation of type II cannabinoid receptors improves myocardial tolerance to arrhythmogenic effects of coronary occlusion and reperfusion.
Preliminary intravenous injection of cannabinoid receptor agonist HU-210 (0.05 mg/kg) reduced the incidence of ventricular arrhythmias during 10-min coronary occlusion and 10-min reperfusion in chloralose-anesthetized rats. Preliminary injection of type I cannabinoid receptor antagonist SR 141716A (3 mg/kg) had no effect on the antiarrhythmic effect of HU-210, while type II cannabinoid receptor antagonist SR 144528 (1 mg/kg) completely abolished the effect of HU-210. Preconditioning with glibenclamide (0.3 mg/kg), an inhibitor of ATP-dependent K(+)-channels, did not affect the antiarrhythmic activity of HU-210. These findings suggest that antiarrhythmic effect of HU-210 is mediated through activation of type II cannabinoid receptors rather than activation of K(+)-channels.
Krylatov
A V
AV
Institute of Cardiology, Tomsk Scientific Center, Siberian Division of Russian Academy of Medical Sciences.
Ugdyzhekova
D S
DS
Bernatskaya
N A
NA
Maslov
L N
LN
Mekhoulam
R
R
Pertwee
R G
RG
Stephano
G B
GB
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology / Q000627:therapeutic use; D002186:Cannabinoids / Q000494:pharmacology / Q000627:therapeutic use; D003327:Coronary Disease / Q000503:physiopathology; D013759:Dronabinol / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D006321:Heart / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000819:agonists / Q000502:physiology*
D000889:Anti-Arrhythmia Agents; D002186:Cannabinoids; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D013759:Dronabinol; C062018:HU 211