Endogenous cannabinoids improve myocardial resistance to arrhythmogenic effects of coronary occlusion and reperfusion: a possible mechanism.
Stimulation of cannabinoid receptors with endogenous cannabinoid anandamide and its enzyme-resistant analogue R-(+)-methanandamide improved cardiac resistance to arrhythmias induced by coronary occlusion and reperfusion. This antiarrhythmic effect was not associated with activation of NO synthase, since pretreatment with NG-nitro-L-arginine methyl ester had no effect on the incidence of ischemia/reperfusion-induced arrhythmias. Blockade of ATP-dependent K+ channels with glybenclamide did not abolish the antiarrhythmic effect of R-(+)-methanandamide. Antiarrhythmic activity of endogenous cannabinoids is probably associated with their direct effects on the myocardium.
Krylatov
A V
AV
Institute of Cardiology, Tomsk Research Center, Siberian Division of the Russian Academy of Medical Sciences.
Uzhachenko
R V
RV
Maslov
L N
LN
Bernatskaya
N A
NA
Makriyannis
A
A
Mechoulam
R
R
Pertwee
R G
RG
Sal'nikova
O M
OM
Stefano
J B
JB
Lishmanov
YuB
Y
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001095:Arachidonic Acids / Q000737:chemistry / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000494:pharmacology; D002186:Cannabinoids / Q000737:chemistry / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D063388:Endocannabinoids; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D053284:Polyunsaturated Alkamides; D015221:Potassium Channels / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000378:metabolism
D000889:Anti-Arrhythmia Agents; D001095:Arachidonic Acids; D002121:Calcium Channel Blockers; D002186:Cannabinoids; D063388:Endocannabinoids; D004791:Enzyme Inhibitors; D053284:Polyunsaturated Alkamides; D015221:Potassium Channels; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D000242:Cyclic AMP; D005905:Glyburide; C078814:anandamide; D019331:NG-Nitroarginine Methyl Ester