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.