RESUMO
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.
Assuntos
Ácidos Araquidônicos/farmacologia , Arritmias Cardíacas/metabolismo , Coração/efeitos dos fármacos , Isquemia Miocárdica/metabolismo , Animais , Antiarrítmicos/farmacologia , Ácidos Araquidônicos/química , Bloqueadores dos Canais de Cálcio/química , Bloqueadores dos Canais de Cálcio/farmacologia , Canabinoides/química , Canabinoides/farmacologia , AMP Cíclico/metabolismo , Endocanabinoides , Inibidores Enzimáticos/farmacologia , Glibureto/farmacologia , Masculino , Miocárdio/metabolismo , NG-Nitroarginina Metil Éster/farmacologia , Alcamidas Poli-Insaturadas , Canais de Potássio/metabolismo , Ratos , Ratos Wistar , Receptores de Canabinoides , Receptores de Droga/metabolismoRESUMO
We studied the possibility of decreasing the area of ischemic necrosis during myocardial infarction with HU-210, a selective cannabinoid receptor agonist. Activation of cannabinoid receptors with HU-210 had practically no effect on collateral blood flow in the myocardium, but considerably decreased the area of necrosis. There results indicate that cannabinoid receptor agonist HU-210 possesses cardioprotective activity and delays the formation of necrotic zones during coronary occlusion and reperfusion.
Assuntos
Dronabinol/análogos & derivados , Isquemia Miocárdica/metabolismo , Miocárdio/metabolismo , Receptores de Droga/metabolismo , Animais , Cardiotônicos/farmacologia , Dronabinol/farmacologia , Coração/efeitos dos fármacos , Masculino , Isquemia Miocárdica/patologia , Miocárdio/patologia , Necrose , Ratos , Ratos Wistar , Receptores de Canabinoides , Receptores de Droga/agonistasRESUMO
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.
Assuntos
Coração/fisiopatologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Receptores de Droga/fisiologia , Animais , Antiarrítmicos/farmacologia , Antiarrítmicos/uso terapêutico , Canabinoides/farmacologia , Canabinoides/uso terapêutico , Doença das Coronárias/fisiopatologia , Dronabinol/análogos & derivados , Dronabinol/farmacologia , Dronabinol/uso terapêutico , Reperfusão Miocárdica , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Ratos , Ratos Wistar , Receptores de Canabinoides , Receptores de Droga/agonistasRESUMO
Intravenous injection of 10 mg/kg anandamide reduces the incidence and duration of epinephrine-induced arrhythmias in rats. SR141716A and SR144528, antagonists of cannabinoid receptor I and II did not abolish the antiarrhythmic effect of anandamide. These data suggest that the antiarrhythmic effect of anandamide is nonspecific or mediated via unknown cannabinoid receptors, but not associated with activation of cannabinoid receptors I and II.
