Assuntos
Vacinas contra a AIDS/imunologia , Linfócitos B/imunologia , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/imunologia , HIV-1/imunologia , Linfócitos T/imunologia , Vacinas contra a AIDS/genética , Animais , Produtos do Gene env/imunologia , Produtos do Gene gag/imunologia , HIV-1/genética , Humanos , Imunidade Celular , Camundongos , Vacinas Combinadas , Vacinas de DNA/imunologia , Vacinas Virossomais/imunologia , Ligação ViralRESUMO
The rate and strength of heart contractions decreased after 10-min perfusion of rat myocardium with Krebs-Henseleit solution containing a selective cannabinoid receptor agonist HU-210 in a final concentration of 10 nM. HU-210 completely blocked the positive inotropic and chronotropic effect of beta-adrenoceptor agonist isoproterenol, decreased the basal level of cAMP, and abolished the isoproterenol-induced increase in myocardial cAMP concentration. cGMP concentration remained unchanged under these conditions. The decrease in myocardial cAMP concentration after activation of cannabinoid receptors did not correlate with changes in the strength and rate of heart contractions. Our results suggest that the negative inotropic and chronotropic effects of HU-210 are not associated with decreased cAMP concentration in the myocardium.
Assuntos
Agonistas de Receptores de Canabinoides , AMP Cíclico/fisiologia , GMP Cíclico/fisiologia , Dronabinol/análogos & derivados , Contração Miocárdica/efeitos dos fármacos , Agonistas Adrenérgicos beta/farmacologia , Animais , AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Dronabinol/farmacologia , Técnicas In Vitro , Isoproterenol/farmacologia , Masculino , Miocárdio/metabolismo , Radioimunoensaio , RatosRESUMO
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
It has been found that prior intravenous administration of the endocannabinoid anandamide (10 mg/kg) or its synthetic analogue R-(+)-methanadamide (5 mg/kg) prevents a development of ischemic and reperfusion arrhythmias in rats. The prior injection of the CB1 receptor antagonist, SR 141716A (3 mg/kg), did no affect the antiarrhythmic action of both cannabinoids. Pretreatment with the CB2 receptor antagonist, SR 144528 (1 mg/kg), completely abolished antiarrhythmic effect of anandamide and R-(+)-methanandamide. Both CB antagonist had no effect on the arrhythmias itself. Pretreatment with the NO-synthase inhibitor, L-NAME (50 mg/kg), had no effect on the antiarrhythmic action of cannabinoids. We therefore conclude that CB2 receptor stimulation increases the heart tolerance to ischemic and reperfusion arrhythmias.
