RESUMEN
Authors analyzed articles that opioids may aggravate ischemic and reperfusion damages of the heart but the opioid receptor antagonists may prevent these damages. Authors concluded the it is existed opioid receptor pool an activation of its decreases cardiac tolerance to an impact of ischemia-reperfusion.
Asunto(s)
Analgésicos Opioides/farmacología , Daño por Reperfusión Miocárdica/metabolismo , Antagonistas de Narcóticos/farmacología , Receptores Opioides/agonistas , Animales , Corazón/efectos de los fármacos , Humanos , Daño por Reperfusión Miocárdica/prevención & control , Antagonistas de Narcóticos/uso terapéutico , Receptores Opioides/metabolismoRESUMEN
The cardioprotective properties of a δ2-opioid receptor agonist deltorphin II were studied in rats with coronary occlusion and reperfusion. Opioid receptor ligands and inhibitors (glybenclamide, chelerythrine, and 5-hydroxydecanoate) were injected intravenously before ischemia and reperfusion. A δ2-opioid receptor agonist deltorphin II significantly decreased the infarction zone/risk zone index. This effect was abolished by naltrexone, naloxone methiodide, and δ2-opioid receptor antagonist naltriben, but not by a δ1-opioid receptor antagonist BNTX. The infarct-limiting effect of deltorphin II was not observed after inhibition of protein kinase C or blockade of mitochondrial K(ATP) channels.
Asunto(s)
Precondicionamiento Isquémico Miocárdico/métodos , Oligopéptidos/uso terapéutico , Canales de Potasio/fisiología , Proteína Quinasa C/fisiología , Receptores Opioides delta/fisiología , Animales , Benzofenantridinas/farmacología , Compuestos de Bencilideno/uso terapéutico , Ácidos Decanoicos/farmacología , Gliburida/farmacología , Hidroxiácidos/farmacología , Masculino , Daño por Reperfusión Miocárdica/metabolismo , Naltrexona/análogos & derivados , Naltrexona/uso terapéutico , Bloqueadores de los Canales de Potasio/farmacología , Proteína Quinasa C/antagonistas & inhibidores , Ratas , Ratas Wistar , Receptores Opioides delta/efectos de los fármacosRESUMEN
Intravenous pretreatment with kappa-opioid receptor antagonist (-)-U-50,488 (1 mg/kg) improved heart resistance to the arrhythmogenic effect of coronary occlusion and reperfusion. Selective kappa1-opioid receptor antagonist norbinaltorphimine and nonselective blocker of peripheral opioid receptors methylnaloxone abolished this antiarrhythmic effect. Preliminary blockade of protein kinase C with chelerythrine or inhibition of ATP-dependent K+ channels (K(ATP) channels) with glybenclamide abolished the antiarrhythmic effect of kappa-opioid receptor activation. Selective inhibitor of sarcolemmal K(ATP) channels did not modulate the kappa-opioid receptor-mediated increase in cardiac electrical stability. Our results suggest that protein kinase C and mitochondrial K(ATP) channels play an important role in the antiarrhythmic effect associated with activation of peripheral kappa-opioid receptors.