Prophylactic intravenous (i.v.) injections of a selective agonist of ORL1 receptors nociceptin (orphanin FQ) in a dose of 0.4 mg/kg prevented the development of aconitine-induced arrhythmia in rats narcotized with diethyl ether or chloralose. Pretreatment with L-NAME (50 mg/kg) completely abolished this effect of orphanin FQ, while the pretreatment with indomethacin (10 mg/kg) only attenuated the agonist effect, rather than abolished it completely. At the same time, pretreatment with hexamethonium (10 mg/kg) or glibenclamide (3 mg/kg) had no effect on the nociceptin-dependent cardiac tolerance to the arrhythmogenic action of aconitine. Intracerebroventricular (i.c.v.) infusion of orphanin FQ (36 microg) also prevented the onset of aconitine-induced arrhythmia, but this effect was completely abolished by hexamethonium. It is concluded that the antiarrhythmic action of nociceptin with respect to aconitine-induced arrhythmia upon i.v. and i.c.v. administration is explained by different mechanisms. In the former case, the effect of orphanin FQ is related to the activation of NO synthase and cyclooxygenase, while the central action involves the vegetative nervous system.
Animals Anti-Arrhythmia Agents