Abstract
The effects of KRN4884 (5-amino-N-[2-(2-chrolophenyl)ethyl]-N′-cyano-3-pyridinecarboxamidine), a novel K+ channel opener, on the electrocardiogram changes caused by the intracoronary administration of endothelin-1 (ET-1) were studied in anesthetized rats and compared with the effects of levcromakalim, a K+ channel opener; nilvadipine, a Ca2+ antagonist; and propranolol, a β-adrenoceptor antagonist. KRN4884 (50 μg/kg, i.v.) and levcromakalim (300 μg/kg, i.v.) inhibited the ST segment elevation and the development of arrhythmias induced by ET-1 (5 μg, i.c.) and decreased the incidence of death. Nilvadipine (300 μg/kg, i.v.) and propranolol (1000 and 3000 μg/kg, i.v.) each prevented the ST segment elevation, but the suppressions of the occurrence of arrhythmias produced by nilvadipine and propranolol were less than that shown by KRN4884. KRN4884 (30 and 50 μg/kg, i.v.), levcromakalim (100 and 300 μg/kg, i.v.) and nilvadipine (100 and 300 μg/kg, i.v.) significantly decreased the mean blood pressure in a dose-dependent manner, but propranolol did not. The heart rate was decreased by nilvadipine (100 and 300 μg/kg, i.v.) and propranolol (1000 and 3000 μg/kg, i.v.), but was not affected by KRN4884 (30 and 50 μg/kg, i.v.) or levcromakalim (100 and 300 μg/kg, i.v.). These results suggest that pretreatments with KRN4884 and levcromakalim are more effective on ET-1-induced electrocardiogram changes than those with nilvadipine and propranolol.
