Effects of KRN4884 (a novel K+ channel opener), levcromakalim, nilvadipineand propranolol on endothelin-1-induced heart disorders in anesthetized rats

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