Cardiovascular effects of E4080, a novel bradycardiac agent with coronary vasodilating properties, in anesthetized dogs.

The cardiohemodynamic effects of E4080, a novel bradycardiac agent with a coronary vasodilating feature, were studied in anesthetized open-chest dogs. E4080 (0.3 and 1 mg/kg i.v.) decreased heart rate (HR), mean aortic pressure (MAP) and total peripheral resistance, and increased coronary blood flow (CBF) without affecting cardiac output and the electrocardiogram. The maximum rate of rise in left ventricular pressure decreased at 1 mg/kg. In addition, E4080 (0.3 and 1 mg/kg i.v.) decreased myocardial oxygen consumption. On administration in sinus node artery, E4080 (10 and 30 micrograms) selectively decreased HR. Glibenclamide, an ATP-sensitive K+ channel blocker (5 mg/kg i.v.), inhibited both the increase in CBF and the decrease in MAP caused by E4080 (1 mg/kg i.v.) but did not inhibit the bradycardia. These results suggested that E4080 has both bradycardiac and coronary vasodilating effects, and that activation of ATP-sensitive K+ channel contributes to the vasodilating action of E4080 but not to the bradycardiac action.