COMPARISON OF CORONARY DILATING EFFECTS OF KI1769, A NEW K-CHANNEL OPENER OF THE PYRIDINECARBOXIMIDAMIDE TYPE, AND NIFEDIPINE IN ANESTHETIZED DOGS

The coronary dilating effect of a new type of K channel opener, N-cyan o-N'-(2-phenethyl)-3-pyridinecarboximidamide (Ki1769), was examined in anesthetized dogs in comparison with that of nifedipine. Administrati on of Ki1769 (30 and 100 mug/kg, i.v.) and nifedipine (1 and 3 mug/kg, i.v.) produced a dose-dependent decrease of mean blood pressure with a concomitant increase in heart rate. Ki1769 and nifedipine dose-depen dently increased coronary blood flow and aortic blood flow and decreas ed coronary vascular resistance and total peripheral vascular resistan ce. The percentage decrease of coronary vascular resistance was greate r than that of total peripheral vascular resistance with Ki1769 and ni fedipine, but Ki1769 showed a greater specificity in the decrease of c oronary vascular resistance than nifedipine. Glibenclamide (5 mg/kg, i .v.) inhibited these hemodynamic effects of Ki1769 but did not affect those of nifedipine. These results suggest that the preferential effec t of Ki1769 on the coronary vascular bed is greater than that of nifed ipine. Such a profile of Ki1769 is based on its K channel-opening acti on.