Abstract
Effect of efonidipine, a long-acting dihydropyridine derivative, on the endothelin-1 (ET-1)-induced coronary vasoconstriction was studied in open-chest anesthetized dogs. Efonidipine (0.03 or 0.1 mg/kg) was administered i.v. 10 min before an intracoronary injection of ET-1 (30 pmol/kg). An intracoronary injection of ET-1 decreased coronary blood flow (CBF) that was measured by a flow probe. The ET-1-induced decrease in CBF was sustained for more than 30 min without significant changes in blood pressure and heart rate. Pretreatment with efonidipine attenuated the decrease in CBF induced by ET-1 significantly and dose-dependently. ET-1 also reduced coronary diameter for more than 30 min as evaluated by the coronary angiography technique. Pretreatment with efonidipine also attenuated the reduction in coronary diameter induced by ET-1 significantly and dose-dependently. These effects of efonidipine were sustained for at least 30 min after the ET-1 administration. It is concluded that efonidipine attenuates the ET-1-induced vasoconstriction, and therefore the drug would be useful for some patients with variant angina, in which ET-1 is involved in the genesis of coronary vasoconstriction.
