Endothelin-1 and unstable angina: effect of either endothelin ET(A) or ET(B) receptor antagonism in a locally injured canine coronary artery

The role of endogenous endothelin-1 in variant angina was investigated using two endothelin receptor antagonists: LU 135252 (ET(A)) and BQ 788 (ET(B)). Cyclic flow reductions were induced in a coronary artery of mongrel dogs by combining critical stenosis with endothelial injury. One hour after induction of cyclic coronary flow reductions the dogs were randomized to intravenous treatment with either saline, or LU 135252 (10 mg kg(-1)), or BQ 788 (0.1 mg kg(-1)). Cyclic coronary flow reductions were monitored for two hours after drug and remained constant in controls as well as after BQ 788. LU 135252 reduced the number of cyclic coronary flow reductions significantly (about 50%) without effects on hemodynamics or hemostasis.