The ET(A) antagonist BQ-123 inhibits anoxic contractions of canine coronary arteries without endothelium

Abstract

Experiments were designed to determine whether or not endogenous endothelin (ET) contributes to endothelium-independent anoxic contractions of canine coronary arteries. Rings without endothelium were suspended for isometric tension recording in conventional organ chambers filled with modified Krebs-Ringer bicarbonate solution. Anoxia (PO2 ≤1 mm Hg) caused reproducible contractions. The anoxic contractions were augmented by exogenous endothelin-1 (ET-1). At 10-6 M and 10-5 M, BQ-123 (a specific endothelin antagonist) inhibited both the facilitatory effect of ET-1 and the anoxic contractions. At these concentrations BQ-123 caused a parallel shift to the right of the concentration-response curve to ET-1 and a small but significant depression of the response to norepinephrine, without affecting the maximal response to the catecholamine. BQ-123 did not significantly affect the concentration-response curve to Ca2+ in depolarizing solution (60 mM KCl). Monoclonal antibodies against ET-1 (70 μg/ml) inhibited the response to exogenous ET-1 and abolished the facilitating effect of the peptide, but did not affect the anoxic contractions. These results suggest that ET-1 contributes to anoxic contractions in canine coronary arteries without endothelium. The receptor involved belongs to the ET(A)-subtype and is not accessible to monoclonal antibodies.