THE ET(A) ANTAGONIST BQ-123 INHIBITS ANOXIC CONTRACTIONS OF CANINE CORONARY-ARTERIES WITHOUT ENDOTHELIUM

Experiments were designed to determine whether or not endogenous endot helin (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 less-than -or-equal-to 1 mm Hg) caused reproducible contractions. The anoxic con tractions were augmented by exogenous endothelin-1 (ET-1). At 10(-6) M and 10(-5) M, BQ-123 (a specific endothelin antagonist) inhibited bot h the facilitatory effect of ET-1 and the anoxic contractions. At thes e concentrations BQ-123 caused a parallel shift to the right of the co ncentration-response curve to ET-1 and a small but significant depress ion of the response to norepinephrine, without affecting the maximal r esponse to the catecholamine. BQ-123 did not significantly affect the concentration-response curve to Ca2+ in depolarizing solution (60 mM K Cl). Monoclonal antibodies against ET-1 (70 mug/ml) inhibited the resp onse to exogenous ET-1 and abolished the facilitating effect of the pe ptide, but did not affect the anoxic contractions. These results sugge st that ET-1 contributes to anoxic contractions in canine coronary art eries without endothelium. The receptor involved belongs to the ET(A)- subtype and is not accessible to monoclonal antibodies.