The ETA antagonist BQ-123 inhibits anoxic contractions of canine coronary arteries without endothelium.
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 < or = 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 micrograms/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 ETA-subtype and is not accessible to monoclonal antibodies.
Vedernikov
Y P
YP
Center for Experimental Therapeutics, Baylor College of Medicine, Houston, Texas.
Goto
K
K
Vanhoutte
P M
PM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D003331:Coronary Vessels / Q000502:physiology; D004285:Dogs; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000276:immunology / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010456:Peptides, Cyclic / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D010456:Peptides, Cyclic; C072247:cyclo(Trp-Asp-Pro-Val-Leu)