The endothelin receptor antagonist, BQ-123, inhibits angiotensin II-induced contractions in rabbit aorta

The purpose of this study was to examine the specificity of the cyclic pentapeptide ET A receptor antagonist BQ-123. BQ-123 competitively antagonized endothelin-1-induced contractions in rabbit aorta, increases in inositol phosphates in cultured rat vascular smooth muscle A10 cells, and binding of [ 125 I]endothelin-1 to the cloned ET A receptor cDNA expressed in Cos 7 cells. In contrast, BQ-123 was a weak antagonist of [ 125 I]endothelin-3 binding to rat cerebellar membranes and to membranes from Cos 7 cells transfected with the cloned ET B receptor cDNA. BQ-123 shifted concentration-response curves in isolated rabbit aorta elicited by angiotensin II, but did not bind to angiotensin II receptors nor affect angiotensin II-induced increases in inositol phosphates. BQ-123 also did not affect contractions induced by KCl or norepinephrine. These data suggest that endothelin may play a role in angiotensin II-induced contractions of rabbit aorta.