ET(B)-type receptors mediate endothelin stimulated contraction in the aortic vascular smooth muscle of the spiny dogfish shark, Squalus acanthias

Using various agonists, and the specific antagonist BQ-123, we have examined the sensitivity to endothelin of the vascular smooth muscle of the ventral aorta of the spiny dogfish shark, Squalus acanthias. Human endothelin-l produced significant contraction of isolated vascular smooth muscle rings, with an EC(50) of 10 nmol . 1(-1). The presence of an intact endothelium did not alter this response but the magnitude of the contraction was greater in rings with an intact endothelium. The response to 0.2 mu mol . 1(-1) endothelin-1 was equivalent to that of 0.1 mmol . 1(-1) acetylcholine, and significantly greater than that to 80 mmol . 1(-1) KCI, suggesting high sensitivity even to the heterologous, mammalian peptide. The Hill plot of the contractile response was a straight line with a slope of 1.12, indicating that a single receptor was mediating the response. Endothelin-l, endothelin-3, and sarafotoxin S6c produced similar concentration-response curves, and the response to endothelin-l was insensitive to the ET(A)-specific inhibitor BQ-123. Our data are consistent with the hypothesis that the receptor involved in the contractile response to endothelin of shark aortic vascular smooth muscle is of the ET(B)-rather than the ET(A)-type.