2 DIFFERENT ENDOTHELIN-B RECEPTOR SUBTYPES MEDIATE CONTRACTION OF THE RABBIT SAPHENOUS-VEIN

To study endothelin receptor subtypes that mediate venous smooth muscle contraction, effects of some endothelin receptor agonists and antagonists on the rabbit lateral saphenous vein were examined and compared with those on the saphenous artery. In the artery, endothelin (ET)-1 elicited concentration-dependent contractions, while selective ET(B)-receptor agonists, 1RL1620 (Suc-[Glu(9),Ala(11,15)ET-1(8-21)) and sarafotoxin 6c (S6c) had almost no effect. The ET-1-induced responses shifted in parallel to the right by BQ-123 (cycle (-D-Trp-D-Asp-Pro-D-Val-Leu-)), an ET(A)-receptor antagonist, or PD142893 (Ac-D-Dip-Leu-Asp-Ile-Ile-Trp), an ET(A)/ET(B)-receptor antagonist, indicating the involvement of the ET(A) receptor in this response. In the saphenous vein, not only ET-1 and ET-3, but also ET(B)-receptor agonists, IRL1620, S6c and [Glu(9)]sarafotoxin 6b ([Glu(9)]S6b), produced concentration-dependent, BQ-123-insensitive contractions. PD142893 did not affect the ET-l-induced contraction, but it shifted greatly the IRL1620-induced concentration-response curve in parallel to the right. The major components of ET-3-, S6c- and [Glu(9)]S6b-induced contractions were resistant to PD142893. These results indicate that two different vasoconstrictive ET(B)-receptor subtypes, ET(B1) (sensitive to IRL1620 and PD142893) and ET(B2) (insensitive to 1RL1620 and PD142893), are located on the smooth muscle of the saphenous vein.