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

To study endothelin receptor subtypes that mediate venous smooth muscl e contraction, effects of some endothelin receptor agonists and antago nists on the rabbit lateral saphenous vein were examined and compared with those on the saphenous artery. In the artery, endothelin (ET)-1 e licited concentration-dependent contractions, while selective ET(B)-re ceptor agonists, 1RL1620 (Suc-[Glu(9),Ala(11,15)ET-1(8-21)) and sarafo toxin 6c (S6c) had almost no effect. The ET-1-induced responses shifte d in parallel to the right by BQ-123 (cycle (-D-Trp-D-Asp-Pro-D-Val-Le u-)), an ET(A)-receptor antagonist, or PD142893 (Ac-D-Dip-Leu-Asp-Ile- Ile-Trp), an ET(A)/ET(B)-receptor antagonist, indicating the involveme nt 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-dependen t, BQ-123-insensitive contractions. PD142893 did not affect the ET-l-i nduced contraction, but it shifted greatly the IRL1620-induced concent ration-response curve in parallel to the right. The major components o f ET-3-, S6c- and [Glu(9)]S6b-induced contractions were resistant to P D142893. 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 smoot h muscle of the saphenous vein.