HUMAN SAPHENOUS-VEIN CONTAINS BOTH ENDOTHELIN ET(A) AND ET(B) CONTRACTILE RECEPTORS

We have investigated the endothelin receptor subtypes mediating contraction in isolated preparations of human saphenous vein. Endothelin-1 (EC(50): 17.8 nM), endothelin-3 (EC(50): 82.3 nM) and the endothelin ET(B) receptor-selective agonists, [Ala(1,3,11,15)]endothelin-1 (EC(50): 63 nM) and sarafotoxin S6c (EC(50): 0.75 nM) all produced concentration-dependent contractions of human saphenous vein, although [Ala(1,3,11,15)]endothelin-1 and sarafotoxin S6c only produced a contraction in similar to 50% of the preparations tested. The endothelin ET(A) receptor antagonist, BQ123 (D-Val,Leu,D-Trp,D-Asp,Pro; 10 mu M), antagonized endothelin-l-induced contractions with an estimated potency (pK(B) similar to 6.0) which was an order of magnitude lower than reported previously for non-human isolated vascular tissues from other species (pA(2) values similar to 7.0). These data suggest that both endothelin ET(A) and endothelin ET(B) receptors can mediate vascular smooth muscle contraction in human saphenous vein.