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

We have investigated the endothelin receptor subtypes mediating contra ction 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 concentrati on-dependent contractions of human saphenous vein, although [Ala(1,3,1 1,15)]endothelin-1 and sarafotoxin S6c only produced a contraction in similar to 50% of the preparations tested. The endothelin ET(A) recept or antagonist, BQ123 (D-Val,Leu,D-Trp,D-Asp,Pro; 10 mu M), antagonized endothelin-l-induced contractions with an estimated potency (pK(B) si milar to 6.0) which was an order of magnitude lower than reported prev iously 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 c ontraction in human saphenous vein.