Human saphenous vein contains both endothelin ETA and ETB contractile receptors.
We have investigated the endothelin receptor subtypes mediating contraction in isolated preparations of human saphenous vein. Endothelin-1 (EC50: 17.8 nM), endothelin-3 (EC50: 82.3 nM) and the endothelin ETB receptor-selective agonists, [Ala1,3,11,15]endothelin-1 (EC50: 63 nM) and sarafotoxin S6c (EC50: 0.75 nM) all produced concentration-dependent contractions of human saphenous vein, although [Ala1,3,11,15]endothelin-1 and sarafotoxin S6c only produced a contraction in approximately 50% of the preparations tested. The endothelin ETA receptor antagonist, BQ123 (D-Val,Leu,D-Trp,D-Asp,Pro; 10 microM), antagonized endothelin-1-induced contractions with an estimated potency (pKB approximately 6.0) which was an order of magnitude lower than reported previously for non-human isolated vascular tissues from other species (pA2 values approximately 7.0). These data suggest that both endothelin ETA and endothelin ETB receptors can mediate vascular smooth muscle contraction in human saphenous vein.
White
D G
DG
Pharmacology Division, Glaxo Research and Development Ltd., Ware, Herts, UK.
Garratt
H
H
Mundin
J W
JW
Sumner
M J
MJ
Vallance
P J
PJ
Watts
I S
IS
D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology; D006801:Humans; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010456:Peptides, Cyclic / Q000494:pharmacology; D017466:Receptors, Endothelin / Q000378:metabolism*; D012501:Saphenous Vein / Q000187:drug effects / Q000378:metabolism*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014757:Viper Venoms / Q000494:pharmacology
D016232:Endothelins; D010456:Peptides, Cyclic; D017466:Receptors, Endothelin; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6; C072247:cyclo(Trp-Asp-Pro-Val-Leu)