Endothelin ETA and ETB receptors mediate vascular smooth muscle contraction.
1. We have investigated the receptors mediating endothelin-induced contraction of rabbit isolated jugular vein (RJV) and rat isolated thoracic aorta (RTA). 2. Endothelin-1 (ET-1) and endothelin-3 (ET-3) contracted RJV preparations with similar potency (EC50 values approximately 1 nM), whereas, ET-1 (EC50:4.5 nM) was approximately 80 fold more potent than ET-3 in contracting RTA. In addition, the ETB receptor-selective agonist [Ala1,3,11,15]ET-1 contracted RJV (EC50:2.1 nM) but not RTA. 3. The ETA receptor antagonist, BQ123, competitively antagonized (pA2 6.93) the contraction of RTA produced by ET-1, but had no effect (at 10 microM) on the contractile effects of either ET-1, ET-3 or [Ala1,3,11,15]ET-1 in RJV. 4. These data suggest that both ETA and ETB receptors can mediate vascular smooth muscle contraction.
Sumner
M J
MJ
Department of Cardiovascular and Respiratory Pharmacology, Glaxo Group Research Ltd., Ware, Herts.
Cannon
T R
TR
Mundin
J W
JW
White
D G
DG
Watts
I S
IS
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D016232:Endothelins / Q000494:pharmacology; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D007601:Jugular Veins / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010456:Peptides, Cyclic / Q000494:pharmacology*; D011817:Rabbits; D017466:Receptors, Endothelin / Q000187:drug effects*
D016232:Endothelins; D010456:Peptides, Cyclic; D017466:Receptors, Endothelin; C072247:cyclo(Trp-Asp-Pro-Val-Leu)