Vasoactivity mediated by endothelin ETA and ETB receptors in isolated porcine ophthalmic artery.
Endothelin isopeptides and sarafotoxin S6b induced strong contractions in isolated porcine ophthalmic artery at basal tension, which were antagonized in a concentration-dependent manner by the specific ETA antagonist FR 139317. The maximum contraction and potency of endothelin-1 and sarafotoxin S6b were similar, whereas endothelin-3 was significantly less potent and induced weaker contractions. Schild plot analysis was only obtained for endothelin-1 and sarafotoxin S6b, but indicated competitive binding at the same ETA receptor site for these peptides. However, the slope obtained for endothelin-1 was significantly less than unity, suggesting more than one receptor. FR 139317 was a more potent antagonist of contractions induced by endothelin-3 than the other peptides. In arteries pre-contracted by prostaglandin F2 alpha high endothelin-3 concentrations induced additional contraction, except in the presence of FR 139317 when a marked relaxation was observed, an ability which was otherwise marked by the strong contractile activity. The relaxation was significantly reduced in endothelin-denuded segments. Both contraction and relaxation were abolished by the ETA/B antagonist bosentan. The results suggest the presence of ETB as well as ETA receptors in this artery type, though ETB receptor activity is only demonstrated at an unusually high concentration of endothelin in this preparation in vitro.
White
L R
LR
Department of Neurology, University Hospital, Trondbeim, Norway.
Bakken
I J
IJ
Sjaavaag
I
I
Elsås
T
T
Vincent
M B
MB
Edvinsson
L
L
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D000077300:Bosentan; D015237:Dinoprost / Q000494:pharmacology; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D019334:Endothelin-3 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009880:Ophthalmic Artery / Q000187:drug effects / Q000502:physiology*; D017466:Receptors, Endothelin / Q000819:agonists / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology; D013552:Swine; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014757:Viper Venoms / Q000037:antagonists & inhibitors / Q000494:pharmacology
D001381:Azepines; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D019334:Endothelin-3; D007211:Indoles; D017466:Receptors, Endothelin; D013449:Sulfonamides; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6; C079574:FR 139317; D015237:Dinoprost; D000077300:Bosentan