The in vivo antiaggregatory action of endothelin-1 is not mediated through the endothelin ETA receptor.
Intravenous bolus injection of endothelin-1 (0.1 and 0.25 nmol/kg) resulted in a dose-dependent inhibition of in vivo platelet aggregation in anesthetized Beagle dogs. Pretreatment of the animals with the selective ETA receptor antagonist, BQ-123 (1 mg/kg), completely abolished the pressor response to endothelin-1 without affecting the magnitude of the depressor response. BQ-123 neither modified the antiaggregatory action of endothelin-1 nor affected the increase in plasma 6-keto prostaglandin F1 alpha level elicited by endothelin-1. These findings indicate that the in vivo antiaggregatory and prostacyclin releasing actions of endothelin-1 are not mediated by activation of the ETA receptor.
Hermán
F
F
Department of Pharmacodynamics, Semmelweis University Medical School, Budapest, Hungary.
Yano
M
M
Filep
J G
JG
D015121:6-Ketoprostaglandin F1 alpha / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D016232:Endothelins / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008297:Male; D010456:Peptides, Cyclic / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D017466:Receptors, Endothelin / Q000187:drug effects* / Q000502:physiology
D016232:Endothelins; D010456:Peptides, Cyclic; D010975:Platelet Aggregation Inhibitors; D017466:Receptors, Endothelin; D015121:6-Ketoprostaglandin F1 alpha; C072247:cyclo(Trp-Asp-Pro-Val-Leu)