Antiaggregatory and hypotensive effects of endothelin-1 in beagle dogs: role for prostacyclin.
The effects of endothelin-1 (ET-1) on blood pressure and platelet aggregation were studied in anesthetized beagle dogs. Platelet aggregation was monitored in vivo by a filter-loop technique and in vitro by using platelet-rich plasma and whole blood. ET-1 (0.03-0.3 nmol/kg) induced a transient dose-dependent hypotension and inhibited platelet aggregation in vivo. These changes were accompanied by dose-dependent elevation of plasma 6-keto-PGF1 alpha levels. Pretreatment of animals with indomethacin (2 mg/kg plus 3 mg/kg/h) completely abolished the antiaggregatory action of ET-1 and significantly attenuated the hypotensive response to ET-1. Intra-arterial infusion of prostacyclin at concentrations similar to those observed following ET-1 injections mimicked the antiaggregatory and hypotensive actions of ET-1. ET-1 (0.1-100 nM) did not modify platelet aggregation induced by ADP, collagen, and platelet-activating factor in vitro, suggesting that dog platelets do not possess ET-1 receptors. These findings indicate that the antiaggregatory and hypotensive actions of ET-1 in beagle dogs are mediated through release of prostacyclin.
Filep
J G
JG
Department of Pathophysiology, Semmelweis University Medical School, Budapest, Hungary.
Hermán
F
F
Battistini
B
B
Chabrier
P E
PE
Braquet
P
P
Sirois
P
P
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011464:Epoprostenol / Q000096:biosynthesis / Q000502:physiology*; D005260:Female; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*
D000959:Antihypertensive Agents; D016232:Endothelins; D010975:Platelet Aggregation Inhibitors; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D007213:Indomethacin