In vivo antiaggregatory action of platelet-activating factor in beagle dogs: role for prostacyclin.
The effects of platelet-activating factor (PAF) on in vivo platelet aggregation were studied in anaesthetized beagle dogs by using the extracorporeal filter-loop technique. Intraarterial administration of PAF caused an immediate increase in filter pressure, indicating enhanced in vivo platelet aggregation. Intravenous administration of PAF (3-100 ng kg-1) resulted in a transient dose-dependent inhibition of spontaneous platelet aggregation on the filter with concomitant elevation in plasma 6-keto-PGF1 alpha levels. These changes were significantly attenuated by pretreatment of the animals either with BN 52021 (4 mg kg-1), a specific PAF receptor antagonist or with acetylsalicylic acid (25 mg kg-1). Intraarterial infusion of exogenous prostacyclin at concentrations similar to those observed following intravenous PAF administration, resulted in a transient inhibition of the spontaneous platelet aggregation. These data provide evidence for prostacyclin release in response to PAF, and suggest that prostacyclin may mediate the in vivo anti-aggregatory action of PAF in anaesthetized dogs.
Hermán
F
F
Department of Pharmacodynamics and Pathophysiology, Semmelweis University Medical School, Budapest, Hungary.
Magyar
K
K
Filep
J G
JG
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D004285:Dogs; D011464:Epoprostenol / Q000502:physiology*; D005260:Female; D008297:Male; D010972:Platelet Activating Factor / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors
D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol