Prostanoids stimulate fibrinolysis in the rat.
Fibrinolysis was assessed in urethane-anaesthetized rats challenged by bolus intravenous injection of eicosanoids. A sensitive fibrin plate bioassay was used for this purpose. Classical prostanoids such as PGE2, PGI2, PGD2 and PGF2 alpha produced a dose-related increase in fibrinolysis in the rat which was first evident 15 min post-injection and remained increased until 75 min when experiments were concluded. 6 oxo PGE1, the stable enzymatic metabolite of PGI2, exhibited similar pro-fibrinolytic activity in the rat. The rank order of potency was PGE2 greater than 6 oxo PGE1 greater than PGD2 greater than PGF2 alpha. Neither saline nor Tris-HCl buffer stimulated fibrinolysis. Furthermore, the chemical hydrolysis product of PGI2, 6 oxo PGF1 alpha, and the enzymatic metabolite of PGE2, 15 oxo PGE2, were inactive at doses up to 50 micrograms/kg. LtC4 was also inactive at doses up to 25 micrograms/kg. None of the prostanoids used in this study stimulated fibrinolysis when applied directly to fibrin plates at doses up to 50 micrograms. Prostanoids may owe some of their clinical efficacy in cardiovascular disorders to stimulation of blood fibrinolytic activity.
Moore
P K
PK
Department of Pharmacology, King's College, University of London, England.
Hussaini
I
I
Bhardwaj
R
R
D000818:Animals; D005342:Fibrinolysis / Q000187:drug effects*; D005916:Globulins / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D011453:Prostaglandins / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D005916:Globulins; D011453:Prostaglandins