Dexamethasone affects platelet aggregation and fibrinolytic activity in rats at different doses which is reflected by their effect on arterial thrombosis.
The effect of oral administration of dexamethasone to rats on the haemostatic system was investigated. Dexamethasone was given once daily for 5 consecutive days. Plasma PAI-1 antigen levels were increased dose dependently (up to 210 +/- 29% of control values at a dose of 3 mg/kg) whereas no significant effects on plasma t-PA antigen levels were observed (131 +/- 6% compared with control values). In addition, treatment with 1 mg/kg dexamethasone decreased t-PA activity in tissue extracts of the aorta, heart and liver (65%, 28% and 58%, respectively) whereas tissue u-PA activity was not influenced. In vivo fibrinolytic activity was significantly decreased after dexamethasone treatment at a dose of 3 mg/kg but not at a dose of 1 mg/kg. The effect of dexamethasone on in vivo platelet aggregation was studied in an arterial thrombosis model. Dexamethasone treatment resulted in a two-fold decrease in arterial thrombosis at a dose of 0.1 mg/kg. At a dose of 1 mg/kg a less pronounced but significant decrease was observed. We conclude that in haemostasis the primary effect of dexamethasone treatment is an inhibition of arterial thrombosis by inhibition of platelet aggregation which is neutralized at higher doses by a decreased fibrinolytic activity.
van Giezen
J J
JJ
Solvay Duphar B.V., Department of Vascular Pharmacology, Weesp, The Netherlands.
Brakkee
J G
JG
Dreteler
G H
GH
Bouma
B N
BN
Jansen
J W
JW
D000818:Animals; D001011:Aorta; D001760:Bleeding Time; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005342:Fibrinolysis / Q000187:drug effects*; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000097:blood
D017395:Plasminogen Activator Inhibitor 1; D010975:Platelet Aggregation Inhibitors; D003907:Dexamethasone; D010959:Tissue Plasminogen Activator