E. Chabielska et al., LOSARTAN INHIBITS EXPERIMENTAL VENOUS THROMBOSIS IN SPONTANEOUSLY HYPERTENSIVE RATS, Thrombosis research, 90(6), 1998, pp. 271-278
The potential antithrombotic action of losartan, the AT(1) receptor an
tagonist, in an experimental model of venous thrombosis in spontaneous
ly hypertensive rats (SHR) and Wistar Kyoto rats (WKY) was tested. The
involvement of nitric oxide and prostacyclin in this effect was also
studied. Venous stasis was induced by ligation of the vena cava. Losar
tan, after administration of a single, hypotensive dose (10 mg/kg, p.o
.), significantly reduced the thrombus weight in SHR but not in WKY. T
he antithrombotic activity of losartan in SHR was abolished by NG-nitr
o L-arginine methyl ester (L-NAME) (30 mg/kg s.c.) but not by indometh
acin (2.5 mg/kg s.c.). No changes in primary hemostasis, platelet aggr
egation, coagulation parameters such as activated partial thromboplast
in time, prothrombin time, euglobulin clot lysis time, and fibrinogen
level, either in SHR or in WKY rats, were found. Our results indicate
the NO-dependent mechanism in the antithrombotic effect of losartan on
venous thrombosis in SHR. (C) 1998 Elsevier Science Ltd.