Antithrombotic activity of losartan in two kidney, one clip hypertensive rats. A study on the mechanism of action.
The potential antithrombotic action of losartan, an AT1 receptor antagonist, administered to two-kidney, one-clip rats (2K1C) in an experimental model of venous thrombosis was evaluated. The involvement of nitric oxide (NO) in this effect was also studied. Venous stasis was induced by ligation of the vena cava. Losartan after single dose (10 mg/kg, p.o.) significantly reduced the venous thrombus growth. The antithrombotic action of losartan in 2K1C rats was abolished by N(G)-nitro-L-arginine methyl ester (L-NAME, 30 mg/kg s.c.) and restored by L-arginine (1000 mg/kg s.c.). Platelet adhesion to fibrillar collagen significantly decreased after administration of losartan. No changes in primary hemostasis and platelet aggregation were observed. Moreover, coagulation parameters such as activated partial thromboplastin time, prothrombin time and euglobulin clot lysis time were found unchanged after losartan administration either in systemic circulation or at the place of thrombus formation. Our results indicate that antithrombotic activity of losartan in 2K1C rats is NO--dependent; observed inhibition of platelet adhesion could also play a role in this phenomenon.
Chabielska
E
E
Department of Pharmacodynamics, Medical University, Białystok, Poland.
Pawlak
R
R
Wollny
T
T
Rółkowski
R
R
Buczko
W
W
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects; D004195:Disease Models, Animal; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006977:Hypertension, Renal / Q000188:drug therapy*; D007668:Kidney / Q000187:drug effects*; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D020246:Venous Thrombosis / Q000188:drug therapy
D057911:Angiotensin Receptor Antagonists; D005343:Fibrinolytic Agents; D009569:Nitric Oxide; D019808:Losartan