The involvement of AT(2)-receptor in the antithrombotic effect of losartan in renal hypertensive rats.
In previous studies, we have shown that losartan possesses nitric oxide-dependent antithrombotic properties in various models of hypertension in rats. It was demonstrated that stimulation of AT2-receptors plays an important role in the pharmacological effects of AT1-receptor antagonists. Thus, in this study, we examine the participation of AT2-receptors in the antithrombotic action of losartan in renal hypertensive rats on venous thrombosis induced by a two-hour ligation of the vena cava. Losartan administration(30 mg/kg, p.o.) resulted in a marked decrease in thrombus weight (by 85%, p<0.001). PD123319, an AT2-receptor antagonist (10 mg/kg, i.v.), administered concomitantly with losartan, abolished its antithrombotic effect, whilst it had no influence on thrombus weight when given alone. A significant decrease in systolic blood pressure was observed in animals given losartan. PD123319 administration didnot abolish this action of losartan and did not alter blood pressure when given alone. No changes in prothrombin time, activated partial thromboplastin time, or euglobulin clot lysis time were observed in animals administered losartan and/or PD123319.Similarly, primary haemostatics evaluated by bleeding time and platelet count did not change in any group of rats. In conclusion, we have shown that AT2-receptor stimulation is involved in the antithrombotic action of losartan in renal hypertensive rats.
Chabielska
E
E
Department of Pharmacodynamics, Medical Academy, Mickiewicza Str.2C, 15-230, Poland. chabewa@poczta.onet.pl
Matys
T
T
Kucharewicz
I
I
Pawlak
D
D
Rólkowski
R
R
Buczko
W
W
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006978:Hypertension, Renovascular / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology; D008026:Ligation; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000819:agonists / Q000502:physiology*; D014684:Venae Cavae; D020246:Venous Thrombosis / Q000517:prevention & control*
D000959:Antihypertensive Agents; D005343:Fibrinolytic Agents; D007093:Imidazoles; D011725:Pyridines; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; C073402:PD 123319; D019808:Losartan