The involvement of AT2-receptor in the antithrombotic effect of losartan in renal hypertensive rats

Abstract

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.

Antithrombotic Effect of Captopril and Losartan Is Mediated by Angiotensin-(1-7)

“…Our recent study has shown that during AT 1 receptor blockade, the antithrombotic effect of LOS, at least partly, was related to excessive AT 2 receptor stimulation. 51 Therefore, AT 2 receptor stimulation may explain its incomplete reversal after the administration of Ang-(1-7) receptor blocker. Additionally, LOS is a weak antagonist of thromboxane A 2 /prostaglandin H 2 (TXA 2 /PGH 2 ) receptor on platelets.…”

The Effects of Losartan Compared to Atenolol on Stroke in Patients With Isolated Systolic Hypertension and Left Ventricular Hypertrophy. The LIFE Study

“…Antithrombotic [26][27][28] and improvement of arterial stiffness 29 benefits of treatment with losartan have been described, and may play a role in the beneficial effect of losartan on stroke. 30,31 Angiotensin II type 2-receptor-mediated brainanti-ischemic mechanisms have been proposed that might explain the possible superiority of angiotensin receptor blockers over angiotensin-converting enzyme inhibitors for prevention of stroke.…”

Correcting the imbalanced protective RAS in COVID-19 with angiotensin AT2-receptor agonists

“…Finally, a few studies have suggested that the AT 2 R has anti-thrombotic effects, which could help to counteract the pro-coagulant state in COVID-19. Chabielska et al described that the AT 1 R-blocker Losartan significantly reduced thrombus weight in a model of vena cava thrombosis in Wistar rats with two-kidney, one-clip induced renal hypertension [138]. The effect of Losartan was blocked by the AT 2 R-antagonist PD123319 indicating that indirect AT 2 R-stimulation by elevated levels of Ang II acting on the unopposed AT 2 R was the underlying mechanism of the Losartan effect.…”