The acute prothrombotic effect of aldosterone in rats is partially mediated via angiotensin II receptor type 1

- The mechanism of aldosterone prothrombotic action is partially mediated via AT1.
- AT1 blockade reduces the harmful effects of aldosterone in hemostasis.
- Not only MR but also AT1 activation is essential for aldosterone action.

IntroductionWe showed previously that the prothrombotic effect of one hour aldosterone (ALDO) infusion in rats was only partially mediated by the mineralocorticoid receptor (MR). Bearing in mind that ALDO potentiates the effects of angiotensin II (Ang II), in the present study we investigated the role of Ang II receptor type 1 - AT1 in acute ALDO prothrombotic action.Materials and methodsThe experiments were performed in a stasis-induced venous thrombosis model in male Wistar, normotensive rats. ALDO (30 μg/kg) was infused for 1 h. Valsartan (VAL; 10 mg/kg), a selective AT1 receptor antagonist, was administered in a single bolus injection before ALDO infusion. Eplerenone (EPL, 100 mg/kg), a selective MR receptor antagonist, was administered per os before ALDO. Thrombus weight and incidences of thrombosis were assayed. Bleeding time and platelet adhesion to collagen were evaluated as primary hemostasis parameters. The plasma levels of some coagulation and fibrinolysis parameters, and plasma NO metabolite levels were assayed.ResultsAT1 blockade with valsartan significantly reduced ALDO-induced thrombosis expressed as a reduced thrombus mass (p < 0.05 vs ALDO) and diminished the incidence of thrombosis. Valsartan reduced the ALDO-induced changes in bleeding time and platelet adhesion, as well as in coagulation, fibrinolysis, and NO metabolite levels. The effect of AT1 blockade in ALDO-induced thrombosis was similar to the effect of MR blockade. However, dual blockade of AT1 and MR showed no additional benefit.ConclusionsALDO prothrombotic action is partially mediated via AT1 receptor in the mechanism involving enhanced platelet activation, induced coagulation, impaired fibrinolysis and reduced NO bioavailability.