Losartan inhibits in vitro platelet activation: comparison with candesartan and valsartan

Abstract

A recent study has shown that losartan, an AT₁-receptor antagonist, interacts with thromboxane A₂ (TxA₂)/prostaglandin H₂ (PGH₂) receptors in human platelets. The aim of the present study was to analyse the ability of different angiotensin II (Ang II) AT₁-receptor antagonists to inhibit TxA₂-dependent human platelet activation. Platelets were obtained from healthy volunteers and were stimulated with the thromboxane A₂ analogue, U46619 (10^-6 mol/L). U46619-stimulated platelet activation was significantly reduced by losartan in a dose-dependent manner. Only maximal doses of valsartan (5x10^-6 mol/L), reduced U46619-induced platelet activation. The active form of candesartan cilexetil, candesartan (CV-11974), failed to modify platelet activation. Losartan reduced the binding of [³H]-U46619 to platelets, an effect that was observed to a lesser extent with valsartan but not with CV-11974. These results suggest that, whilst some AT₁-receptor antagonists reduce TxA₂-dependent human platelet activation, it is not a feature common to all AT₁ antagonists.