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

A recent study has shown that losartan, an AT 1 -receptor antagonist, interacts with thromboxane A 2 (TxA 2 )/prostaglandin H 2 (PGH 2 ) receptors in human platelets. The aim of the present study was to analyse the ability of different angiotensin II (Ang II) AT 1 -receptor antagonists to inhibit TxA 2 -dependent human platelet activation. Platelets were obtained from healthy volunteers and were stimulated with the thromboxane A 2 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 [ 3 H]-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 AT 1 -receptor antagonists reduce TxA 2 -dependent human platelet activation, it is not a feature common to all AT 1 antagonists.