Comparative Effects of Angiotensin Ii At-1-type Receptor Antagonists In Vitro on Human Platelet Activation

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 this study was to analyze 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. Platelets were stimulated with the TxA 2 analogue, U46619 (10 -6 M). U46619-stimulated platelet activation was significantly reduced by both losartan and irbesartan in a dose-dependent manner. Only maximal doses of valsartan (5 x 10 -6 M) and the main metabolite of losartan, EXP3174 (5 x 10 -6 M), reduced U46619-induced platelet activation. Whereas the active form of candesartan cilexetil (candesartan, CV-11974) failed to modify platelet activation involved by TxA 2 . telmisartan showed a higher effect than valsartan and EXP3174 but lower than either losartan and irbesartan. Losartan or irbesartan reduced the binding of [ 3 H]-U46619 to platelets, an effect that was observed with lower ability with the other AT-I antagonists. Although platelets expressed AT-1-type receptors, exogenous Ang II did not modify platelet activation. This effect was not modified by blocking the AT-2 receptor with PD123319. These results suggest that some AT-1-receptor antagonists reduce TxA 2 -dependent activation independent of Ang II involvement.