Effect of losartan on human platelets activation by thromboxane A(2)

Background and aim. Previous studies have demonstrated that losartan, an AT -1 receptor antagonist of angiotensin II (Ang II) could block the receptor of thromboxane A(2) (TXA(2)) in the vascular wall. The aim of the present s tudy was to assess the effect of losartan on human platelet activation. Material and methods. Platelets were obtained from 15 healthy men between t he age 26 and 40. Platelet activation was measured by changes in the light transmission of platelet-rich plasma stimulated by a synthetic TXA(2) analo gue, U46619 (5 x 10(-6) mol/l). Results. The U46619-stimulated platelet aggregation was significantly inhib ited by losartan in a dose-response manner. Only a high dose of EXP 3174 (5 x 10(-5) mol/l), the in vivo active metabolite of losartan, was able to at tenuate U46619-induced platelet activation. Captopril, an angiotensin I-con verting inhibitor failed to modify U46619-induced platelet aggregation. Des pite the platelets expressing AT-1 type receptors, of Ang II exogenous Ang II did not modify platelet aggregation induced by U46619. The binding of U4 6619 to platelets was competitively inhibited by losartan in dose-dependent manner. However, only a high dose of EXP 3174 reduced the binding of U4661 9. Captopril failed to modify the binding of U46619 to platelets. Conclusions. Losartan decreased platelet aggregation by a TXA(2)-dependent mechanism. EXP 3174 showed a lesser potency than losartan to reduce TXA(2)- platelet activation. Captopril and exogenous angiotensin II had no effect o n human platelet activation. These results suggest that losartan reduced TX A(2)-dependent platelet activation independently of the blockade of AT-1 re ceptors.