Effect of losartan on human platelet activation

Objective Previous studies have demonstrated that losartan can block the th romboxane A(2) receptor on the vascular wall. The aim of the present study was to assess the effect of losartan on human platelet activation. Methods Platelets were obtained from 15 healthy men, aged 26-40 years. Plat elet activation was measured by changes in the light transmission of platel et-rich plasma stimulated by the thromboxane A(2) analog U46619 (5 x 10(-6) mol/l) or ADP (10(-5) mol/l). Results U46619-stimulated platelet aggregation was significantly inhibited by losartan in a dose-dependent manner. Only a high dose of EXP 3174 (5 x 1 0(-5) mol/l), the in vivo active metabolite of losartan, was able to attenu ate U46619-induced platelet activation. Captopril, an angiotensin I convert ing inhibitor, failed to modify U46619-induced platelet aggregation. Furthe rmore, the binding of [H-3]-U46619 to platelets was competitively inhibited by losartan, whereas only a high dose of EXP 3174 reduced the binding of [ H-3]-U46619. Captopril failed to modify the binding of [H-3]-U46619 to plat elets. Losartan also reduced the platelet activation induced by ADP (10(-5) mol/l), a platelet agonist partially dependent on thromboxane A(2). In add ition, when thromboxane A(2) generation was blocked by aspirin, ADP-induced platelet aggregation was inhibited to a similar degree to the inhibition i nduced by losartan. Exogenous angiotensin II did not elicit any modificatio n of either U46619- or ADP-stimulated platelet aggregation. Conclusions Losartan decreased platelet aggregation by a thromboxane A(2)-d ependent mechanism. EXP 3174 was less potent than losartan in reducing thro mboxane A(2)-dependent platelet activation. Captopril and exogenous angiote nsin II had no effect on human platelet activation. These results suggest t hat losartan reduced thromboxane A(2)-dependent platelet activation indepen dently of its effect on angiotensin II. J Hypertens 1999, 17:447-452 (C) Li ppincott Williams & Wilkins.