Inhibition of platelet activation in stroke-prone spontaneously hypertensive rats: Comparison of losartan, candesartan, and valsartan

In vitro studies have suggested that losartan interacts with the thromboxan e (TxA(2))/ prostaglandin H-2 (PGH(2)) receptor in human platelets, reducin g TxA(2)-dependent platelet activation. The aim of this study was to evalua te the effect of different angiotensin II type 1 receptor antagonists in st roke-prone spontaneously hypertensive rats (SHRSP). The level of platelet a ctivation was assessed by determining P-selectin expression in platelets by flow cytometry. The ex vivo adhesion of platelets was also analyzed. The n umber of platelets that expressed P-selectin in SPSHR was significantly inc reased (% P-selectin expression: WKY 4 +/- 0, 4%; SHRSP 15.5 +/- 0, 8% [n = 8], p < 0.05). In SHRSP receiving losartan (20 mg/kg body weight per day) the percentage of platelets expressing P-selectin fell to levels close to t hat observed in WKY. The number of platelets from SHRSP treated with valsar tan and candesartan (20 mg/kg body weight per day for 14 days) that express ed P-selectin was not significantly different from those from untreated SPR HR. Only losartan treatment reduced ex vivo platelet adhesion to a syntheti c surface. The antiplatelet effect of losartan does not appear to be relate d to the level of blood pressure reduction. In ex vivo experiments, losarta n significantly reduced the binding of the radiolabeled TxA(2) agonist U466 19 to platelets obtained from SHRSP in a dose-dependent manner. Treatment w ith losartan reduced the number of activated platelets in SHRSP independent ly of its blood pressure effects. TxA(2)-receptor blockade is proposed as a mechanism by which losartan can prevent platelet activation.