Modulation of human platelet aggregation by the phosphodiesterase type 5 inhibitor sildenafil

The aim of this study was to investigate if the phospodiesterase type 5 inh ibitor sildenafil inhibits collagen- or ADP-induced:human platelet aggregat ion and bleeding time. To investigate this, two studies were designed. In t he first, a single oral dose of sildenafil, 100 mg, was administered to hea lthy men. Bleeding time was determined and agonist (ADP and collagen)induce d platelet aggregation (ex vivo in platelet rich plasma) was measured 0, 1, and 4 h after application. In the second, a single oral dose of sildenafil , 50 mg, was administered and, in addition to the parameters in the first s tudy, we also determined the platelet aggregation after 24 h and measured t he effect of a nitric oxide donor (S-nitroso-N-acetylpenicillamine [SNAP]) in combination to mimic a physiologic nitric oxide release from the endothe lium. The bleeding time of 1 h after sildenafil medication (100 mg) was sig nificantly prolonged but recovered toward control values after 4 h, whereas application of sildenafil at a lower dose (50 mg) did not alter the bleedi ng time. Sildenafil (100 and 50 mg) did not inhibit the ADP-induced aggrega tion, whereas the collagen-induced aggregation (100 mg) was markedly reduce d after I h and significantly inhibited 4 h after application. This inhibit ory effect was overcome by higher concentrations of collagen. SNAP (0.5 muM ) induced an inhibition of platelet aggregation that was potentiated after taking sildenafil (50 mg, 1 and 4 h afterward) and abrogated after 24 h. Th ese data indicates that sildenafil may inhibit collagen-induced platelet ag gregation ex vivo. After co-administration of nitric oxide, collagen- and A DP-induced platelet aggregation was significantly inhibited, which may refl ect physiologic conditions of an in vivo system.