Effect of triflusal on human platelet aggregation and secretion: Role of nitric oxide

Introduction and aims. The thrombotic process is a multicellular phenomenon in which not only platelets are involved but also neutrophils are involved . Recent in vitro studies performed in our laboratory have demonstrated tha t triflusal reduced platelet aggregation by stimulating nitric oxide (NO) p roduction by neutrophils. The aim of the present study was to evaluate whet her the in vivo treatment with triflusal could also modify the ability of n eutrophils to produce NO. Furthermore, the role of NO released by neutrophi ls on platelet aggregation and secretion was also tested. Methods. The study was performed in 12 healthy volunteers of 32 +/- 6 years of age. The volunteers were treated with triflusal (600 mg/day) for 5 days and platelets and neutrophils were isolated before and after treatment. Th e ability of neutrophils to produce NO and the capacity of inhibiting plate let aggregation and secretion of transforming growth factor-beta (TGF-beta) were assessed. Results. After the treatment with triflusal we obtained the following resul ts: a) an increase in NO production by neutrophils; 6) potentiation of the inhibition of platelet aggregation by neutrophils, an effect that was rever ted by incubating neutrophils with an L-arginine antagonist, L-NAME, and c) the presence of neutrophils reduced the release of TGF-beta by platelets m easured as index of platelet secretion by a NO-independent mechanism. Conclusions. Triflusal (600 mg/day/5 days) stimulated NO production by neut rophils. After the treatment with triflusal, neutrophils inhibited both pla telet aggregation and secretion. The antiaggregating effect of neutrophils was an NO-dependent mechanism while the inhibition of platelet secretion me diated by neutrophils after the treatment with triflusal was an NO-independ ent mechanism.