title: [The effect of triflusal on human platelet aggregation and secretion: the role of nitric oxide].
abstract: OBJECTIVE
  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 that triflusal reduced platelet aggregation by stimulating nitric oxide (NO) production by neutrophils. The aim of the present study was to evaluate whether the in vivo treatment with triflusal could also modify the ability of neutrophils to produce NO. Furthermore, the role of NO released by neutrophils 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. The ability of neutrophils to produce NO and the capacity of inhibiting platelet aggregation and secretion of transforming growth factor-beta (TGF-beta) were assessed.
  
  
  RESULTS
  After the treatment with triflusal we obtained the following results: a) an increase in NO production by neutrophils; b) potentiation of the inhibition of platelet aggregation by neutrophils, an effect that was reverted by incubating neutrophils with an L-arginine antagonist, L-NAME, and c) the presence of neutrophils reduced the release of TGF-beta by platelets measured as index of platelet secretion by a NO-independent mechanism.
  
  
  CONCLUSIONS
  Triflusal (600 mg/day/5 days) stimulated NO production by neutrophils. After the treatment with triflusal, neutrophils inhibited both platelet aggregation and secretion. The antiaggregating effect of neutrophils was an NO-dependent mechanism while the inhibition of platelet secretion mediated by neutrophils after the treatment with triflusal was an NO-independent mechanism.
authors.affiliation: Laboratorio de Investigación Cardiovascular, Fundación Jiménez Díaz, Madrid.
authors.forename: L
authors.initials: L
authors.lastname: Sánchez de Miguel
authors.forename: M
authors.initials: M
authors.lastname: Montón
authors.forename: M
authors.initials: M
authors.lastname: Mar Arriero
authors.forename: J I
authors.initials: JI
authors.lastname: Guerra
authors.forename: A
authors.initials: A
authors.lastname: Jiménez
authors.forename: F
authors.initials: F
authors.lastname: González-Fernández
authors.forename: M
authors.initials: M
authors.lastname: García-Durán
authors.forename: T
authors.initials: T
authors.lastname: Bellver
authors.forename: L
authors.initials: L
authors.lastname: Rico
authors.forename: J
authors.initials: J
authors.lastname: Romero
authors.forename: J
authors.initials: J
authors.lastname: Gómez
authors.forename: A
authors.initials: A
authors.lastname: Núñez
authors.forename: P
authors.initials: P
authors.lastname: Marcos
authors.forename: R
authors.initials: R
authors.lastname: Ayala
authors.forename: J
authors.initials: J
authors.lastname: Farré
authors.forename: S
authors.initials: S
authors.lastname: Casado
authors.forename: A
authors.initials: A
authors.lastname: López-Farré
mesh_terms: D000328:Adult; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism*; D002956:Citrulline / Q000097:blood / Q000187:drug effects; D006152:Cyclic GMP / Q000097:blood / Q000494:pharmacology; D006157:Guanosine Monophosphate / Q000097:blood; D006801:Humans; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D012459:Salicylates / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000097:blood / Q000187:drug effects
chemical_list: D010975:Platelet Aggregation Inhibitors; D012459:Salicylates; D016212:Transforming Growth Factor beta; C016167:triflusal; D002956:Citrulline; D009569:Nitric Oxide; D006157:Guanosine Monophosphate; D006152:Cyclic GMP