title: Differences in the influence of the interaction between acetylsalicylic acid and salicylic acid on platelet function in whole blood and isolated platelets: influence of neutrophils.
abstract: The aim of this study was to characterize the influence of the interaction between acetylsalicylic acid (ASA) and salicylic acid (SA) on the inhibition by ASA of platelet aggregation in platelets isolated from whole blood, and to determine whether leukocytes influence this pharmacological interaction. This in vitro study was done in human blood from which we prepared samples of whole blood, platelet-rich plasma (PRP), PRP plus mononuclear leukocytes, and PRP plus neutrophils. The variables recorded were maximum platelet aggregation intensity, thromboxane B2 (TxB2) production, and nitric oxide (NO) production (N=10 different samples in each type of experiment). Different concentrations of ASA and SA were incubated with all samples. In PRP, the concentration of ASA that inhibited maximum aggregation by 50% (IC50) (281+/-16microM) increased with increasing SA concentration to a maximum of more than 2mM when 500microM SA was used. In whole blood, the IC50 for ASA (24.9+/-1.2microM) decreased with decreasing SA concentrations to 7.9+/-0.8microM with 50microM SA and 15.6+/-0.9microM with 125microM SA, and increased to 46.2+/-2.6microM with 250microM SA and 96.3+/-7.2microM with 500microM SA. In experiments with PRP+neutrophils the IC50 of ASA increased in the presence of all concentrations of SA. The antagonistic interactions were also reflected in the changes in TxB2 production in all samples. In samples of neutrophils incubated with ASA, the curve for NO production was shifted to the right, a finding that paralleled the changes in platelet aggregation. In conclusion, the influence of the interaction between ASA and its metabolite SA on platelet aggregation difference depending on the type of sample, and was antagonistic in PRP but partially agonistic in whole blood. Nitric oxide synthesis showed an additive effect of the two compounds.
authors.affiliation: Department of Pharmacology and Therapeutics, School of Medicine, University of Málaga, Campus de Teatinos s/n, 29071 Málaga, Spain.
authors.forename: J A
authors.initials: JA
authors.lastname: González-Correa
authors.forename: J
authors.initials: J
authors.lastname: Muñoz-Marín
authors.forename: J A
authors.initials: JA
authors.lastname: López-Villodres
authors.forename: M D
authors.initials: MD
authors.lastname: Navas
authors.forename: A
authors.initials: A
authors.lastname: Guerrero
authors.forename: J A
authors.initials: JA
authors.lastname: Torres
authors.forename: J P
authors.initials: JP
authors.lastname: De La Cruz
mesh_terms: D000328:Adult; D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010979:Platelet Function Tests; D020156:Salicylic Acid / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000378:metabolism
chemical_list: D010975:Platelet Aggregation Inhibitors; D009569:Nitric Oxide; D013929:Thromboxane B2; D020156:Salicylic Acid; D001241:Aspirin