title: Influence of nitric oxide on the in vitro antiaggregant effect of ticlopidine.
abstract: The aim of this study was to evaluate the influence of leukocyte nitric oxide (NO) production on the antiplatelet aggregant effect of aspirin and ticlopidine. This in vitro study was done with platelets (platelet-rich plasma, PRP) and polymorphonuclear leukocytes (PMNLs) separated from samples of human blood. Collagen-induced platelet aggregation and calcium-dependent NO production by PMNL were quantified. The inhibition of NO production in PRP significantly reduced the antiaggregant affect of aspirin (IC50 2.64-fold greater), whereas it had no significant effect on the effect of ticlopidine (IC50 1.03-fold greater). Incubating PMNL in PRP increased the antiaggregant effect of both aspirin (IC50 5.09-fold lower) and ticlopidine (IC50 10.16-fold lower). The inhibition of NO production in PMNL significantly reduced the antiaggregant effect of both aspirin (IC50 2.21-fold greater) and ticlopidine (IC50 3.26-fold greater). Both drugs increased leukocyte NO production. The concentration of aspirin that raised NO production by 50% was greater than 1000 microM, whereas the concentration of ticlopidine that led to this effect was 9.14 +/- 0.87 microM. We conclude that the effect of ticlopidine on leukocyte NO production may constitute an addition mechanism to the IIb/IIIa glycoprotein complex inactivation in the inhibition of platelet activation.
authors.affiliation: Department of Pharmacology and Therapetics, School of Medicine, University of Málaga, Campus de Teatinos s/n, Málaga 29071, Spain. jpcruz@uma.es
authors.forename: J P
authors.initials: JP
authors.lastname: De La Cruz
authors.forename: M M
authors.initials: MM
authors.lastname: Arrebola
authors.forename: A
authors.initials: A
authors.lastname: Guerrero
authors.forename: F
authors.initials: F
authors.lastname: Sánchez de la Cuesta
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001241:Aspirin / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013988:Ticlopidine / Q000494:pharmacology*
chemical_list: D010975:Platelet Aggregation Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D013988:Ticlopidine; D001241:Aspirin; D019331:NG-Nitroarginine Methyl Ester