Effect of dipyridamole and aspirin on the platelet-neutrophil interaction via the nitric oxide pathway

This study was designed to determine the influence of the combination of aspirin and dipyridamole on the interaction in vitro between neutrophils and platelets through the nitric oxide (NO) pathway. Collagen-induced platelet aggregation (impedance method) was determined in platelet-rich plasma and in platelet-rich plasma + neutrophils, and cGMP (enzyme immunoanassay) and NO levels (electrochemical method, with a ISO-200 electrode) were also measured. The 50% inhibitory concentration (ICS,) of aspirin was 139 +/- 11 mu M in platelet-rich plasma, 367 +/- 21 mu M in platelet-rich plasma + L-N-G-nitro-arginine-methyl-ester (L-NAME), and 42 +/- 3 mu M in platelet-rich plasma + L-arginine. The IC50 for dipyridamole in platelet-rich plasma was not affected by L-NAME or L-arginine; the combination of aspirin with 20 mu M dipyridamole (which has no effect per se) led to an IC50 of 51 +/- 2 mu M in platelet-rich plasma, 101 +/- 7 mu M in platelet-rich plasma + L-NAME, and 13 +/- 2 mu M in platelet-rich plasma + L-arginine. The cGMP levels showed the greatest increases in the aspirin plus dipyridamole group. Dipyridamole and aspirin increased the leukocyte production of NO: 50% increases were obtained at concentrations of 285 +/- 31 mu M aspirin, 110 +/- 9 mu M dipyridamole, and 16 +/- 2 mu M aspirin + dipyridamole. Dipyridamole alone at a concentration of 20 mu M had no significant effect on NO levels. We conclude that the combination of aspirin and dipyridamole significantly increases the antiplatelet effect of leukocytes, through an increase of NO, and that this effect is further evidence of the therapeutic benefits of this combination of drugs. (C) 2000 Elsevier Science B.V. All rights reserved.