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

• Published in: European journal of pharmacology Vol. 397; no. 1; pp. 35 - 41
• Main Authors: De La Cruz, José Pedro, Blanco, Encarnación, Sánchez de la Cuesta, Felipe
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 26-05-2000; Elsevier
• Subjects: Adult; Aspirin; Aspirin - pharmacology; Biological and medical sciences; Blood Platelets - cytology; Blood Platelets - drug effects; Blood. Blood coagulation. Reticuloendothelial system; Cyclic GMP - metabolism; Dipyridamole; Dipyridamole - pharmacology; Dose-Response Relationship, Drug; Humans; Male; Medical sciences; Neutrophils - cytology; Neutrophils - drug effects; Neutrophils - metabolism; Nitric oxide (NO); Nitric Oxide - metabolism; Nitric Oxide - physiology; Pharmacology. Drug treatments; Platelet; Platelet Aggregation - drug effects; Platelet Aggregation Inhibitors - pharmacology; Polymorphonuclear leukocyte; Aspirin; Platelet; Nitric oxide (NO); Dipyridamole; Polymorphonuclear leukocyte; Human; Drug combination; Leukocyte; Interaction; Granulocyte; 3',5'-GMP; Acetylsalicylic acid; In vitro; Antiplatelet agent; Nitric oxide; Neutrophil; Salicylates; Mechanism of action
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(00)00245-4

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 (IC
50) of aspirin was 139±11 μM in platelet-rich plasma, 367±21 μM in platelet-rich plasma+
l-
N
G-nitro-arginine-methyl-ester (
l-NAME), and 42±3 μM in platelet-rich plasma+
l-arginine. The IC
50 for dipyridamole in platelet-rich plasma was not affected by
l-NAME or
l-arginine; the combination of aspirin with 20 μM dipyridamole (which has no effect per se) led to an IC
50 of 51±2 μM in platelet-rich plasma, 101±7 μM in platelet-rich plasma+
l-NAME, and 13±2 μM 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 μM aspirin, 110±9 μM dipyridamole, and 16±2 μM aspirin+dipyridamole. Dipyridamole alone at a concentration of 20 μM 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.