[Inhibitory effect of isosorbide dinitrate on whole blood aggregation]

Isosorbide dinitrate (ISDN) has an inhibitory effect on platelet aggregation through the generation of nitric oxide (NO). We examined the effect of ISDN on whole blood aggregation using an impedance aggregometer. Blood samples were obtained from 16 patients with acute myocardial infarction and 4 patients with angina pectoris before and after an intravenous administration of ISDN during coronary arteriography. Whole blood obtained from normal healthy donors was used for an in vitro study. Whole blood aggregation after administration of ISDN was significantly inhibited compared to that before administration (36.1 +/- 8.3 vs 43.7 +/- 8.4 omega, p < 0.001), and cyclic guanine monophosphate (c-GMP) concentration increased (5.56 +/- 2.0 vs 5.14 +/- 1.86 p mol/ml, p < 0.05). The inhibitory effect of ISDN was also observed in the in vitro study, in which the effective concentration of ISDN corresponded to the blood level of ISDN (> or = 10(-7) mol) in the clinical setting. The inhibitory effect of ISDN was diminished by the addition of methylene blue or NG-monomethyl-L-arginine monoacetate in the exo vivo and in vitro studies. The concentration of c-GMP was increased by the addition of ISDN to platelets and white blood cell suspended plasma compared to the control (1.93 +/- 0.50 vs 1.77 +/- 0.42 p mol/ml, p < 0.05), but there was no significant difference when ISDN was added to platelet-rich plasma. These results suggest that ISDN inhibits whole blood aggregation through NO generation and white blood cells are important in the mechanism of ISDN action.