Ticlopidine increases nitric oxide generation in heart-transplant recipients: a possible novel property of ticlopidine.
The objective of this study was to evaluate the effects of ticlopidine on the generation of eicosanoids and nitric oxide in heart-transplant recipients. In a randomized double-blind study, we studied the urinary excretion of the stable metabolites of thromboxane, prostacyclin, and nitric oxide before and after ticlopidine (250 mg/day). Platelet aggregation was significantly reduced in ticlopidine-treated patients [from 40.2 +/- 24.2% of maximal aggregation to 14.7 +/- 8.2% in response to adenosine diphosphate (ADP); p < 0.001] but not in the placebo group, confirming the efficacy of the drug with that dosage in these specific patients. The 24-h urinary excretion of prostacyclin metabolites was not modified by ticlopidine (1,865 +/- 833 ng/24 h at day 14 and 1,664 +/- 425 ng/24 h at day 0), whereas the excretion of thromboxane B2 tended to increase in the ticlopidine group (from 3,854 +/- 1,163 ng/24 h at day 0 to 5,014 +/- 2,914 ng/24 h at day 14), although not significantly. The excretion of nitric oxide metabolites (although not different from that of healthy nonimmunosuppressed subjects) was significantly (p < 0.005) increased in the ticlopidine group (from 3,082 +/- 1,683 micromol/24 h at day 0 to 4,133 +/- 2,262 micromol/24 h at day 14), but not in controls. Thus ticlopidine does not reduce prostacyclin but increases the systemic generation of nitric oxide, both substances having major antiplatelet and vasodilator properties. Further studies are warranted to examine whether ticlopidine could reduce the incidence of thromboembolic complications in these patients and whether this possible novel property of ticlopidine is restricted to immunosuppressed heart-transplant recipients.
de Lorgeril
M
M
Laboratoire de Physiologie and GIP-Exercice, Faculté de Médecine J. Lisfranc and CHU de Saint-Etienne, France.
Bordet
J C
JC
Salen
P
P
Durbin
S
S
Defreyn
G
G
Delaye
J
J
Boissonnat
P
P
D000704:Analysis of Variance; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D011464:Epoprostenol / Q000652:urine; D016027:Heart Transplantation; D006801:Humans; D007165:Immunosuppression Therapy; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism* / Q000652:urine; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013931:Thromboxanes / Q000652:urine; D013988:Ticlopidine / Q000494:pharmacology*
D010975:Platelet Aggregation Inhibitors; D013931:Thromboxanes; D009569:Nitric Oxide; D011464:Epoprostenol; D013988:Ticlopidine