Effect of organic nitrates on ex vivo platelet aggregation and fibrinolysis in man.
Previous in vitro studies have suggested that nitric oxide-releasing agents can increase the fibrinolytic capacity while platelet aggregability is decreased. We have therefore directly compared the influence of organic nitrates on ex vivo platelet aggregation and the fibrinolytic system in 16 healthy volunteers. Each subject received glyceryl trinitrate (GTN, 2 x 32 mg patches), isosorbide-dinitrate (ISDN, 120 mg p.o.), isosorbide-5-mononitrate (ISMN, 50 mg p.o.), and placebo in a randomized double-blind manner. Ex vivo platelet aggregation, activities and concentrations of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) were measured before, 90 and 150 minutes after drug intake. GTN, ISDN, and ISMN were equipotent in respect to their hemodynamic responses. Platelet aggregation induced with a low (1 microM) but not with a high (4 microM) agonist concentration (adenosine diphosphate, ADP) was reduced after GTN and ISDN. ISMN had no influence on aggregation. An increase of t-PA activity was significantly reduced after GTN and ISDN (p<0.05), whereas t-PA concentrations were not affected by the nitrates. A decrease of PAI-1 activity after ISMN and placebo was not apparent after GTN and ISDN. In the case of GTN, the decrease of PAI-1 concentration was delayed. In conclusion, GTN and ISDN did not increase the fibrinolytic capacity but decreased the reversible phase of ADP-induced platelet aggregation, while ISMN had neither an effect on the fibrinolytic system nor on platelet aggregation.
Wolfram
G
G
DLR Institute of Aerospace Medicine, Linder H-ohe, K-oln, D-51147 Germany.
Meyer
U
U
Scheske
U
U
Horn
M
M
Drummer
C
C
Spannagl
M
M
Gerzer
R
R
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005342:Fibrinolysis / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007548:Isosorbide Dinitrate / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D005996:Nitroglycerin / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D012016:Reference Values; D010959:Tissue Plasminogen Activator / Q000097:blood; D014665:Vasodilator Agents / Q000494:pharmacology*
D017395:Plasminogen Activator Inhibitor 1; D010975:Platelet Aggregation Inhibitors; D014665:Vasodilator Agents; D000244:Adenosine Diphosphate; D010959:Tissue Plasminogen Activator; D005996:Nitroglycerin; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate