Effect of single oral dose of aspirin on human platelet functions and plasma plasminogen activator inhibitor-1.
Previous reports documented the inhibitory efficacy of different doses of aspirin on arachidonic acid (AA)-induced platelet aggregation, however, the sensitivity of platelets toward other agonists as well as the effects of aspirin on platelet and plasma plasminogen activator inhibitor-1 (PAI-1) release and levels were not investigated. Hence, the present study was undertaken to investigate the effect and duration of action of a single oral dose (650 mg) of aspirin on human platelet functions (n = 34, normal healthy male and female volunteers) including aggregation, fibrinogen binding and PAI-1 release, and on the plasma level of PAI-1. Aspirin demonstrated a rapid onset of action (at 2 h after ingestion) in specifically inhibiting ex vivo AA-mediated functions including (a) fibrinogen binding to gel-purified platelets, (b) platelet aggregation, and (c) platelet PAI-1 release. A peak reduction of plasma PAI-1 level at 2 h was demonstrated as well. The effect of aspirin on the ex vivo AA-mediated effects (a-c) was shown to last for up to 4 days. However, aspirin treatment resulted in a rebound effect in platelet function (a-c) to other platelet agonists such as adenosine diphosphate or the combination of agonists including adenosine diphosphate, epinephrine, and AA. In conclusion, a single oral dose of aspirin has long-acting effects on AA-induced platelet activation and reduces plasma levels of PAI-1 as well.(ABSTRACT TRUNCATED AT 250 WORDS)
Mousa
S A
SA
DuPont Merck Pharmaceutical Company, Cardiovascular Diseases Division, Wilmington, DE 19880-0400.
Forsythe
M S
MS
Bozarth
J M
JM
Reilly
T M
TM
D000244:Adenosine Diphosphate / Q000494:pharmacology; D016718:Arachidonic Acid / Q000494:pharmacology / Q000502:physiology; D001241:Aspirin / Q000008:administration & dosage* / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000378:metabolism*; D010974:Platelet Aggregation / Q000187:drug effects; D013997:Time Factors
D017395:Plasminogen Activator Inhibitor 1; D016718:Arachidonic Acid; D000244:Adenosine Diphosphate; D005340:Fibrinogen; D001241:Aspirin; D004837:Epinephrine