© 2003 by European Society of Cardiology
Copyright © 2003, European Society of Cardiology
Aspirin modifies nitric oxide synthase activity in platelets: effects of acute versus chronic aspirin treatment
aDepartment of Cardiology, Cardiothoracic Centre, St Thomas’ Hospital, London, UK
bDepartment of Clinical Pharmacology, Centre for Cardiovascular Biology and Medicine, King's College London, St Thomas’ Hospital, Lambeth Palace Road, London SE1 7EH, UK
* Corresponding author. Tel.: +44-20-7928-9292x2350; fax: +44-20-7401-2242. albert.ferro{at}kcl.ac.uk
Objective: We examined the effects of aspirin on basal and β-adrenoceptor (β-AR)-mediated nitric oxide synthase (NOS) activity in normal platelets. Methods: NOS activity was determined from the conversion of L-[3H]arginine to L-[3H]citrulline, both basally and following β-AR stimulation, in platelets from healthy human subjects following both short- and long-term aspirin administration. Results: Basal L-[3H]citrulline increased following aspirin 800 mg administered intravenously in vivo, from 0.31±0.12 to 0.76±0.14 pmol/108 platelets (P<0.01). Isoproterenol at 1 µmol/l increased platelet NOS activity before but not following intravenous aspirin. After short-term in vitro treatment with aspirin 10 µmol/l, 400 µmol/l or 4 mmol/l, basal platelet L-[3H]citrulline increased similarly, an effect not seen with indomethacin 100 µmol/l or ibuprofen 10 µmol/l. Platelet NOS activity was not increased by albuterol 1 µmol/l, in the presence of indomethacin, ibuprofen or aspirin in vitro. By contrast, oral aspirin 75 mg daily for 14 days did not affect basal platelet NOS activity, but abolished β-adrenergic NOS activation. Conclusions: Aspirin activates basal platelet NOS acutely, but not chronically, through a mechanism independent of cyclooxygenase (COX) inhibition. By contrast, both short- and long-term aspirin treatment inhibit platelet β-adrenergic NOS activation by a COX-dependent mechanism. This indicates that aspirin exerts divergent effects on basal and β-AR-stimulated platelet NOS activity, which are likely to be of clinical relevance.
KEYWORDS Adrenergic; Anticoagulants; Nitric oxide; Platelets; Vasoactive agents
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