Aspirin modifies nitric oxide synthase activity in platelets: effects of acute versus chronic aspirin treatment.
OBJECTIVE
We examined the effects of aspirin on basal and beta-adrenoceptor (beta-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 beta-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/10(8) platelets (P<0.01). Isoproterenol at 1 micromol/l increased platelet NOS activity before but not following intravenous aspirin. After short-term in vitro treatment with aspirin 10 micromol/l, 400 micromol/l or 4 mmol/l, basal platelet L-[3H]citrulline increased similarly, an effect not seen with indomethacin 100 micromol/l or ibuprofen 10 micromol/l. Platelet NOS activity was not increased by albuterol 1 micromol/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 beta-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 beta-adrenergic NOS activation by a COX-dependent mechanism. This indicates that aspirin exerts divergent effects on basal and beta-AR-stimulated platelet NOS activity, which are likely to be of clinical relevance.
O'Kane
Peter D
PD
Department of Cardiology, Cardiothoracic Centre, St Thomas' Hospital, London, UK.
Queen
Lindsay R
LR
Ji
Yong
Y
Reebye
Vikash
V
Stratton
Paula
P
Jackson
Graham
G
Ferro
Albert
A
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000328:Adult; D000420:Albuterol / Q000494:pharmacology; D000704:Analysis of Variance; D001241:Aspirin / Q000008:administration & dosage* / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology*; D002956:Citrulline / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D019323:omega-N-Methylarginine / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D016861:Cyclooxygenase Inhibitors; D010975:Platelet Aggregation Inhibitors; D019323:omega-N-Methylarginine; D002956:Citrulline; D019001:Nitric Oxide Synthase; D007545:Isoproterenol; D000420:Albuterol; D001241:Aspirin; D007213:Indomethacin