In vivo aspirin supplementation inhibits nitric oxide consumption by human platelets.
Antiplatelet therapies improve endothelial function in atherosclerosis, suggesting that platelets regulate vascular nitric oxide (NO) bioactivity in vivo. Herein, washed platelets consumed NO on activation in an aspirin-sensitive manner, and aspirin enhanced platelet NO responses in vitro. To examine whether in vivo aspirin can inhibit platelet NO consumption, a double-blind placebo-controlled study was conducted. After a 2-week nonsteroidal anti-inflammatory drug (NSAID)-free period, healthy men were randomly assigned and administered aspirin (75 mg/d orally) or identical placebo for 14 days, then crossed over to the opposite arm. Following in vivo aspirin, NO consumption by platelets was inhibited 91%. Rate of onset and recovery following aspirin withdrawal was consistent with cyclooxygenase 1 (COX-1) inhibition. In a small substudy, NO consumption by platelets from postmenopausal women was faster in hypercholesterolemics and less sensitive to aspirin (ie, 39% versus 76% inhibition for hypercholesterolemics or normocholesterolemics, respectively). However, 150 mg aspirin/day increased inhibition of NO consumption by platelets of hypercholesterolemics to 80%. Comparisons of platelet COX-1 or -2 expression and urinary 11-dehydro-thromboxane B2 excretion suggested that aspirin was less able to block platelet activation in vivo in hypercholesterolemia. In conclusion, aspirin inhibits NO consumption by platelets from healthy subjects, but its beneficial effects on NO bioactivity may be compromised in some hypercholesterolemic patients.
Department of Medical Biochemistry and Immunology, University of Wales College of Medicine, Heath Park, Cardiff, CF14 4XN, United Kingdom.
P Claire
PC
Williams
Marcus J
MJ
Coffey
Barbara
B
Coles
Stephanie
S
Sanchez
Jason D
JD
Morrow
John R
JR
Cockcroft
Malcolm J
MJ
Lewis
Valerie B
VB
O'Donnell
D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006262:Health; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D010974:Platelet Aggregation / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D013931:Thromboxanes / Q000652:urine; D013997:Time Factors
D007527:Isoenzymes; D013931:Thromboxanes; D009569:Nitric Oxide; D011451:Prostaglandin-Endoperoxide Synthases; D006152:Cyclic GMP; D001241:Aspirin