Aspirin induces nitric oxide release from vascular endothelium: A novel mechanism of action

D. Taubert, R. Berkels, N. Grosser, H. Schröder, D. Gründemann, E. Schömig

Research output: Contribution to journalArticlepeer-review

118 Scopus citations

Abstract

1 The study was designed to test the hypothesis that aspirin may stimulate nitric oxide (NO) release from vascular endothelium, a pivotal factor for maintenance of vascular homeostasis. 2 Clinical evidence suggests that low-dose aspirin may improve vascular endothelial function. Since other cyclooxygenase (COX) inhibitors showed no beneficial vascular effects, aspirin may exhibit a vasculoprotective, COX-independent mechanism. 3 Luminal NO release was monitored in real time on dissected porcine coronary arteries (PCA) by an amperometric, NO-selective sensor. Additionally, endothelial NO synthase (eNOS) activity was measured in EA.hy 926 cell homogenates by an L-[ 3H]citrulline/L- [ 3H]arginine conversion assay. Superoxide scavenging capacity was assessed by lucigenin-enhanced luminescence. 4 Aspirin induced an immediate concentration-dependent NO release from PCA with an EC 50 of 50 nM and potentiated the NO stimulation by the receptor-dependent agonist substance P. These effects were independent of an increase in intracellular calcium and could be mimicked by stimulation with acetylating aspirin derivatives. The aspirin metabolite salicylic acid or the reversible cyclooxygenase inhibitor indomethacin failed to modulate NO release. Incubation of soluble eNOS for 15 min with 100 μM aspirin or acetylating aspirin analogues increased the L-[ 3H]citrulline yield by 40-80%, while salicylic acid had no effect. Aspirin and salicylic acid showed a similar, but only modest, magnitude and velocity of superoxide scavenging. 5 Our findings demonstrate that therapeutically relevant concentrations of aspirin elicit NO release from vascular endothelium. This effect appears to be due to a direct acetylation of the eNOS protein, but is independent of COX inhibition or inhibition of superoxide-mediated NO degradation.

Original languageEnglish (US)
Pages (from-to)159-165
Number of pages7
JournalBritish Journal of Pharmacology
Volume143
Issue number1
DOIs
StatePublished - Sep 2004

Keywords

  • Aspirin
  • Endothelium
  • Nitric oxide

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