{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:32:53Z","timestamp":1791196373565,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2009,2,17]],"date-time":"2009-02-17T00:00:00Z","timestamp":1234828800000},"content-version":"vor","delay-in-days":1630,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2004,9]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>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.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Clinical evidence suggests that low\u2010dose aspirin may improve vascular endothelial function. Since other cyclooxygenase (COX) inhibitors showed no beneficial vascular effects, aspirin may exhibit a vasculoprotective, COX\u2010independent mechanism.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Luminal NO release was monitored in real time on dissected porcine coronary arteries (PCA) by an amperometric, NO\u2010selective sensor. Additionally, endothelial NO synthase (eNOS) activity was measured in EA.hy 926 cell homogenates by an <jats:sc>L<\/jats:sc>\u2010[<jats:sup>3<\/jats:sup>H]citrulline\/<jats:sc>L<\/jats:sc>\u2010[<jats:sup>3<\/jats:sup>H]arginine conversion assay. Superoxide scavenging capacity was assessed by lucigenin\u2010enhanced luminescence.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Aspirin induced an immediate concentration\u2010dependent NO release from PCA with an EC<jats:sub>50<\/jats:sub> of 50 n<jats:sc>M<\/jats:sc> and potentiated the NO stimulation by the receptor\u2010dependent 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 <jats:italic>\u03bc<\/jats:italic><jats:sc>M<\/jats:sc> aspirin or acetylating aspirin analogues increased the <jats:sc>L<\/jats:sc>\u2010[<jats:sup>3<\/jats:sup>H]citrulline yield by 40\u201380%, while salicylic acid had no effect. Aspirin and salicylic acid showed a similar, but only modest, magnitude and velocity of superoxide scavenging.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>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\u2010mediated NO degradation.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p> <jats:italic>British Journal of Pharmacology<\/jats:italic> (2004) <jats:bold>143<\/jats:bold>, 159\u2013165. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0705907\">10.1038\/sj.bjp.0705907<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0705907","type":"journal-article","created":{"date-parts":[[2004,9,2]],"date-time":"2004-09-02T20:31:48Z","timestamp":1094157108000},"page":"159-165","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":134,"title":["Aspirin induces nitric oxide release from vascular endothelium: a novel mechanism of action"],"prefix":"10.1111","volume":"143","author":[{"given":"D","family":"Taubert","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Berkels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"Grosser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Schr\u00f6der","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Gr\u00fcndemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Sch\u00f6mig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,2,17]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(02)01828-9"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.101.10.1206"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1552-4604.1995.tb04044.x"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.37.2.240"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M108789200"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI108068"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.73.5.808"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0049-3848(81)90205-X"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M302238200"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/21224"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.80.12.3734"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2001.280.2.F193"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1537-2995.1981.21181127484.x"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000025404.78001.D8"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-136-2-200201150-00016"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1385\/1-59259-002-0:33"},{"key":"e_1_2_6_18_1","first-page":"313","article-title":"Non\u2010enzymatic acetylation of proteins by aspirin as protection against the secondary complications of diabetes mellitus","volume":"36","author":"HUN\u2010OPFER C.","year":"1986","journal-title":"Acta Physiol. 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