{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T10:58:52Z","timestamp":1777633132036,"version":"3.51.4"},"reference-count":65,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2016,6,21]],"date-time":"2016-06-21T00:00:00Z","timestamp":1466467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Transient receptor potential ankyrin\u20101 (TRPA1) activation is known to mediate neurogenic vasodilatation. We investigated the mechanisms involved in TRPA1\u2010mediated peripheral vasodilatation <jats:italic>in vivo<\/jats:italic> using the TRPA1 agonist cinnamaldehyde.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Changes in vascular ear blood flow were measured in anaesthetized mice using laser Doppler flowmetry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Topical application of cinnamaldehyde to the mouse ear caused a significant increase in blood flow in the skin of anaesthetized wild\u2010type (WT) mice but not in TRPA1 knockout (KO) mice. Cinnamaldehyde\u2010induced vasodilatation was inhibited by the pharmacological blockade of the potent microvascular vasodilator neuropeptide CGRP and neuronal NOS\u2010derived NO pathways. Cinnamaldehyde\u2010mediated vasodilatation was significantly reduced by treatment with reactive oxygen nitrogen species (RONS) scavenger such as catalase and the SOD mimetic TEMPOL, supporting a role of RONS in the downstream vasodilator TRPA1\u2010mediated response. Co\u2010treatment with a non\u2010selective NOS inhibitor L\u2010NAME and antioxidant apocynin further inhibited the TRPA1\u2010mediated vasodilatation. Cinnamaldehyde treatment induced the generation of peroxynitrite that was blocked by the peroxynitrite scavenger FeTPPS and shown to be dependent on TRPA1, as reflected by an increase in protein tyrosine nitration in the skin of WT, but not in TRPA1 KO mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>This study provides <jats:italic>in vivo<\/jats:italic> evidence that TRPA1\u2010induced vasodilatation mediated by cinnamaldehyde requires neuronal NOS\u2010derived NO, in addition to the traditional neuropeptide component. A novel role of peroxynitrite is revealed, which is generated downstream of TRPA1 activation by cinnamaldehyde. This mechanistic pathway underlying TRPA1\u2010mediated vasodilatation may be important in understanding the role of TRPA1 in pathophysiological situations.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13519","type":"journal-article","created":{"date-parts":[[2016,5,18]],"date-time":"2016-05-18T02:32:15Z","timestamp":1463538735000},"page":"2419-2433","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":81,"title":["TRPA1 activation leads to neurogenic vasodilatation: involvement of reactive oxygen nitrogen species in addition to CGRP and NO"],"prefix":"10.1111","volume":"173","author":[{"given":"Aisah A","family":"Aubdool","sequence":"first","affiliation":[{"name":"Cardiovascular Division, BHF Centre of Excellence King's College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xenia","family":"Kodji","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, BHF Centre of Excellence King's College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nayaab","family":"Abdul\u2010Kader","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, BHF Centre of Excellence King's College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Heads","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, BHF Centre of Excellence King's College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth S","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, BHF Centre of Excellence King's College London  London UK"},{"name":"Programa de P\u00f3s\u2010gradua\u00e7\u00e3o Universidade CEUMA  S\u00e3o Lu\u00eds MA Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stuart","family":"Bevan","sequence":"additional","affiliation":[{"name":"Wolfson Centre for Age Related Diseases King's College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan D","family":"Brain","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, BHF Centre of Excellence King's College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,6,21]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13348"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13349"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13354"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.644476"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5369-07.2008"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2009.58"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6732"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(04)00150-3"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0505356102"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.4.1620"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2006.04742.x"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-1716.2010.02203.x"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.52"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/313054a0"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1989.tb11923.x"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1139\/y2012-012"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.288.5464.306"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2011.02.007"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12856"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(97)01320-4"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-200103000-00002"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13164"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.108.189530"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5381"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1993.tb13878.x"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1102147"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.12-221218"},{"key":"e_1_2_12_29_1","doi-asserted-by":"crossref","first-page":"26677","DOI":"10.1016\/S0021-9258(18)47072-X","article-title":"Potent and selective inhibition of human nitric oxide synthases. 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