title: TRPA1 activation leads to neurogenic vasodilatation: involvement of reactive oxygen nitrogen species in addition to CGRP and NO.
abstract: Transient receptor potential ankyrin-1 (TRPA1) activation is known to mediate neurogenic vasodilatation. We investigated the mechanisms involved in TRPA1-mediated peripheral vasodilatation in vivo using the TRPA1 agonist cinnamaldehyde.
  
  
  
  Changes in vascular ear blood flow were measured in anaesthetized mice using laser Doppler flowmetry.
  
  
  
  Topical application of cinnamaldehyde to the mouse ear caused a significant increase in blood flow in the skin of anaesthetized wild-type (WT) mice but not in TRPA1 knockout (KO) mice. Cinnamaldehyde-induced vasodilatation was inhibited by the pharmacological blockade of the potent microvascular vasodilator neuropeptide CGRP and neuronal NOS-derived NO pathways. Cinnamaldehyde-mediated 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-mediated response. Co-treatment with a non-selective NOS inhibitor L-NAME and antioxidant apocynin further inhibited the TRPA1-mediated 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.
  
  
  
  This study provides in vivo evidence that TRPA1-induced vasodilatation mediated by cinnamaldehyde requires neuronal NOS-derived 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-mediated vasodilatation may be important in understanding the role of TRPA1 in pathophysiological situations.
authors.affiliation: Cardiovascular Division, BHF Centre of Excellence, King's College London, London, UK.
authors.forename: Aisah A
authors.initials: AA
authors.lastname: Aubdool
authors.affiliation: Cardiovascular Division, BHF Centre of Excellence, King's College London, London, UK.
authors.forename: Xenia
authors.initials: X
authors.lastname: Kodji
authors.affiliation: Cardiovascular Division, BHF Centre of Excellence, King's College London, London, UK.
authors.forename: Nayaab
authors.initials: N
authors.lastname: Abdul-Kader
authors.affiliation: Cardiovascular Division, BHF Centre of Excellence, King's College London, London, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Heads
authors.affiliation: Cardiovascular Division, BHF Centre of Excellence, King's College London, London, UK.|Programa de Pós-graduação, Universidade CEUMA, São Luís, MA, Brazil.
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Fernandes
authors.affiliation: Wolfson Centre for Age Related Diseases, King's College London, London, UK.
authors.forename: Stuart
authors.initials: S
authors.lastname: Bevan
authors.affiliation: Cardiovascular Division, BHF Centre of Excellence, King's College London, London, UK.
authors.forename: Susan D
authors.initials: SD
authors.lastname: Brain
mesh_terms: D000171:Acrolein / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055495:Neurogenesis / Q000187:drug effects; D009589:Nitrogen Oxides / Q000378:metabolism*; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000172:deficiency / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects
chemical_list: D009589:Nitrogen Oxides; D026361:Reactive Nitrogen Species; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D000171:Acrolein; D015740:Calcitonin Gene-Related Peptide; C012843:cinnamaldehyde