Evidence for the pathophysiological relevance of TRPA1 receptors in the cardiovascular system in vivo.
OBJECTIVE
The aim of the study is to investigate transient receptor potential ankyrin 1 (TRPA1)-induced responses in the vasculature and on blood pressure and heart rate (HR), in response to TRPA1 agonists using wild-type (WT) and TRPA1 knockout (KO) mice.


RESULTS
TRPA1 agonists allyl isothiocyanate and cinnamaldehyde (CA) significantly increased blood flow in the skin of anaesthetized WT, but not in TRPA1 KO mice. CA also induced TRPA1-dependent relaxation of mesenteric arteries. Intravenously injected CA induced a transient hypotensive response accompanied by decreased HR that was, depending on genotype and dose, followed by a more sustained dose-dependent pressor response (10-320 micromol/kg). CA (80 micromol/kg) induced a depressor response that was significantly less in TRPA1 KO mice, with minimal pressor effects. The pressor response of a higher CA dose (320 micromol/kg) was observed in WT but not in TRPA1 KO mice, indicating involvement of TRPA1. Experiments using TRP vanilloid 1 (TRPV1) KO and calcitonin gene-related peptide (CGRP) KO mice provided little evidence for the involvement of TRPV1 or CGRP, nor did blocking substance P receptors affect responses. However, the cholinergic antagonist atropine sulphate (5 mg/kg) significantly inhibited the depressor response and slowed HR with CA (80 micromol/kg), but had no effect on pressor responses. The pressor response remained unaffected, even in the presence of the ganglion blocker hexamethonium bromide (1 mg/kg). The alpha-adrenergic blocker prazosin hydrochloride (1 mg/kg) significantly inhibited both components, but not slowed HR.


CONCLUSIONS
TRPA1 is involved in mediating vasodilation. TRPA1 can also influence changes in blood pressure of possible relevance to autonomic system reflexes and potentially to vasovagal/neurocardiogenic syncope disorders.
Pozsgai
Gabor
G
King's College London British Heart Foundation Centre, Cardiovascular Division and Centre of Integrative Biomedicine, King's College London, Franklin-Wilkins Building, London SE1 9NH, UK.
Bodkin
Jennifer V
JV
Graepel
Rabea
R
Bevan
Stuart
S
Andersson
David A
DA
Brain
Susan D
SD
D000171:Acrolein / Q000031:analogs & derivatives / Q000494:pharmacology; D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005730:Ganglionic Blockers / Q000494:pharmacology; D006339:Heart Rate; D006439:Hemodynamics / Q000187:drug effects; D018738:Hexamethonium / Q000494:pharmacology; D017879:Isothiocyanates / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008833:Microcirculation / Q000187:drug effects; D018727:Muscarinic Antagonists / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D012039:Regional Blood Flow; D012867:Skin / Q000098:blood supply*; D013373:Substance P / Q000378:metabolism; D000074025:TRPA1 Cation Channel; D013997:Time Factors; D050051:Transient Receptor Potential Channels / Q000819:agonists / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014664:Vasodilation
D058668:Adrenergic alpha-1 Receptor Antagonists; D005730:Ganglionic Blockers; D017879:Isothiocyanates; D018727:Muscarinic Antagonists; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D013373:Substance P; D018738:Hexamethonium; D000171:Acrolein; D001285:Atropine; C004471:allyl isothiocyanate; D015740:Calcitonin Gene-Related Peptide; C012843:cinnamaldehyde; D011224:Prazosin