PMID- 20442136
OWN - NLM
STAT- MEDLINE
DCOM- 20101215
LR  - 20210702
IS  - 1755-3245 (Electronic)
IS  - 0008-6363 (Linking)
VI  - 87
IP  - 4
DP  - 2010 Sep 1
TI  - Evidence for the pathophysiological relevance of TRPA1 receptors in the 
      cardiovascular system in vivo.
PG  - 760-8
LID - 10.1093/cvr/cvq118 [doi]
AB  - AIMS: 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. METHODS AND 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. CONCLUSION: 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.
FAU - Pozsgai, Gabor
AU  - Pozsgai G
AD  - 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.
FAU - Bodkin, Jennifer V
AU  - Bodkin JV
FAU - Graepel, Rabea
AU  - Graepel R
FAU - Bevan, Stuart
AU  - Bevan S
FAU - Andersson, David A
AU  - Andersson DA
FAU - Brain, Susan D
AU  - Brain SD
LA  - eng
GR  - BB/E527098/1/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
GR  - G0500847/Medical Research Council/United Kingdom
GR  - PG/06/030/20579/British Heart Foundation/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100503
PL  - England
TA  - Cardiovasc Res
JT  - Cardiovascular research
JID - 0077427
RN  - 0 (Adrenergic alpha-1 Receptor Antagonists)
RN  - 0 (Ganglionic Blockers)
RN  - 0 (Isothiocyanates)
RN  - 0 (Muscarinic Antagonists)
RN  - 0 (TRPA1 Cation Channel)
RN  - 0 (Transient Receptor Potential Channels)
RN  - 0 (Trpa1 protein, mouse)
RN  - 33507-63-0 (Substance P)
RN  - 3C9PSP36Z2 (Hexamethonium)
RN  - 7864XYD3JJ (Acrolein)
RN  - 7C0697DR9I (Atropine)
RN  - BN34FX42G3 (allyl isothiocyanate)
RN  - JHB2QIZ69Z (Calcitonin Gene-Related Peptide)
RN  - SR60A3XG0F (cinnamaldehyde)
RN  - XM03YJ541D (Prazosin)
SB  - IM
MH  - Acrolein/analogs & derivatives/pharmacology
MH  - Adrenergic alpha-1 Receptor Antagonists/pharmacology
MH  - Animals
MH  - Atropine/pharmacology
MH  - Blood Pressure
MH  - Calcitonin Gene-Related Peptide/genetics/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Ganglionic Blockers/pharmacology
MH  - Heart Rate
MH  - *Hemodynamics/drug effects
MH  - Hexamethonium/pharmacology
MH  - Isothiocyanates/pharmacology
MH  - Male
MH  - Mesenteric Arteries/drug effects/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - *Microcirculation/drug effects
MH  - Muscarinic Antagonists/pharmacology
MH  - Prazosin/pharmacology
MH  - Regional Blood Flow
MH  - Skin/*blood supply
MH  - Substance P/metabolism
MH  - TRPA1 Cation Channel
MH  - Time Factors
MH  - Transient Receptor Potential Channels/agonists/deficiency/genetics/*metabolism
MH  - Vasodilation
EDAT- 2010/05/06 06:00
MHDA- 2010/12/16 06:00
CRDT- 2010/05/06 06:00
PHST- 2010/05/06 06:00 [entrez]
PHST- 2010/05/06 06:00 [pubmed]
PHST- 2010/12/16 06:00 [medline]
AID - cvq118 [pii]
AID - 10.1093/cvr/cvq118 [doi]
PST - ppublish
SO  - Cardiovasc Res. 2010 Sep 1;87(4):760-8. doi: 10.1093/cvr/cvq118. Epub 2010 May 3.