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    Investigating the potential role of TRPA1 in locomotion and cardiovascular control during hypertension. 
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    • Investigating the potential role of TRPA1 in locomotion and cardiovascular control during hypertension.
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    Investigating the potential role of TRPA1 in locomotion and cardiovascular control during hypertension.

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    Published version (2.131Mb)
    Volume
    2
    Pagination
    e00052 - ?
    DOI
    10.1002/prp2.52
    Journal
    Pharmacol Res Perspect
    Issue
    4
    ISSN
    2052-1707
    Metadata
    Show full item record
    Abstract
    Radiotelemetry was used to investigate the in vivo cardiovascular and activity phenotype of both TRPA1 (transient receptor potential ankyrin 1) wild-type (WT) and TRPA1 knockout (KO) mice. After baseline recording, experimental hypertension was induced using angiotensin II infusion (1.1 mg(-1) kg(-1) a day, for 14 days). TRPA1 WT and KO mice showed similar morphological and functional cardiovascular parameters, including similar basal blood pressure (BP), heart rate, size, and function. Similar hypertension was also displayed in response to angiotensin II (156 ± 7 and 165 ± 11 mmHg, systolic BP ± SEM, n = 5-6). TRPA1 KO mice showed increased hypertensive hypertrophy (heart weight:tibia length: 7.3 ± 1.6 mg mm(-1) vs. 8.8 ± 1.7 mg mm(-1)) and presented with blunted interleukin 6 (IL-6) production compared with hypertensive WT mice (151 ± 24 vs. 89 ± 16 pg mL(-1)). TRPA1 expression in dorsal root ganglion (DRG) neurones was upregulated during hypertension (163% of baseline expression). Investigations utilizing the TRPA1 agonist cinnamaldehyde (CA) on mesenteric arterioles isolated from näive mice suggested a lack of TRPA1-dependent vasoreactivity in this vascular bed; a site with notable ability to alter total peripheral resistance. However, mesenteric arterioles isolated from TRPA1 KO hypertensive mice displayed significantly reduced ability to relax in response to nitric oxide (NO) (P < 0.05). Unexpectedly, naïve TRPA1 KO mice also displayed physical hyperactivity traits at baseline, which was exacerbated during hypertension. In conclusion, our study provides a novel cardiovascular characterization of TRPA1 KO mice in a model of hypertension. Results suggest that TRPA1 has a limited role in global cardiovascular control, but we demonstrate an unexpected capacity for TRPA1 to regulate physical activity.
    Authors
    Bodkin, JV; Thakore, P; Aubdool, AA; Liang, L; Fernandes, ES; Nandi, M; Spina, D; Clark, JE; Aaronson, PI; Shattock, MJ
    URI
    http://qmro.qmul.ac.uk/xmlui/handle/123456789/15222
    Collections
    • Centre for Cell Biology and Cutaneous Research [327]
    Language
    eng
    Licence information
    CC-BY
    Copyright statements
    © 2014 The Authors.
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