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Investigating the potential role of TRPA 1 in locomotion and cardiovascular control during hypertension
Author(s) -
Bodkin Jennifer V.,
Thakore Pratish,
Aubdool Aisah A.,
Liang Lihuan,
Fernandes Elizabeth S.,
Nandi Manasi,
Spina Domenico,
Clark James E.,
Aaronson Philip I.,
Shattock Michael J.,
Brain Susan D.
Publication year - 2014
Publication title -
pharmacology research and perspectives
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.975
H-Index - 27
ISSN - 2052-1707
DOI - 10.1002/prp2.52
Subject(s) - endocrinology , medicine , transient receptor potential channel , mesenteric arteries , blood pressure , angiotensin ii , chemistry , vasoconstriction , receptor , artery
Radiotelemetry was used to investigate the in vivo cardiovascular and activity phenotype of both TRPA 1 (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). TRPA 1 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). TRPA 1 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 ). TRPA 1 expression in dorsal root ganglion ( DRG ) neurones was upregulated during hypertension (163% of baseline expression). Investigations utilizing the TRPA 1 agonist cinnamaldehyde ( CA ) on mesenteric arterioles isolated from näive mice suggested a lack of TRPA 1‐dependent vasoreactivity in this vascular bed; a site with notable ability to alter total peripheral resistance. However, mesenteric arterioles isolated from TRPA 1 KO hypertensive mice displayed significantly reduced ability to relax in response to nitric oxide ( NO ) ( P  < 0.05). Unexpectedly, naïve TRPA 1 KO mice also displayed physical hyperactivity traits at baseline, which was exacerbated during hypertension. In conclusion, our study provides a novel cardiovascular characterization of TRPA 1 KO mice in a model of hypertension. Results suggest that TRPA 1 has a limited role in global cardiovascular control, but we demonstrate an unexpected capacity for TRPA 1 to regulate physical activity.

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