title: Investigating the potential role of TRPA1 in locomotion and cardiovascular control during hypertension.
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.affiliation: Cardiovascular Division, BHF Centre of Excellence and Centre of Integrative Biomedicine, School of Medicine, King's College London London, SE1 9NH, U.K.
authors.forename: Jennifer V
authors.initials: JV
authors.lastname: Bodkin
authors.affiliation: Cardiovascular Division, BHF Centre of Excellence and Centre of Integrative Biomedicine, School of Medicine, King's College London London, SE1 9NH, U.K ; Pharmaceutical Sciences Division, School of Biomedical Sciences, King's College London London, SE1 9NH, U.K.
authors.forename: Pratish
authors.initials: P
authors.lastname: Thakore
authors.affiliation: Cardiovascular Division, BHF Centre of Excellence and Centre of Integrative Biomedicine, School of Medicine, King's College London London, SE1 9NH, U.K.
authors.forename: Aisah A
authors.initials: AA
authors.lastname: Aubdool
authors.affiliation: Cardiovascular Division, BHF Centre of Excellence and Centre of Integrative Biomedicine, School of Medicine, King's College London London, SE1 9NH, U.K.
authors.forename: Lihuan
authors.initials: L
authors.lastname: Liang
authors.affiliation: Cardiovascular Division, BHF Centre of Excellence and Centre of Integrative Biomedicine, School of Medicine, King's College London London, SE1 9NH, U.K ; Programa de Pós-Graduação em Biologia Parasitária, Universidade Ceuma São Luís, Brazil.
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Fernandes
authors.affiliation: Pharmaceutical Sciences Division, School of Biomedical Sciences, King's College London London, SE1 9NH, U.K.
authors.forename: Manasi
authors.initials: M
authors.lastname: Nandi
authors.affiliation: Pharmaceutical Sciences Division, School of Biomedical Sciences, King's College London London, SE1 9NH, U.K.
authors.forename: Domenico
authors.initials: D
authors.lastname: Spina
authors.affiliation: Cardiovascular Division, BHF Centre of Excellence and Centre of Integrative Biomedicine, School of Medicine, King's College London London, SE1 9NH, U.K.
authors.forename: James E
authors.initials: JE
authors.lastname: Clark
authors.affiliation: Asthma, Allergy and Lung Biology Division, School of Medicine, King's College London London, SE1 1UL, U.K.
authors.forename: Philip I
authors.initials: PI
authors.lastname: Aaronson
authors.affiliation: Cardiovascular Division, BHF Centre of Excellence and Centre of Integrative Biomedicine, School of Medicine, King's College London London, SE1 9NH, U.K.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Shattock
authors.affiliation: Cardiovascular Division, BHF Centre of Excellence and Centre of Integrative Biomedicine, School of Medicine, King's College London London, SE1 9NH, U.K.
authors.forename: Susan D
authors.initials: SD
authors.lastname: Brain
keywords: Blood pressure; TRPA1; cinnamaldehyde; hypertension; locomotion