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Pharmacol Res Perspect. 2014 Aug;2(4):e00052. doi: 10.1002/prp2.52. Epub 2014 Jun 23.

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

Pharmacology research & perspectives

Jennifer V Bodkin, Pratish Thakore, Aisah A Aubdool, Lihuan Liang, Elizabeth S Fernandes, Manasi Nandi, Domenico Spina, James E Clark, Philip I Aaronson, Michael J Shattock, Susan D Brain

Affiliations

  1. Cardiovascular Division, BHF Centre of Excellence and Centre of Integrative Biomedicine, School of Medicine, King's College London London, SE1 9NH, U.K.
  2. 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.
  3. 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.
  4. Pharmaceutical Sciences Division, School of Biomedical Sciences, King's College London London, SE1 9NH, U.K.
  5. Asthma, Allergy and Lung Biology Division, School of Medicine, King's College London London, SE1 1UL, U.K.

PMID: 25505598 PMCID: PMC4186440 DOI: 10.1002/prp2.52

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.

Keywords: Blood pressure; TRPA1; cinnamaldehyde; hypertension; locomotion

References

  1. Cardiovasc Res. 2010 Sep 1;87(4):760-8 - PubMed
  2. Pain. 2009 Apr;142(3):264-74 - PubMed
  3. J Exp Biol. 2011 Jan 15;214(Pt 2):206-29 - PubMed
  4. J Neurosci. 2013 Jun 12;33(24):10143-53 - PubMed
  5. Pain. 2011 Jan;152(1):38-44 - PubMed
  6. Anat Cell Biol. 2013 Mar;46(1):68-78 - PubMed
  7. Am J Physiol Heart Circ Physiol. 2006 Mar;290(3):H935-40 - PubMed
  8. Eur J Heart Fail. 2011 Oct;13(10):1087-95 - PubMed
  9. J Pharmacobiodyn. 1982 Aug;5(8):539-46 - PubMed
  10. Genome Biol. 2002 Jun 18;3(7):RESEARCH0034 - PubMed
  11. Circulation. 2003 Feb 25;107(7):984-91 - PubMed
  12. Vasc Health Risk Manag. 2011;7:273-80 - PubMed
  13. Behav Genet. 1998 May;28(3):227-37 - PubMed
  14. Cardiovasc Diabetol. 2010 Oct 11;9:62 - PubMed
  15. Hypertension. 2014 May;63(5):1056-62 - PubMed
  16. Circulation. 1995 Apr 1;91(7):1981-7 - PubMed
  17. J Invest Dermatol. 2009 Sep;129(9):2312-5 - PubMed
  18. Eur J Pharmacol. 2012 Aug 15;689(1-3):56-64 - PubMed
  19. Arthritis Rheum. 2011 Mar;63(3):819-29 - PubMed
  20. Hypertens Res. 2011 Jan;34(1):5-14 - PubMed
  21. Br J Pharmacol. 2012 Sep;167(1):13-22 - PubMed
  22. Neuroreport. 2005 Jun 21;16(9):955-9 - PubMed
  23. Neuron. 2004 Mar 25;41(6):849-57 - PubMed
  24. Naunyn Schmiedebergs Arch Pharmacol. 2012 Jun;385(6):555-63 - PubMed
  25. Peptides. 2010 Apr;31(4):736-56 - PubMed
  26. Brain Res Rev. 2008 Jan;57(1):183-91 - PubMed
  27. Braz J Med Biol Res. 2011 Sep;44(9):920-32 - PubMed
  28. Biochem Biophys Res Commun. 2007 Jul 13;358(4):1058-64 - PubMed
  29. Curr Opin Nephrol Hypertens. 2006 Mar;15(2):152-8 - PubMed
  30. Circulation. 2000 Apr 25;101(16):1899-906 - PubMed
  31. Arch Oral Biol. 2000 Jan;45(1):53-61 - PubMed
  32. Hypertension. 2013 Jan;61(1):246-52 - PubMed
  33. Biochem Pharmacol. 2013 Feb 1;85(3):426-38 - PubMed
  34. Neuroscience. 1989;32(3):581-6 - PubMed
  35. Acta Physiol (Oxf). 2011 Sep;203(1):87-98 - PubMed
  36. J Appl Physiol (1985). 1999 Nov;87(5):1877-86 - PubMed
  37. Chem Pharm Bull (Tokyo). 1975 May;23(5):941-7 - PubMed
  38. J Neurosci. 2008 Mar 5;28(10):2485-94 - PubMed
  39. Hypertension. 1983 Nov-Dec;5(6):881-6 - PubMed
  40. Physiol Rev. 2008 Oct;88(4):1379-406 - PubMed
  41. Biol Pharm Bull. 2006 Dec;29(12):2415-8 - PubMed
  42. Biosci Biotechnol Biochem. 2008 Oct;72(10):2608-14 - PubMed
  43. G3 (Bethesda). 2013 Oct 03;3(10):1629-37 - PubMed
  44. J Biol Chem. 2012 Sep 14;287(38):31962-72 - PubMed
  45. J Biol Chem. 1999 Mar 12;274(11):7325-33 - PubMed
  46. Environ Health Perspect. 2011 Jul;119(7):951-7 - PubMed
  47. Bioorg Med Chem Lett. 2011 Aug 15;21(16):4857-9 - PubMed
  48. Integr Comp Biol. 2005 Jun;45(3):438-55 - PubMed
  49. Eur J Pharmacol. 2005 Jan 10;507(1-3):273-80 - PubMed
  50. J Pharmacol Exp Ther. 2011 Apr;337(1):117-24 - PubMed
  51. J Am Acad Dermatol. 2001 Jul;45(1):62-7 - PubMed
  52. Proc Natl Acad Sci U S A. 2007 Aug 14;104(33):13519-24 - PubMed
  53. Hypertension. 2010 Aug;56(2):225-31 - PubMed
  54. Circ Res. 2009 Apr 24;104(8):987-94 - PubMed
  55. Cell. 2003 Mar 21;112(6):819-29 - PubMed
  56. J Vis Exp. 2010 May 28;(39):null - PubMed

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