TRPM8 downregulation by angiotensin II in vascular smooth muscle cells is involved in hypertension

  • Authors:
    • Fang Huang
    • Min Ni
    • Jing‑Ming Zhang
    • Dong‑Jie Li
    • Fu‑Ming Shen
  • View Affiliations

  • Published online on: January 30, 2017     https://doi.org/10.3892/mmr.2017.6158
  • Pages: 1900-1908
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Abstract

Angiotensin II (Ang II)-induced injury of vascular smooth muscle cells (VSMCs) serves an important role in hypertension and other cardiovascular disorders. Transient receptor potential melastatin 8 (TRPM8) is a thermally‑regulated Ca2+‑permeable channel that is activated by reduced body temperature. Although several recent studies have revealed the regulatory effect of TRPM8 in vascular tone and hypertension, the precise role of TRPM8 in dysfunction of vascular smooth muscle cells (VSMCs) induced by Ang II remains elusive. In the present study, the possible function of TRPM8 in Ang II‑induced VSMCs malfunction in vivo and in vitro was investigated. In the aortae from rats that had undergone a two‑kidney one‑clip operation, which is a widely‑used renovascular hypertension model, the mRNA and protein levels of TRPM8 were reduced. In addition, exogenous Ang II treatment decreased TRPM8 mRNA and protein expression levels in primary cultures of rat VSMCs. TRPM8 activation by menthol, a pharmacological agonist, in VSMCs, significantly attenuated the Ang II‑induced increase in reactive oxygen species and H2O2 production. In addition, TRPM8 activation reduced the Ang II‑induced upregulation of NADPH oxidase (NOX) 1 and NOX4 in VSMCs. Furthermore, TRPM8 activation relieved the Ang II‑induced activation of ras homolog gene family, member A‑rho associated protein kinase 2 and janus kinase 2 signaling pathways in VSMCs. In conclusion, the results presented in the current study indicated that TRPM8 downregulation by Ang II in VSMCs may be involved in hypertension.
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April-2017
Volume 15 Issue 4

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Huang F, Ni M, Zhang JM, Li DJ and Shen FM: TRPM8 downregulation by angiotensin II in vascular smooth muscle cells is involved in hypertension. Mol Med Rep 15: 1900-1908, 2017
APA
Huang, F., Ni, M., Zhang, J., Li, D., & Shen, F. (2017). TRPM8 downregulation by angiotensin II in vascular smooth muscle cells is involved in hypertension. Molecular Medicine Reports, 15, 1900-1908. https://doi.org/10.3892/mmr.2017.6158
MLA
Huang, F., Ni, M., Zhang, J., Li, D., Shen, F."TRPM8 downregulation by angiotensin II in vascular smooth muscle cells is involved in hypertension". Molecular Medicine Reports 15.4 (2017): 1900-1908.
Chicago
Huang, F., Ni, M., Zhang, J., Li, D., Shen, F."TRPM8 downregulation by angiotensin II in vascular smooth muscle cells is involved in hypertension". Molecular Medicine Reports 15, no. 4 (2017): 1900-1908. https://doi.org/10.3892/mmr.2017.6158