Activation of cold-sensing transient receptor potential melastatin subtype 8 antagonizes vasoconstriction and hypertension through attenuating RhoA/Rho kinase pathway

Sun, Jing, Yang, Tao, Wang, Peijan, Ma, Shuangtao, Zhu, Zhenyu, Pu, Yunfei, Li, Li, Zhao, Yu, Xiong, Shiqiang, Liu, Daoyan and Zhu, Zhiming (2014) Activation of cold-sensing transient receptor potential melastatin subtype 8 antagonizes vasoconstriction and hypertension through attenuating RhoA/Rho kinase pathway. Hypertension, 63 6: 1354-1363. doi:10.1161/HYPERTENSIONAHA.113.02573


Author Sun, Jing
Yang, Tao
Wang, Peijan
Ma, Shuangtao
Zhu, Zhenyu
Pu, Yunfei
Li, Li
Zhao, Yu
Xiong, Shiqiang
Liu, Daoyan
Zhu, Zhiming
Title Activation of cold-sensing transient receptor potential melastatin subtype 8 antagonizes vasoconstriction and hypertension through attenuating RhoA/Rho kinase pathway
Journal name Hypertension   Check publisher's open access policy
ISSN 1524-4563
0194-911X
Publication date 2014-06-01
Year available 2014
Sub-type Article (original research)
DOI 10.1161/HYPERTENSIONAHA.113.02573
Open Access Status Not Open Access
Volume 63
Issue 6
Start page 1354
End page 1363
Total pages 10
Place of publication Philadelphia PA, United States
Publisher Lippincott Williams & Wilkins
Language eng
Abstract Environmental cold is a nonmodifiable hypertension risk factor. Transient receptor potential melastatin subtype 8 (TRPM8) is a cold-sensing cation channel that can be activated by menthol, a compound with a naturally cold sensation in mint. Little is known about the effect of TRPM8 activation on vascular function and blood pressure. Here, we report that TRPM8 is abundantly expressed in the vasculature. TRPM8 activation by menthol attenuated vasoconstriction via RhoA/Rho kinase pathway inhibition in wild-type mice, but the effect was absent in TRPM8-/- mice. Chronic dietary menthol blunted mesenteric arterial constriction and lowered blood pressure in genetic hypertensive rats via inhibition of RhoA/Rho kinase expression and activity in the vivo study. TRPM8 effect was associated with inhibition of intracellular calcium release from the sarcoplasmic reticulum, RhoA/Rho kinase activity, and sustained arterial contraction in the vitro study. Importantly, 8-week chronic menthol capsule treatment moderately lowered systolic blood pressure and diastolic blood pressure in prehypertensive individuals compared with the placebo group. Furthermore, chronic menthol capsule administration also improved flowmediated dilatation in prehypertensive individuals, but not in the placebo group. In conclusion, our study demonstrates that TRPM8 activation by menthol benefits vascular function and blood pressure by inhibiting calcium signaling-mediated RhoA/Rho kinase activation in the vasculature. These findings add to the evidence that long-term dietary menthol treatment had favorable effects on hypertension treatment.
Keyword Hypertension
Menthol
Muscle
Smooth, vascular
Rho-associated kinases
TRPM8 protein, human
Vasoconstriction
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
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