Tao Tao
Wei Zhao
Lisha Wei
Fan She
Pei Wang
Yeqiong Li
Yanyan Zheng
Xin Chen
Wei Wang
Yanning Qiao
Xue-Na Zhang
Min-Sheng Zhu
aModel Animal Research Center and MOE Key Laboratory of Model Animal and Disease Study, Nanjing University, Nanjing, 210061, China
bKey Laboratory of MOE for Modern Teaching Technology, Shaanxi Normal University, Xi'an, 710062, China
More InformationCorresponding author: E-mail address: zhangxn@nicemice.cn (Xue-Na Zhang);E-mail address: zhums@nju.edu.cn (Min-Sheng Zhu)
Received Date: 2018-12-03
Accepted Date:2019-02-20
Rev Recd Date:2019-01-21
Available Online: 2019-03-15 Publish Date:2019-03-20
Abstract
Abstract
Several factors have been implicated in obesity-related hypertension, but the genesis of the hypertension is largely unknown. In this study, we found a significantly upregulated expression of CPI-17 (C-kinase-potentiated protein phosphatase 1 inhibitor of 17?kDa) and protein kinase C (PKC) isoforms in the vascular smooth muscles of high-fat diet (HFD)-fed obese mice. The obese wild-type mice showed a significant elevation of blood pressure and enhanced calcium-sensitized contraction of vascular smooth muscles. However, the obese CPI-17-deficient mice showed a normotensive blood pressure, and the calcium-sensitized contraction was consistently reduced. In addition, the mutant muscle displayed an abolished responsive force to a PKC activator and a 30%–50% reduction in both the initial peak force and sustained force in response to various G protein-coupled receptor (GPCR) agonists. Our observations showed that CPI-17-mediated calcium sensitization is mediated through a GPCR/PKC/CPI-17/MLCP/RLC signaling pathway. We therefore propose that the upregulation of CPI-17-mediated calcium-sensitized vasocontraction by obesity contributes to the development of obesity-related hypertension.Keywords: CPI-17,
Calcium sensitization,
Obesity-related hypertension
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