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Advanced glycation end products impair KCa3.1- and KCa2.3-mediated vasodilatation via oxidative stress in rat mesenteric arteries

  • Ion channels, receptors and transporters
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Abstract

The present study was designed to investigate the role of advanced glycation end products (AGEs) in intermediate-conductance and small-conductance Ca2+-activated potassium channels (KCa3.1 and KCa2.3)-mediated relaxation in rat resistance arteries and the underlying mechanism. The endothelial function of mesenteric arteries was assessed with the use of wire myography. Expression levels of KCa3.1 and KCa2.3 were measured by using Western blot. Reactive oxygen species (ROS) were measured by using dihydroethidium and 2′, 7′-dichlorofluorescein diacetate. KCa3.1 and KCa2.3-mediated vasodilatation responses to acetylcholine and NS309 (opener of KCa3.1 and KCa2.3) were impaired by incubation of the third-order mesenteric arteries from normal rats with AGEs (200 μg ml−1 for 3 h). In cultured human umbilical vein endothelial cells (HUVECs), AGEs increased ROS level and decreased the protein expression of KCa3.1 and KCa2.3. Antioxidant alpha lipoic acid restored the impairment in both vasodilatation function and expression of KCa3.1 and KCa2.3. H2O2 could mimic the effect of AGEs on the protein expression of KCa3.1 and KCa2.3 in cultured HUVECs. These results demonstrate for the first time that AGEs impaired KCa3.1 and KCa2.3-mediated vasodilatation in rat mesenteric arteries via downregulation of both KCa3.1 and KCa2.3, in which the enhanced oxidative stress was involved.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (grant number 81100231, 81170137 and 81200097) and the Natural Science Foundation of Shaanxi Province (grant number 2011JQ4021). The authors are grateful for substantial support from Professor Lang-Chong He, School of Medicine, Xi’an Jiaotong University.

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The authors have no conflicts of interest to disclose.

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Authors and Affiliations

  1. Department of Physiology and Pathophysiology, School of Medicine, Xi’an Jiaotong University, 76 West Yanta Road, Xi’an, 710061, Shaanxi, China

    Li-Mei Zhao, Yan Wang, Xiao-Zhen Ma, Nan-Ping Wang & Xiu-Ling Deng

  2. Cardiovascular Research Center, School of Medicine, Xi’an Jiaotong University, 76 West Yanta Road, Xi’an, 710061, Shaanxi, China

    Li-Mei Zhao, Yan Wang, Nan-Ping Wang & Xiu-Ling Deng

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  1. Li-Mei Zhao
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Correspondence to Xiu-Ling Deng.

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Zhao, LM., Wang, Y., Ma, XZ. et al. Advanced glycation end products impair KCa3.1- and KCa2.3-mediated vasodilatation via oxidative stress in rat mesenteric arteries. Pflugers Arch - Eur J Physiol 466, 307–317 (2014). https://doi.org/10.1007/s00424-013-1324-y

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  • DOI: https://doi.org/10.1007/s00424-013-1324-y

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