Original Article | Published:

Basic Science

BKCa channel activity and vascular contractility alterations with hypertension and aging via β1 subunit promoter methylation in mesenteric arteries

Hypertension Research volume 41, pages 96103 (2018) | Download Citation

Abstract

Promoter methylation is a key mechanism in the epigenetic reprogramming of gene expression patterns. Here, we investigated the contribution of DNA methylation and the associated expression and function of large-conductance Ca2+-activated K+ (BKCa) channel in mesenteric arteries when hypertension was superimposed on aging. Male Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) at young (12 weeks), adult (36 weeks) and old (64 weeks) life stages were used. BKCa channel currents, BKCa channel activity in regulating vascular tone, and BKCa channel β1 subunit (BKβ1) function and expression were greater in mesenteric arteries from SHR than from age-matched WKY controls. Consistently, hypertension decreased CpG methylation of the BKβ1 promoter at all ages. Furthermore, aging triggered an increase in BKβ1 promoter methylation in both old WKY and SHR, with concomitant suppression of the β1 subunit and BKCa channel activity. Aging enhanced β1 gene promoter methylation and subunit expression without changing BKCa channel function between young and adult WKY animals. In contrast, aging did not alter CpG methylation but facilitated BKCa channel currents and upregulated BKβ1 expression and function in adult SHR. Taken together, our results provide compelling evidence that hypertension and aging exert opposing effects on DNA methylation at BKβ1 promoter, subsequently resulting in different β1 expression levels and functional modulation of mesenteric arterial contractility. Such information is useful in revealing the epigenetic regulation of BKCa channel function in vascular smooth muscle and in comprehensively understanding the molecular mechanisms in vascular physiology and pathophysiology.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (31771312, 31371201), the Beijing Natural Science Foundation (5172023), and the Chinese Universities Scientific Fund (2017ZD004, 2017XS021).

Author information

Author notes

    • Yanyan Zhang
    •  & Jingwen Liao

    These authors contributed equally to this work.

Affiliations

  1. Department of Exercise Physiology, Beijing Sport University, Beijing, China

    • Yanyan Zhang
    • , Lin Zhang
    • , Shanshan Li
    • , Ying Wu
    •  & Lijun Shi
  2. Guangdong Provincial Key Laboratory of Sports and Health Promotion, Department of Sport and Health Sciences, Scientific Research Center, Guangzhou Sport University, Guangzhou, China

    • Jingwen Liao

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The authors declare no conflict of interest.

Corresponding author

Correspondence to Lijun Shi.

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DOI

https://doi.org/10.1038/hr.2017.96

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