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Aerobic training-mediated DNA hypermethylation of Agtr1a and Mas1 genes ameliorate mesenteric arterial function in spontaneously hypertensive rats

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Abstract

Background

The imbalance of vasoconstrictor and vasodilator axes of the renin-angiotensin system (RAS) is observed in hypertension. Exercise regulates RAS level and improves vascular function. This study focused on the contribution of RAS axes in vascular function of mesenteric arteries and exercise-induced DNA methylation of the Agtr1a (AT1aR) and Mas1 (MasR) genes in hypertension.

Methods

Spontaneously hypertensive rats (SHRs) and Wistar-Kyoto rats were randomized into exercise or sedentary group. Levels of plasma RAS components, vascular tone, and DNA methylation markers were measured.

Results

Blood pressure of SHR was markedly reduced after 12 weeks of aerobic exercise. RAS peptides in plasma were all increased with an imbalanced upregulation of Ang II and Ang-(1–7) in SHR, exercise revised the level of RAS and increased Ang-(1–7)/Ang II. The vasoconstriction response induced by Ang II was mainly via type 1 receptors (AT1R), while this contraction was inhibited by Mas receptor (MasR). mRNA and protein of AT1R and MasR were both upregulated in SHR, whereas exercise significantly suppressed this imbalanced increase and increased MasR/AT1R ratio. Exercise hypermethylated Agtr1a and Mas1 genes, associating with increased DNMT1 and DNMT3b and SAM/SAH.

Conclusions

Aerobic exercise ameliorates vascular function via hypermethylation of the Agtr1a and Mas1 genes and restores the vasoconstrictor and vasodilator axes balance.

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Acknowledgements

We are greatly thankful for the support of Metabolomics Facility at Technology Center for Protein Sciences in Tsinghua University.

Funding

This work was supported by the National Natural Science Foundation of China [Grant numbers 32071174 and 31771312 (L.S.)]; and the Chinese Universities Scientific Fund [Grant number 2020049 (L.S.)].

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Author notes

  1. Yu Chen and Shanshan Li have contributed equally to this work.

Authors and Affiliations

  1. Department of Exercise Physiology, Beijing Sport University, Beijing, 100084, China

    Yu Chen, Shanshan Li, Zhaoxia Xu, Yanyan Zhang, Huirong Zhang & Lijun Shi

  2. Key Laboratory of Physical Fitness and Exercise, Ministry of Education, Beijing Sport University, Beijing, 100084, China

    Lijun Shi

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  1. Yu Chen
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  3. Zhaoxia Xu
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Contributions

Conceptualization, Y.C. and L.J.S; investigation, Y.C, S.S.L, Y.Y.Z, H.R.Z; methodology, Z.X.X; writing-review and editing, Y.C and L.J.S; funding acquisition, L.J.S.

Corresponding author

Correspondence to Lijun Shi.

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The authors declare that they have no conflict of interest.

Ethical approval

All experiments were approved by the ethical committee of Beijing Sport University and were performed in accordance with the Chinese animal protection laws and institutional guidelines.

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Chen, Y., Li, S., Xu, Z. et al. Aerobic training-mediated DNA hypermethylation of Agtr1a and Mas1 genes ameliorate mesenteric arterial function in spontaneously hypertensive rats. Mol Biol Rep 48, 8033–8044 (2021). https://doi.org/10.1007/s11033-021-06929-2

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