Department of Exercise Physiology, Beijing Sport University, Beijing, 100084, China.
Key Laboratory of Physical Fitness and Exercise, Ministry of Education, Beijing Sport University, Beijing, 100084, China.
Mol Biol Rep. 2021 Dec;48(12):8033-8044. doi: 10.1007/s11033-021-06929-2. Epub 2021 Nov 7.
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 (ATR) and Mas1 (MasR) genes in hypertension.
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.
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 (ATR), while this contraction was inhibited by Mas receptor (MasR). mRNA and protein of ATR and MasR were both upregulated in SHR, whereas exercise significantly suppressed this imbalanced increase and increased MasR/ATR ratio. Exercise hypermethylated Agtr1a and Mas1 genes, associating with increased DNMT1 and DNMT3b and SAM/SAH.
Aerobic exercise ameliorates vascular function via hypermethylation of the Agtr1a and Mas1 genes and restores the vasoconstrictor and vasodilator axes balance.
肾素-血管紧张素系统（RAS）的血管收缩和舒张轴失衡与高血压有关。运动调节 RAS 水平，改善血管功能。本研究主要关注 RAS 轴在高血压大鼠肠系膜动脉血管功能和运动诱导的 Agtr1a（ATR）和 Mas1（MasR）基因 DNA 甲基化中的作用。
自发性高血压大鼠（SHR）和 Wistar-Kyoto 大鼠随机分为运动组或安静组。测量血浆 RAS 成分水平、血管张力和 DNA 甲基化标志物。
12 周有氧运动后 SHR 的血压明显降低。SHR 血浆中 RAS 肽均升高，Ang II 和 Ang-（1-7）呈不平衡上调，运动修正了 RAS 水平并增加了 Ang-（1-7）/Ang II。Ang II 诱导的血管收缩反应主要通过 1 型受体（ATR），而 Mas 受体（MasR）抑制了这种收缩。ATR 和 MasR 的 mRNA 和蛋白在 SHR 中均上调，而运动显著抑制了这种不平衡的增加并增加了 MasR/ATR 比值。运动使 Agtr1a 和 Mas1 基因超甲基化，与 DNMT1 和 DNMT3b 增加以及 SAM/SAH 相关。
有氧运动通过 Agtr1a 和 Mas1 基因的超甲基化改善血管功能，并恢复血管收缩和舒张轴的平衡。
