The angiotensin II signaling system regulates vascular dysfunction and is involved in the programming of hypertension. Maternal exercise has been linked to both short-term and long-term benefits for the mother and fetus. However, the impacts of maternal exercise on the intravascular renin-angiotensin system (RAS) in hypertensive offspring remain unexamined. This study examined whether maternal exercise has an epigenetic effect in repressing angiotensin II type 1 receptor (AT1R) expression, which leads to favorable alterations in the mesenteric artery (MA) function of spontaneously hypertensive offspring. Spontaneously hypertensive rats (SHRs) and Wistar–Kyoto (WKY) pregnant rats were randomly divided into an exercise group and a control group. Blood pressure, vascular tone, AT1R protein and mRNA expression, and AT1R gene (Agtr1a) promoter methylation status were examined in the MAs of 3-month-old male offspring. Maternal exercise significantly reduced the resting blood pressure and cardiovascular reactivity of offspring from SHRs. Furthermore, Ang II–AT1R activity in regulating vascular tone and AT1R expression was decreased in the MAs of the SHR offspring from the exercise groups. Importantly, exercise during gestation suppressed AT1R expression via hypermethylation of the Agtr1a promoter region and upregulated DNA methyltransferase (DNMT) expression in MAs of SHR offspring. These results suggest that maternal exercise upregulates DNMT expression, resulting in hypermethylation and repression of the Agtr1a gene, which may prevent MA dysfunction in the offspring of SHRs.
https://doi.org/10.1038/s41440-022-01124-7