Maternal exercise improves vascular function in hypertensive offspring via A-kinase anchoring protein 150 gene...

Regular physical activity is an effective non-pharmacological approach to hypertension management and maternal exercise improves offspring cardiovascular health, although mechanisms remain unclear. A-kinase anchoring protein 150 (AKAP150) targets protein kinase Cα to L-type Ca²⁺ channels (Ca_V1.2), enhancing vascular tone in arterial smooth muscle during hypertension. This study aims to uncover a novel mechanism in which epigenetic modifications of the AKAP150 gene (Akap5) mediate the beneficial effects of maternal exercise on vascular function in hypertensive offspring.

Pregnant spontaneously hypertensive rats (SHRs) and smooth muscle-specific AKAP150 knock-in mice (AKAP150 smKI) were assigned to sedentary or exercise groups. Mesenteric arteries (MAs) from embryonic day 21 and 3-month-old offspring were analysed for vascular function, electrophysiology, gene expression and Akap5 promoter histone acetylation.

Maternal exercise during pregnancy significantly reduced blood pressure and Ca_v1.2 channel function in adult male offspring of both SHR and AKAP150 smKI, but not in female SHR offspring. Maternal exercise significantly attenuated AKAP150-Ca_v1.2 association in mesenteric arterial myocyte from SHR offspring. Additionally, it decreased H3K9ac at the Akap5 gene promoter, with a concomitant decrease in AKAP150 protein and mRNA expressions in hypertensive offspring. Furthermore, maternal exercise activated AMPK that up-regulated silent information regulator 1 (sirtuin 1; SIRT1) in the mesenteric arteries of SHR offspring.

Maternal exercise improves blood pressure and vascular function in adult male hypertensive offspring by deacetylating H3K9ac at the Akap5 promoter via AMPK/SIRT1 activation. This highlights prenatal exercise as a potential strategy to mitigate the intergenerational transmission of hypertension.