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Aerobic exercise improves BKCa channel-mediated vasodilation in diabetic vascular smooth muscle via AMPK/Nrf2/HO-1 pathway

Aims This study aims to investigate the effect of aerobic exercise training on BK Ca channel in diabetic vascular smooth muscle and explore the underlying mechanism. Methods Control m/m mice and diabetic db/db mice were randomly assigned to sedentary groups (W and D) and exercise training groups (WE...

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Published in:Acta diabetologica 2024-04, Vol.61 (4), p.425-434
Main Authors: Liu, Yujia, Cheng, Yue, Xiang, Na, Wang, Zhiyuan, Li, Siyu, Gong, Lijing, Wang, Xingqi
Format: Article
Language:English
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Summary:Aims This study aims to investigate the effect of aerobic exercise training on BK Ca channel in diabetic vascular smooth muscle and explore the underlying mechanism. Methods Control m/m mice and diabetic db/db mice were randomly assigned to sedentary groups (W and D) and exercise training groups (WE and DE). Mice in exercise groups underwent training sessions lasting for 12 weeks, with a speed of 12 m/min for 60 min, five times per week. The thoracic aorta was extracted isolated and examined for measurement of vascular structure, global levels of reactive oxygen species (ROS), vasodilation, and protein expression. Rat thoracic aorta vascular smooth muscle cells (USMCs) were cultured, and siRNA transfection was conducted to detect whether AMPK contributed to the regulation. ROS level and protein expression were measured. Results Compared with control mice, diabetic mice had a larger vascular medium thickness, impaired BK Ca -mediated vasodilation, a higher level of ROS, and a lower expression of BK Ca α, BK Ca β1, Nrf2, p -Nrf2, p -Nrf2/Nrf2, HO-1, and p -AMPK/AMPK. Exercise training increased the expression of BK Ca α, Nrf2, p -Nrf2, p -Nrf2/Nrf2, HO-1, and p -AMPK/AMPK. AMPK deletion led to lower ROS levels and expression of BK Ca α, β1, Nrf2, and HO-1 in USMCs cultured in high glucose conditions. Conclusions BK Ca channel protein expression reduction in VSMCs contributes to vasodilation and vascular remodeling dysfunction in diabetes mellitus. Aerobic exercise can promote the expression of BK Ca channel and improve BK Ca -mediated vascular dysfunction in diabetic VSMCs through AMPK/Nrf2/HO-1 signaling pathway.
ISSN:1432-5233
0940-5429
1432-5233
DOI:10.1007/s00592-023-02210-z