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This study used pharmacological gain-of-function and genetic loss-of-function approaches to test the hypothesis that the eNOS/NO/cGMP axis is central to exercise training adaptations in microcirculatory function and exercise capacity. Chronic but not acute treatment with the PDE5 inhibitor, sildenafil, synergizes with exercise training to improve performance with incremental exercise in obese mice; whereas endothelium-specific knockdown in eNOS does not blunt the microcirculatory adaptations and improvements in exercise tolerance with training.
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Winn et al. (2025) studied this question.
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