Voluntary wheel running restores endothelial function in conduit arteries of old mice: direct evidence for reduced oxidative stress, increased superoxide dismutase …

JR Durrant, DR Seals, ML Connell… - The Journal of …, 2009 - Wiley Online Library
JR Durrant, DR Seals, ML Connell, MJ Russell, BR Lawson, BJ Folian, AJ Donato
The Journal of physiology, 2009Wiley Online Library
Habitual aerobic exercise is associated with enhanced endothelium‐dependent dilatation
(EDD) in older humans, possibly by increasing nitric oxide bioavailability and reducing
oxidative stress. However, the mechanisms involved are incompletely understood. EDD was
measured in young (6–8 months) and old (29–32 months) cage control and voluntary wheel
running (VR) B6D2F1 mice. Age‐related reductions in maximal carotid artery EDD to
acetylcholine (74 vs. 96%, P< 0.01) and the nitric oxide (NO) component of EDD (maximum …
Habitual aerobic exercise is associated with enhanced endothelium‐dependent dilatation (EDD) in older humans, possibly by increasing nitric oxide bioavailability and reducing oxidative stress. However, the mechanisms involved are incompletely understood. EDD was measured in young (6–8 months) and old (29–32 months) cage control and voluntary wheel running (VR) B6D2F1 mice. Age‐related reductions in maximal carotid artery EDD to acetylcholine (74 vs. 96%, P < 0.01) and the nitric oxide (NO) component of EDD (maximum dilatation with ACh and l‐NAME minus that with ACh alone was −28%vs.−55%, P < 0.01) were restored in old VR (EDD: 96%, NO: −46%). Nitrotyrosine, a marker of oxidative stress, was increased in aorta with age, but was markedly lower in old VR (P < 0.05). Aortic superoxide dismutase (SOD) activity was greater (P < 0.01), whereas NADPH oxidase protein expression (P < 0.01) and activity (P= 0.05) were lower in old VR vs. old cage control. Increasing SOD (with 4‐hydroxy‐2,2,6,6‐tetramethylpiperidine 1‐oxyl) and inhibition of NADPH oxidase (with apocynin) improved EDD and its NO component in old cage control, but not old VR mice. VR increased endothelial NO synthase (eNOS) protein expression (P < 0.05) and activation (Ser1177 phosphorylation) (P < 0.05) in old mice. VR did not affect EDD in young mice. Our results show that voluntary aerobic exercise restores the age‐associated loss of EDD by suppression of oxidative stress via stimulation of SOD antioxidant activity and inhibition of NADPH oxidase superoxide production. Increased eNOS protein and activation also may contribute to exercise‐mediated preservation of NO bioavailability and EDD with ageing.
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