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Keywords:

  • aging;
  • endothelial function;
  • nicotinamide adenine dinucleotide phosphate oxidase;
  • nitrotyrosine;
  • nuclear factor kappa B;
  • superoxide dismutase

Summary

We tested the hypothesis that older men who perform habitual aerobic exercise do not demonstrate age-associated vascular endothelial oxidative stress compared with their sedentary peers. Older exercising men (n = 13, 62 ± 2 years) had higher (< 0.05) physical activity (79 ± 7 vs. 30 ± 6 MET hours per week) and maximal exercise oxygen consumption (42 ± 1 vs. 29 ± 1 mL kg−1 per minute) vs. sedentary men (n = 28, 63 ± 1 years). Brachial artery flow-mediated dilation (FMD), a measure of vascular endothelial function, was greater (< 0.05) in the exercising vs. sedentary older men (6.3 ± 0.5 vs. 4.9 ± 0.4%Δ) and not different than young controls (n = 20, 25 ± 1 years, 7.1 ± 0.5%Δ). In vascular endothelial cells sampled from the brachial artery, nitrotyrosine, a marker of oxidative stress, was 51% lower in the exercising vs. sedentary older men (0.38 ± 0.06 vs. 0.77 ± 0.10 AU). This was associated with lower endothelial expression of the oxidant enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (p47phox subunit, 0.33 ± 0.05 vs. 0.61 ± 0.09 AU) and the redox-sensitive transcription factor nuclear factor kappa B (NFκB) (p65 subunit, 0.36 ± 0.05 vs. 0.72 ± 0.09 AU). Expression of the antioxidant enzyme manganese superoxide dismutase (SOD) (0.57 ± 0.13 vs. 0.30 ± 0.04 AU) and activity of endothelium-bound extracellular SOD were greater (6.4 ± 0.5 vs. 5.0 ± 0.6 U mL−1 per minute) in the exercising men (both < 0.05), but differences no longer were significant after correcting for adiposity and circulating metabolic factors. Overall, values for the young controls differed with those for the sedentary, but not the exercising older men. Older men who exercise regularly do not demonstrate vascular endothelial oxidative stress, and this may be a key molecular mechanism underlying their reduced risk of cardiovascular diseases.