Habitual aerobic exercise prevents age-related impairments in endothelium-dependent dilation (EDD). We have hypothesized that the pro-inflammatory transcription factor nuclear factor κB (NF-κB) impairs EDD with sedentary aging, and habitual aerobic exercise prevents this age-related suppression of EDD by NF-κB. To test this hypothesis, we have inhibited NF-κB signalling via oral salsalate administration in healthy older aerobic exercise-trained adults (OT, n=14, 58±2 years), older non-exercising adults (ON, n=16, 61±1 years) and young non-exercising controls (YN, n=8, 23±1 years). Salsalate reduced endothelial cell expression of NF-κB p65 by ~25% in ON (P<0.05) but did not significantly change expression in OT or YN (P>0.05). EDD, assessed by brachial artery flow-mediated dilation (FMD), was improved by salsalate in ON (4.0±0.7% compared with 6.8±0.7%, placebo compared with salsalate, P<0.001) but did not change with salsalate in OT or YN (OT: 7.2±0.7% compared with 7.7±0.6%; YN: 7.6±0.9% compared with 8.1±0.8%; placebo compared with salsalate, P>0.05). Endothelium-independent dilation was not affected by salsalate in any group (P>0.05). In ON, vitamin C infusion improved FMD by ~30% during placebo (P<0.001) but had no affect during salsalate (P>0.05). In OT and YN, vitamin C infusion did not affect FMD during either placebo or salsalate (P>0.05). Salsalate reduced endothelial cell nitrotyrosine content by ~25% and NADPH oxidase p47phox expression by ~30% in ON (P<0.05) but had no effect in OT or YN (P>0.05). Our results suggest that endothelial NF-κB signalling is associated with oxidative stress-related impairment of EDD in healthy non-exercising but not aerobically exercising older adults. This may be a key mechanism by which regular aerobic exercise preserves endothelial function and reduces cardiovascular risk with aging.
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Research Article|
July 29 2014
Prevention of age-related endothelial dysfunction by habitual aerobic exercise in healthy humans: possible role of nuclear factor κB
Ashley E. Walker;
Ashley E. Walker
*Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, U.S.A.
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Rachelle E. Kaplon;
Rachelle E. Kaplon
*Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, U.S.A.
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Gary L. Pierce;
Gary L. Pierce
*Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, U.S.A.
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Molly J. Nowlan;
Molly J. Nowlan
*Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, U.S.A.
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Douglas R. Seals
*Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, U.S.A.
Correspondence: Professor Douglas R. Seals (email [email protected]).
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Publisher: Portland Press Ltd
Received:
January 08 2014
Revision Received:
June 16 2014
Accepted:
June 20 2014
Accepted Manuscript online:
June 20 2014
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2014 Biochemical Society
2014
Clin Sci (Lond) (2014) 127 (11): 645–654.
Article history
Received:
January 08 2014
Revision Received:
June 16 2014
Accepted:
June 20 2014
Accepted Manuscript online:
June 20 2014
Citation
Ashley E. Walker, Rachelle E. Kaplon, Gary L. Pierce, Molly J. Nowlan, Douglas R. Seals; Prevention of age-related endothelial dysfunction by habitual aerobic exercise in healthy humans: possible role of nuclear factor κB. Clin Sci (Lond) 1 December 2014; 127 (11): 645–654. doi: https://doi.org/10.1042/CS20140030
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