title: Prevention of age-related endothelial dysfunction by habitual aerobic exercise in healthy humans: possible role of nuclear factor κB.
abstract: 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.
authors.affiliation: *Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, U.S.A.
authors.forename: Ashley E
authors.initials: AE
authors.lastname: Walker
authors.affiliation: *Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, U.S.A.
authors.forename: Rachelle E
authors.initials: RE
authors.lastname: Kaplon
authors.affiliation: *Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, U.S.A.
authors.forename: Gary L
authors.initials: GL
authors.lastname: Pierce
authors.affiliation: *Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, U.S.A.
authors.forename: Molly J
authors.initials: MJ
authors.lastname: Nowlan
authors.affiliation: *Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, U.S.A.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Seals
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001916:Brachial Artery / Q000187:drug effects; D004727:Endothelium / Q000503:physiopathology*; D015444:Exercise; D005260:Female; D006184:Habits; D006801:Humans; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects; D012459:Salicylates / Q000494:pharmacology; D057185:Sedentary Behavior; D015398:Signal Transduction; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014664:Vasodilation / Q000502:physiology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016328:NF-kappa B; D012459:Salicylates; C002744:3-nitrotyrosine; D014443:Tyrosine; C014182:salicylsalicylic acid