*Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, U.S.A.
Clin Sci (Lond). 2014 Dec;127(11):645-54. doi: 10.1042/CS20140030.
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.
习惯性的有氧运动可预防与年龄相关的内皮依赖性扩张功能障碍（EDD）。我们假设促炎转录因子核因子 κB（NF-κB）通过久坐的衰老损害 EDD，而习惯性的有氧运动通过 NF-κB 预防这种与年龄相关的 EDD 抑制。为了验证这一假设，我们通过口服水杨酸盐在健康的老年有氧运动训练成年人（OT，n=14，58±2 岁）、老年非运动成年人（ON，n=16，61±1 岁）和年轻非运动对照者（YN，n=8，23±1 岁）中抑制 NF-κB 信号。水杨酸盐降低了 ON 中内皮细胞 NF-κB p65 的表达约 25%（P<0.05），但在 OT 或 YN 中未显著改变表达（P>0.05）。肱动脉血流介导的扩张（FMD）评估的 EDD 通过水杨酸盐在 ON 中得到改善（4.0±0.7%，与安慰剂相比，与水杨酸盐相比，P<0.001），但在 OT 或 YN 中没有因水杨酸盐而改变（OT：7.2±0.7%，与安慰剂相比，与水杨酸盐相比，P>0.05；YN：7.6±0.9%，与安慰剂相比，与水杨酸盐相比，P>0.05）。内皮非依赖性扩张不受任何组的水杨酸盐影响（P>0.05）。在 ON 中，维生素 C 输注在安慰剂期间使 FMD 改善约 30%（P<0.001），但在水杨酸盐期间没有影响（P>0.05）。在 OT 和 YN 中，维生素 C 输注在安慰剂或水杨酸盐期间均未影响 FMD（P>0.05）。水杨酸盐降低了 ON 中内皮细胞硝基酪氨酸含量约 25%，并降低了 NADPH 氧化酶 p47phox 表达约 30%（P<0.05），但在 OT 或 YN 中没有影响（P>0.05）。我们的结果表明，内皮 NF-κB 信号与健康非运动但不进行有氧运动的老年成年人中与氧化应激相关的 EDD 损害有关。这可能是定期有氧运动通过与年龄相关的内皮功能障碍和降低心血管风险的关键机制。
