Voluntary wheel running restores endothelial function in conduit arteries of old mice: direct evidence for reduced oxidative stress, increased superoxide dismutase activity and down-regulation of NADPH oxidase
Voluntary wheel running restores endothelial function in conduit arteries of old mice: direct evidence for reduced oxidative stress, increased superoxide dismutase activity and down-regulation of NADPH oxidase
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DOI：
10.1113/jphysiol.2009.169771
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发表时间：
2009-07-01
影响因子：
5.5
通讯作者：
Lesniewski, Lisa A.
中科院分区：
文献类型：
--
作者：
Durrant, Jessica R.;Seals, Douglas R.;Lesniewski, Lisa A.
习惯性有氧运动与老年人的内皮依赖性扩张（EDD）增强有关，可能是通过增加一氧化氮生物利用度和减少氧化应激来实现的。然而，所涉及的机制尚不完全清楚。在年轻（6-8 个月）和年老（29-32 个月）笼控小鼠和自愿轮跑 (VR) B6D2F1 小鼠中测量 EDD。与年龄相关的最大颈动脉EDD对乙酰胆碱的减少（74% vs. 96%，P < 0.01）和EDD的一氧化氮（NO）成分（ACh和l-NAME的最大扩张减去单独ACh的最大扩张为-28% vs. -55%，P < 0.01）在旧VR中恢复（EDD：96%，NO：-46%）。硝基酪氨酸是氧化应激的标志物，随着年龄的增长，主动脉中的硝基酪氨酸含量增加，但老年 VR 中的硝基酪氨酸含量明显降低（P < 0.05）。与旧笼对照相比，旧 VR 中主动脉超氧化物歧化酶 (SOD) 活性较高 (P < 0.01)，而 NADPH 氧化酶蛋白表达 (P < 0.01) 和活性 (P = 0.05) 较低。增加 SOD（使用 4-羟基-2,2,6,6-四甲基哌啶 1-氧基）和抑制 NADPH 氧化酶（使用罗布麻素）可改善老笼对照小鼠的 EDD 及其 NO 成分，但不能改善老年 VR 小鼠。 VR 增加了老年小鼠的内皮一氧化氮合酶 (eNOS) 蛋白表达 (P < 0.05) 和激活（Ser1177 磷酸化）(P < 0.05)。 VR 不会影响幼鼠的 EDD。我们的结果表明，自愿有氧运动通过刺激 SOD 抗氧化活性和抑制 NADPH 氧化酶超氧化物产生来抑制氧化应激，从而恢复与年龄相关的 EDD 损失。 eNOS 蛋白和激活的增加也可能有助于运动介导的 NO 生物利用度和 EDD 随着衰老的保持。
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.