B6D2F1 Mice Are a Suitable Model of Oxidative Stress-Mediated Impaired Endothelium-Dependent Dilation With Aging
B6D2F1 Mice Are a Suitable Model of Oxidative Stress-Mediated Impaired Endothelium-Dependent Dilation With Aging
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DOI：
10.1093/gerona/gln049
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发表时间：
2009-01-01
影响因子：
5.1
通讯作者：
Seals, Douglas R.
中科院分区：
文献类型：
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作者：
Lesniewski, Lisa A.;Connell, Melanie L.;Seals, Douglas R.
为了确定B6 D2 F1小鼠是否代表氧化应激介导的内皮依赖性扩张（EDD）随衰老受损的合适模型，对6.9 +/- 0.3和31.9 +/- 0.6个月的小鼠进行了研究。在老年小鼠的离体颈动脉（n = 10-11）和股动脉（n = 10）中，乙酰胆碱（ACh）的EDD分别降低了26%（p <0.001）和12%（p <0.001），老年小鼠全身ACh输注的动脉压降低较小（n = 6-10; p <0.01）。硝基酪氨酸在老年小鼠的主动脉中是显著的（p <0.05，n = 4）。颈动脉中的超氧化物生成更大（p <0.05），TEMPOL恢复了老年小鼠颈动脉和全身的扩张。N-G-硝基-L-精氨酸甲酯（L-NAME）减少年轻小鼠的颈动脉扩张比老年小鼠多，而TEMPOL恢复L-NAME在老年小鼠中的作用。与年轻小鼠相比，老年小鼠的颈动脉硬度增加（p = 0.04）。我们的研究结果提供了第一个全面的证据表明，B6 D2 F1小鼠是一个有用的模型，用于研究一氧化氮依赖性降低，氧化应激相关的EDD和动脉僵硬度随年龄增长的机制。
To determine if B6D2F1 mice represent a suitable model of oxidative stress-mediated impaired endothelium-dependent dilation (EDD) with aging, mice were studied at 6.9 +/- 0.3 and 31.9 +/- 0.6 months. EDD to acetylcholine (ACh) was 26% (p < .001) and 12% (p < .001) lower, respectively, in isolated carotid (n = 10-11) and femoral (n = 10) arteries from older mice, and reductions in arterial pressure to systemic ACh infusion were smaller in older mice (n = 6-10; p < .01). Nitrotyrosine was marked in aorta of older mice (p < .05, n = 4). Superoxide production in carotid arteries was greater (p < .05), and TEMPOL restored dilation in carotid arteries and systemically in older mice. N-G-nitro-L-arginine methyl ester (L-NAME) reduced carotid artery dilation in young more than older mice, whereas TEMPOL restored the effects of L-NAME in older mice. Carotid artery stiffness was increased in older compared with young mice (p = .04). Our results provide the first comprehensive evidence that B6D2F1 mice are a useful model for investigating mechanisms of reduced nitric oxide-dependent, oxidative stress-associated EDD and increased arterial stiffness with aging.