Lesniewski Lisa A, Connell Melanie L, Durrant Jessica R, Folian Brian J, Anderson Martin C, Donato Anthony J, Seals Douglas R
Department of Integrative Physiology, University of Colorado at Boulder, 80309, USA.
J Gerontol A Biol Sci Med Sci. 2009 Jan;64(1):9-20. doi: 10.1093/gerona/gln049. Epub 2009 Feb 10.
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.
为了确定B6D2F1小鼠是否代表了一种因衰老导致氧化应激介导的内皮依赖性舒张功能受损（EDD）的合适模型，研究人员对6.9±0.3个月和31.9±0.6个月的小鼠进行了研究。在老年小鼠分离的颈动脉（n = 10 - 11）和股动脉（n = 10）中，对乙酰胆碱（ACh）的EDD分别降低了26%（p <.001）和12%（p <.001），并且老年小鼠（n = 6 - 10；p <.01）对全身注射ACh时动脉压的降低幅度较小。老年小鼠主动脉中硝基酪氨酸标记明显（p <.05，n = 4）。颈动脉中超氧化物的产生更多（p <.05），TEMPOL可恢复老年小鼠颈动脉和全身的舒张功能。N（G）-硝基-L-精氨酸甲酯（L-NAME）对年轻小鼠颈动脉舒张功能的降低作用比对老年小鼠更明显，而TEMPOL可恢复L-NAME对老年小鼠的作用。与年轻小鼠相比，老年小鼠颈动脉僵硬度增加（p =.04）。我们的结果首次提供了全面的证据，表明B6D2F1小鼠是研究一氧化氮依赖性、氧化应激相关的EDD降低和衰老导致动脉僵硬度增加机制的有用模型。
