Transcriptional basis for exercise limitation in male eNOS-knockout mice with age: heart failure and the fetal phenotype
Transcriptional basis for exercise limitation in male eNOS-knockout mice with age: heart failure and the fetal phenotype
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DOI：
10.1152/ajpheart.00170.2005
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发表时间：
2005-10-01
影响因子：
4.8
通讯作者：
Hintze, TH
中科院分区：
文献类型：
--
作者：
Ojaimi, C;Li, W;Hintze, TH
内皮源性一氧化氮（NO）在调节小鼠线粒体O-2消耗(（V)超过dotO(2)）和葡萄糖摄取中起关键作用。本研究的目的是探讨年龄和基因型相关的运动限制在雄性内皮NO合成酶（eNOS）敲除（KO, n=16）和野生型（WT, n=19）小鼠中的机制。在12、14、16、18和21月龄时进行跑步机试验。(V) / dotO(2)、CO2产量、呼吸交换比和最大跑步距离在跑步机上被测定。在dotO(2)上，速度的增加与(V)的增加呈良好的线性相关。在12个月时，KO和WT小鼠之间的差异不显著，但在18个月时差异显著。线性回归显示，在相同的绝对和相对工作量下，KO小鼠消耗更多的O-2，这表明KO小鼠的(V)超过dotO(2)不受NO的抑制。KO小鼠在每个年龄比WT小鼠少30-50%的工作量（工作量=垂直距离x体重）。与WT小鼠相比，KO小鼠完成的工作从12个月时的17 +/- 1.4 m.kg显著减少到21个月时的9.4 +/- 1.7 m.kg。跑步距离从12个月时的334 +/- 27 m显著减少到21个月时的178 +/- 38 m， KO小鼠的最大(V) / dotO(2)、二氧化碳产量和每工作单位的呼吸交换比显著高于WT小鼠。基因阵列显示了21月龄KO小鼠胎儿表型的证据。总之，年龄和基因型相关的运动限制在雄性eNOS-KO小鼠中进行的最大工作和最大跑步距离表明，胎儿表型和年龄与心力衰竭的发生有关。
Endothelium-derived nitric oxide (NO) is pivotal in regulating mitochondrial O-2 consumption ((V)over dotO(2)) and glucose uptake in mice. The aim of this study was to investigate the mechanism of age- and genotype-related exercise limitation in male endothelial NO synthase (eNOS)-knockout (KO, n=16) and wild-type (WT, n=19) mice. Treadmill testing was performed at 12, 14, 16, 18, and 21 mo of age. (V)over dotO(2), CO2 production, respiratory exchange ratio, and maximal running distance were determined during treadmill running. There were good linear correlations for increase of speed with increase of (V)over dotO(2). The difference between KO and WT mice was not significant at 12 mo but was significant at 18 mo. Linear regression showed that KO mice consumed more O-2 at the same absolute and relative workloads, suggesting that (V)over dotO(2) was not inhibited by NO in KO mice. KO mice performed 30-50% less work than WT mice at each age (work=vertical distance x weight). In contrast to WT mice, the work performed by KO mice significantly decreased from 17 +/- 1.4 m.kg at 12 mo to 9.4 +/- 1.7 m.kg at 21 mo. Running distance was significantly decreased from 334 +/- 27 m at 12 mo to 178 +/- 38 m at 21 mo, and maximal (V)over dotO(2), CO2 production, and respiratory exchange ratio per work unit were significantly higher in KO than in WT mice. Gene arrays showed evidence of a fetal phenotype in KO mice at 21 mo. In conclusion, age- and genotype-related exercise limitations in maximal work performed and maximal running distance in male eNOS-KO mice indicated that fetal phenotype and age were related to onset of heart failure.