Transcriptional basis for exercise limitation in male eNOS-knockout mice with age: Heart failure and the fetal phenotype

Caroline Ojaimi, Wei Li, Shintaro Kinugawa, Heiner Post, Anna Csiszar, Pal Pacher, Gabor Kaley, Thomas H. Hintze

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34 Citations (Scopus)


Endothelium-derived nitric oxide (NO) is pivotal in regulating mitochondrial O2 consumption (V̇O2) 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. V̇O2, CO 2 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 V̇O2 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 V̇O2 was not inhibited by NO in KO mice. KO mice performed 30-50% less work than WT mice at each age (work = vertical distance × 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·O2, CO 2 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.

Original languageEnglish
Pages (from-to)H1399-H1407
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number4 58-4
Publication statusPublished - Oct 2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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