TY - JOUR
T1 - Transcriptional basis for exercise limitation in male eNOS-knockout mice with age
T2 - Heart failure and the fetal phenotype
AU - Ojaimi, Caroline
AU - Li, Wei
AU - Kinugawa, Shintaro
AU - Post, Heiner
AU - Csiszar, Anna
AU - Pacher, Pal
AU - Kaley, Gabor
AU - Hintze, Thomas H.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2005/10
Y1 - 2005/10
N2 - 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.
AB - 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.
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U2 - 10.1152/ajpheart.00170.2005
DO - 10.1152/ajpheart.00170.2005
M3 - Article
C2 - 15879487
AN - SCOPUS:25444517274
VL - 289
SP - H1399-H1407
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 0363-6135
IS - 4 58-4
ER -