Key result
Exercise training increases aortic eNOS expression ~3.4-fold in normal mice but fails in eNOS+/- mice.
Why the study?
Previous data suggested one eNOS gene is sufficient for normal eNOS expression under basal conditions, but it was unknown if this holds during exercise-induced eNOS upregulation.
Does exercise training increase eNOS expression in mice lacking one eNOS gene compared to normal mice?
Does exercise training increase eNOS expression in mice lacking one eNOS gene compared to normal mice?
Effect estimate: 3.4-fold increase in eNOS+/+ mice
p-value: p=<0.002
Regulation of eNOS expression during exercise requires both alleles of the gene, suggesting individuals with eNOS polymorphisms may have impaired vascular adaptation to exercise.
eNOS gene dosage is required for exercise-induced aortic changes in mice; hypothesis-generating for human endothelial adaptations and should not yet change practice.
BACKGROUND: Previous data suggest that 1 endothelial NO synthase (eNOS) gene is sufficient to allow normal expression and function of eNOS under basal conditions. We hypothesized that this might not hold true for conditions known to increase eNOS gene expression, such as exercise. METHODS AND RESULTS: Male mice heterozygous for a disruption of the eNOS gene (eNOS(+/)(-)) and normal C56Bl/6J mice (eNOS(+/+)), 3 to 4 months of age, underwent exercise training for 3 weeks. Nontrained mice were exposed to the exercise environment (noise and vibration of the treadmill) without exercise for an identical period. In eNOS(+/+) mice (n=7), exercise increased aortic eNOS protein expression by 3.4+/-0.4-fold (P<0.002). This was associated with a greater vascular cGMP accumulation on stimulation with acetylcholine (P<0.05). Furthermore, exercise training increased eNOS mRNA (1.78+/-0.4-fold) and protein (1.76+/-0.17-fold) in left ventricular tissue, as determined by competitive reverse transcription-polymerase chain reaction and Western analysis (P<0.05 for both). In striking contrast, exercise had no effect on aortic eNOS expression and cGMP accumulation in eNOS(+/)(-) mice (P>0.05). Thus, although eNOS expression appears to be normal in eNOS(+/)(-) mice under basal conditions, these mice are unable to increase eNOS expression during exercise. CONCLUSIONS: These findings show that regulation of eNOS expression during exercise requires the presence of both alleles of the gene and may have implications for conditions in which polymorphisms of eNOS are present in only 1 allele in humans. These individuals may have a normal vascular reactivity under basal conditions but may be unable to adapt their vascular reactivity in response to exercise training.
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Kojda et al. (2001) studied eNOS expression regulation. Exercise training vs. Nontrained mice exposed to the exercise environment without exercise was evaluated on Aortic eNOS protein expression (3.4-fold increase in eNOS+/+ mice, p=<0.002). Exercise training increased aortic eNOS protein expression by 3.4-fold in normal mice (P<0.002) but had no effect in mice lacking one eNOS gene (P>0.05).
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