Abstract 14257: Endothelial Nitric Oxide (NO) Synthase-Derived NO Plays an Essential Role in the Beneficial Effects of Exercise Training via Activating Skeletal Muscle Mitochondrial Biogenesis
Background: Exercise training (ET) increases exercise capacity associated with the activation of mitochondria biogenesis in the skeletal muscle. Resent studies indicate that endothelial nitric oxide (NO) synthase (eNOS) derived-NO regulates the gene expression involved in the mitochondrial biogenesis. However, it remains unknown whether eNOS-derived NO plays an essential role in the beneficial effects of ET on exercise capacity. Thus, we determined whether eNOS-derived NO could be involved in the enhanced on exercise capacity and skeletal muscle mitochondrial biogenesis by ET using eNOS-deficient mice (eNOS-/-),
Methods: Male C57BL/6J wild type (WT) or eNOS-/- mice were divided either sedentary (SED) or ET, which was performed by swimming training at 90 min/day, 5 days/week, for 5 weeks. Exercise capacity was evaluated by the work and peak oxygen uptake (VO2) in the treadmill test. Muscle mitochondrial functions were assessed by measuring enzymatic activities and gene expression related to respiratory chain and biogenesis.
Results: Exercise capacity was significantly greater in WT + ET (n = 10) than in WT + SED (n = 10) (work 32 ± 1 vs. 26 ± 1 J and peak VΟ2 171 ± 2 vs. 150 ± 3 ml/kg/min, respectively P<0.001). eΝΟS-/- + SED (n = 10) mice had lower exercise capacity and this increase in exercise capacity by ET was ameliorated in eNOS-/- + ET(n = 10) mice (Work 19±1 vs. 19±1 J and peak VΟ2 136 ± 3 vs. 133 ± 2 ml/kg/min). In parallel to exercise capacity, enzymatic activities of citrate synthase and mitochondrial complex I and III, and PGC-1α gene expression in the skeletal muscle were significantly increased in WT + ET compared to WT + SED, which were not observed in eNOS-/- mice. The administrations of AICAR (500 mg/kg/day, n = 8) or resveratorol (400 mg/kg/day, n = 8), both of which activates PGC-1α, significantly increased the exercise capacity in WT mice and the effects of two drugs on exercise capacity could not obtained in eNOS-/- mice.
Conclusion: eNOS-derived NO plays an essential role in the beneficial effects of ET on exercise capacity possibly via activating mitochondrial function and biogenesis in the skeletal muscle.
- © 2012 by American Heart Association, Inc.