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

Abstract

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.