Inhibiting nitric oxide generation during exercise prevents physiologic and biochemical adaptations to exercise in hypercholesterolemic mice

This study investigated the effects of continuously inhibiting nitric oxide (NO) generation during short term exercise on the physiologic parameters; work performance to exhaustion and maximum oxygen uptake (V_O2max)' and on the biochemical parameters; skeletal muscle citrate synthase activity and endothelial cell nitric oxide synthase activity (cNOS). Methods: 15 10 week old female C57BL/6 mice fed a high cholesterol diet were divided into 3 groups; sedentary (SD), exercise (EX) and exercise with L-nitroarginine supplemented drinking water (6mg/100cc). (LNEX). Both exercise groups underwent a 4 week period of 1 hour twice daily treadmill running at a final speed of 22 m/min. Five days before the end of the exercise period, the L-nitroarginine supplementation was discontinued. At the end of the exercise period, V_O2max was determined utilizing a metabolic chamber enclosed treadmill. At sacrifice, hindleg muscles were removed for citrate synthase assay and the abdominal aorta was removed for stimulated NO assay. Results: Inhibiting NO generation during exercise training diminishes the work performance to exhaustion and citrate synthase upregulation while it completely prevents the improvement in V_O2max- Upregulation of cNOS appears unaffected. We conclude that some of the basic adaptations to exercise require normal generation of NO.