Short-and long-term fructose feeding alters exercise capacity of rats

To test the hypothesis that high‐fructose (HF) consumption alters exercise capacity, rats were fed a normal, or a HF (60%) diet for 3, 6, 10 and 30 days, and run on a treadmill. Surprisingly, running distance/work was significantly increased in rats fed HF for 3 (HF‐3D) and 6 days, but was decreased in rats of HF‐30D. Shear stressinduced vasodilation (SSID) in plantaris muscle arterioles of HF‐3D rats was significantly greater than that of controls. L‐NAME abolished the difference in SSID between two groups, suggesting an increased NO‐mediated SSID in HF‐3D rats. Upregulation of phospho‐eNOS (p‐eNOS) in skeletal muscles of HF‐3D compared to controls suggests an enhanced eNOS sensitivity to shear stress. However, SSID was significantly reduced in vessels of HF‐30D rats that were hypertensive, showing a weaker inhibitory effect of L‐NAME on the responses and downregulation of phospho‐eNOS. There was an impaired NO‐dependent regulation of myocardial oxygen consumption in HF‐30D rats, which was partially reversed by apocynin. Thus, short‐term HF feeding enhances exercise capacity of rats, due to an increased endothelial sensitivity to shear stress, which promotes tissue perfusion and oxygen utilization. Long‐term HF feeding initiates endothelial dysfunction in a superoxide‐dependent manner, which restrict exercise capacity of rats. (This work was supported by NIH HL‐43023).