l-Arginine enhances aerobic exercise capacity in association with augmented nitric oxide production

We tested whether supplementation with l-arginine can augment aerobic capacity, particularly in conditions where endothelium-derived nitric oxide (EDNO) activity is reduced. Eight-week-old wild-type (E+) and apolipoprotein E-deficient mice (E−) were divided into six groups; two groups (LE+ and LE−) were given l-arginine (6% in drinking water), two were given d-arginine (DE+ and DE−), and two control groups (NE+ and NE−) received no arginine supplementation. At 12–16 wk of age, the mice were treadmill tested, and urine was collected after exercise for determination of EDNO production. NE−mice demonstrated a reduced aerobic capacity compared with NE+ controls [maximal oxygen uptake (V˙o 2 max) of NE− = 110 ± 2 (SE) vs. NE+ = 122 ± 3 ml O2 · min−1 · kg−1, P < 0.001]. This decline in aerobic capacity was associated with a diminished postexercise urinary nitrate excretion. Mice given l-arginine demonstrated an increase in postexercise urinary nitrate excretion and aerobic capacity in both groups (V˙o 2 max of LE−= 120 ± 1 ml O2 · min−1 · kg−1, P < 0.05 vs. NE−;V˙o 2 max of LE+ = 133 ± 4 ml O2 · min−1 · kg−1, P < 0.01 vs. NE+). Mice administered d-arginine demonstrated an intermediate increase in aerobic capacity in both groups. We conclude that administration of l-arginine restores exercise-induced EDNO synthesis and normalizes aerobic capacity in hypercholesterolemic mice. In normal mice, l-arginine enhances exercise-induced EDNO synthesis and aerobic capacity.