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 (VO_{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 (VO_{2 max} of LE^- = 120 ± 1 ml O₂ · min^-1 · kg^-1, P < 0.05 vs. NE^-; VO_{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.