Plasma asymmetric dimethylarginine concentrations are not related to differences in maximal oxygen uptake in endurance trained and untrained men

NEW FINDINGS: What is the central question of this study? Is there an association of plasma concentration of asymmetric dimethylarginine, which is related to exercise capacity in patients with cardiovascular diseases, with oxygen delivery and subsequently exercise capacity in healthy subjects in the absence of the potentially confounding influence of inflammation and oxidative stress? What is the main finding and its importance? Plasma asymmetric dimethylarginine concentrations are not related to exercise capacity in healthy subjects, while O2 delivery in the working skeletal muscle during the maximal graded-exercise test is not associated with any of the l-arginine analogues. ADMA alone does not play a crucial role in local muscle perfusion and in maintaining exercise capacity.

ABSTRACT: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) synthesis that could limit oxygen (O2 ) delivery in the working skeletal muscles by altering endothelium-dependent vasodilatation. Exercise capacity is associated with plasma ADMA concentrations in patients with cardiovascular diseases, but this issue has still not been investigated in healthy subjects. We aimed to determine whether plasma ADMA concentrations were negatively associated with exercise capacity in young healthy male subjects. Ten men with maximal oxygen uptake ( V ̇ O 2 max ) > 65 mL kg-1 min-1 were included in the high exercise capacity group (HI-FIT), and 10 men with V ̇ O 2 max < 45 mL kg-1 min-1 were included in the low exercise capacity group (LO-FIT). Plasma ADMA and other l-arginine analogue concentrations were measured before and after a maximal graded-exercise test by liquid chromatography-tandem mass spectrometry. Microvascular O2 delivery during exercise was estimated through the pattern from the sigmoid model of muscle deoxygenation in the vastus lateralis measured by near infrared spectroscopy. V ̇ O 2 max was 60% higher in the HI-FIT group (median: 70.2 mL kg-1 min-1 ; IQR: 68.0-71.9 mL kg-1 min-1 ) than in the LO-FIT group (median: 43.8 mL kg-1 min-1 ; IQR: 34.8-45.3 mL kg-1 min-1 ). Plasma ADMA concentrations did not differ between the LO-FIT and HI-FIT groups before (0.50 ± 0.06 vs. 0.54 ± 0.07 μmol L-1 , respectively) and after the maximal incremental exercise test (0.49 ± 0.08 vs. 0.55 ± 0.03 μmol L-1 , respectively). There was no significant association of plasma ADMA concentrations with the pattern of local muscle deoxygenation and exercise capacity. Exercise capacity and microvascular O2 delivery are not related to plasma ADMA concentrations in young healthy male subjects. Our findings show that ADMA does not play a crucial role in local muscle perfusion and in maintaining exercise capacity without pathological conditions.