Relationship between plasma asymmetric dimethylarginine and nitric oxide levels affects aerobic exercise training-induced reduction of arterial stiffness in middle-aged and older adults

Purpose Aerobic exercise training (AT) reverses aging-induced deterioration of arterial stiffness via increased arterial nitric oxide (NO) production. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, was decreased by AT. However, whether AT-induced changes in ADMA levels are related to changes in nitrite/nitrate (NOx) levels remains unclear. Accordingly, we aimed to clarify whether the relationship between plasma ADMA and NOx levels affected the AT-induced reduction of arterial stiffness in middle-aged and older adults. Methods Thirty-one healthy middle-aged and older male and female subjects (66.4 ± 1.3 years) were randomly divided into two groups: exercise intervention and sedentary controls. Subjects in the training group completed an 8-week AT (60%-70% peak oxygen uptake [VO2peak] for 45 min, 3 days/week). Results AT significantly increased VO2peak (P < 0.05) and decreased carotid β-stiffness (P < 0.01). Moreover, plasma ADMA levels were significantly decreased while plasma NOx levels and NOx/ADMA ratio were significantly increased by AT (P < 0.01). Additionally, no sex differences in AT-induced changes of circulating ADMA and NOx levels, NOx/ADMA ratio, and carotid β-stiffness were observed. Furthermore, the AT-induced increase in circulating ADMA levels was negatively correlated with an increase in circulating NOx levels (r = -0.414, P < 0.05), and the AT-induced increase in NOx/ADMA ratio was negatively correlated with a decrease in carotid β-stiffness (r = -0.514, P < 0.01). Conclusion These results suggest that the increase in circulating NOx with reduction of ADMA elicited by AT is associated with a decrease in arterial stiffness regardless of sex in middle-aged and older adults.