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

Abstract

Introduction: Regular aerobic exercise reverses aging‐induced deterioration of arterial stiffness via an increased arterial nitric oxide (NO) production. Concurrently, asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, was decreased by aerobic exercise training. A recent study showed that the NOx/ADMA ratio reflects endothelial function and may be an index of the states of cardiovascular disease. However, whether changes in the NOx/ADMA ratio by aerobic exercise training are associated with a decrease in arterial stiffness in healthy middle‐aged and older male and female adults remains unclear. Purpose: This study aimed to clarify whether the relationship between plasma ADMA and NOx levels affected aerobic exercise training‐induced reduction of arterial stiffness in middle‐aged and older adults. Additionally, we examined whether the effect of AT on circulating ADMA levels differed according to sex. Methods: Thirty‐one healthy middle‐aged and older male and female subjects (male = 13, female = 18, 66.4±1.3 years) participated in the study. The subjects were randomly divided into 2 groups: a training group (n=16 [male = 6 / female = 10], 64.8±2.0 years) and a control group (n=15 [male = 7 / female = 8], 68.1±1.6 years). Subjects in the training group performed the AT program, which consisted of cycling on a leg ergometer at 60‐ 70% of peak oxygen uptake (V(.)O2peak)for 45 min/day, 3 days/week for 8 weeks. Before and after the 8‐week aerobic exercise training intervention, V(.)O2peak, plasma ADMA levels and plasma NOx levels were measured in all subjects. Also, carotid β‐stiffness as an index of arterial stiffness was determined with ultrasonography. Results: Aerobic exercise training significantly increased V(.)O2peak (P<0.05) and decreased carotid b‐stiffness (P<0.01). Moreover, plasma ADMA levels were significantly decreased, and plasma NOx levels and NOx/ADMA ratio were significantly increased by aerobic exercise training (P<0.01). Additionally, no sex differences in aerobic exercise traininginduced changes in circulating ADMA and NOx levels, NOx/ADMA ratio, and carotid β‐stiffness were observed. Furthermore, the aerobic exercise training‐induced increase in circulating ADMA levels was negatively correlated with the increase in circulating NOx levels (r=‐0.414, P<0.05), and aerobic exercise training induced increase in NOx/ADMA ratio was negatively correlated with the decrease in carotid β‐stiffness (r=‐0.514, P<0.01). Conclusion: These results suggest that higher NOx/ADMA ratio affects aerobic exercise training‐induced reduction of arterial stiffness, regardless of sex in middle‐aged and older adults.