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
Authors: Shimomura M , Fujie S , Sanada K , Kajimoto H , Hamaoka T , Iemitsu M 
Published: October 2021

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&lt;0.05) and decreased carotid b-stiffness (P&lt;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&lt;0.01). Additionally, no sex differences in aerobic exercise training-induced 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&lt;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&lt;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.

Funding Acknowledgement
Type of funding sources: Other. Main funding source(s): This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan