Time-dependent relationships between exercise training-induced changes in nitric oxide production and hormone regulation

Aerobic exercise training (AT) reduces aging-induced deterioration of arterial stiffness and is associated with arterial nitric oxide (NO) production via changes in apelin and adropin as NO-upregulating hormones, and asymmetric dimethylarginine (ADMA) as a NO-downregulating hormone. However, the time-dependent effects of AT on NO production via NO-regulating hormones remain unclear. This study aimed to determine whether AT-induced changes in the time course of NO production via NO-regulating hormones, participate in the AT-induced improvement in central arterial stiffening with advancing age. Methods: Thirty-three healthy Japanese middle-aged and older subjects (67 ± 1 years) were randomly divided into two groups: AT intervention and sedentary controls. Subjects in the training group completed 8-week of AT. Carotid–femoral pulse wave velocity as an index of central arterial stiffness and plasma nitrate/nitrite levels significantly changed from baseline at weeks 6 ( P < 0.05) and 8 ( P < 0.01). Interestingly, circulating apelin and adropin levels gradually increased during AT intervention and significantly increased from baseline at weeks 4, 6, and 8 ( P < 0.01). Additionally, plasma ADMA levels significantly decreased at 8-week AT intervention ( P < 0.01). These results suggest that AT-induced changes in the time course of NO production via NO-regulating hormones may participate in AT-induced improvements of central arterial stiffening with advancing age. • Differences of time-dependent changes in NO-regulating hormones by exercise occur. • The exercise-induced increase in NO production was regulated by NO-regulating hormones. • Levels of apelin, adropin, and ADMA change with exercise in a time-dependent manner. • NO production occurs in parallel with changes in arterial stiffness in older adults. • NO-regulating hormones may predict exercise-induced increase in NO production.