Time course of improvement in novel nitric oxide-regulated hormones in response to exercise training in middle-aged and older adults
Authors: Fujie S , Hasegawa N , Sanada K , Hamaoka T , Padilla J , Martinez-Lemus L.A , Maeda S , Iemitsu M 
Published: November 2020

Abstract

Introduction
Cardiovascular disease risk augments with advance of age. The mechanism of the increased cardiovascular disease risk by aging is related to attenuation of arterial function via endothelium-derived relaxing factor, such as nitric oxide (NO). Recently, apelin and adropin have identified as NO-upregulated hormones, whereas augmented secretion of asymmetric dimethylarginine (ADMA) have identified as NO-downregulated hormones. However, the effects of exercise training-induced changes in NO-regulated hormones on the reduction of arterial stiffness via NO productions remain unclear.

Purpose
This study aimed to determine the time-dependent changes in NO-regulated hormones related to exercise-training effects of arterial stiffness via NO productions in healthy middle-aged and older adults.

Methods
Thirty-two Japanese healthy middle-aged and older subjects (67±1 years) were randomly divided into two groups: exercise intervention and sedentary controls. Subjects in the training group completed 8-week of aerobic exercise training (60–70% peak oxygen uptake [VO2peak] for 45 min, 3 days/week). We evaluated plasma nitrite/nitrate (NOx), apelin, and ADMA levels, serum apelin level and carotid-femoral pulse wave velocity (cfPWV) as an index of arterial stiffness, measured every 2 weeks for 8-week in the training group.

Results
cfPWV was gradually declined from baseline to 8-week and significantly decreased from baseline at weeks 6 (P&lt;0.05) and 8 (P&lt;0.01). Plasma NOx level was gradually elevated during exercise intervention and significantly increased from baseline at weeks 6 (P&lt;0.05) and 8 (P&lt;0.01). Interestingly, plasma apelin and serum adropin levels were gradually elevated during exercise intervention and significantly increased from baseline at weeks 4, 6 and 8 (each P&lt;0.01). Additionally, plasma ADMA level was significantly decreased at 8-week intervention (P&lt;0.01). Furthermore, the exercise training-induced increase in plasma NOx level was significantly correlated with the changes in circulating apelin (r=0.505, P&lt;0.05), adropin (r=0.662, P&lt;0.01), or ADMA (r=−0.483, P&lt;0.05) levels before and after the 8-week. The exercise training-induced increase in plasma NOx level was significantly correlated with training-induced changes in circulating apelin (r=0.483, P&lt;0.05) or adropin (r=0.556, P&lt;0.05) before and after the 6-week.

Conclusions
These results suggest that the NO-upregulated hormones (apelin and adropin) were increased at the early stage of exercise training intervention and NO-downregulated hormone (ADMA) was decreased at the late stage of exercise training intervention, and these changes in NO-regulated hormones may be contributed to the reduction of arterial stiffness in the middle-aged and older adults.

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.