Time course of improvement in novel nitric oxide-regulated hormones in response to exercise training in middle-aged and older adults

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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<0.05) and 8 (P<0.01). Plasma NOx level was gradually elevated during exercise intervention and significantly increased from baseline at weeks 6 (P<0.05) and 8 (P<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<0.01). Additionally, plasma ADMA level was significantly decreased at 8-week intervention (P<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<0.05), adropin (r=0.662, P<0.01), or ADMA (r=−0.483, P<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<0.05) or adropin (r=0.556, P<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.