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

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S Fujie ◽  
N Hasegawa ◽  
K Sanada ◽  
T Hamaoka ◽  
J Padilla ◽  
...  

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.

2020 ◽  
Vol 41 (Supplement_1) ◽  
Author(s):  
S Fujie ◽  
N Hasegawa ◽  
K Sanada ◽  
T Hamaoka ◽  
S Maeda ◽  
...  

Abstract Funding Acknowledgements Supported by Grants-in-Aid for Scientific Research (#17H02182, #16K13059, M. Iemitsu; #18J01024, S. Fujie) Introduction Aging is well known to elevate risks of cardiovascular diseases. As a mechanism of these increased risks with aging, a reduction of nitric oxide (NO) production via augmented secretion of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthesis is related. Habitual aerobic exercise has shown to improve secretory unbalance of endothelium-derived regulating factors with aging, such as increase in NO and decrease in ADMA, resulting in the reduction of arterial stiffness. However, the time course of improvement in secretory unbalance of NO and ADMA productions in response to exercise training in middle-aged and older adults remains unclear. Purpose This study aimed to determine the time course of changes in plasma nitrite/nitrate (NOx) and ADMA levels related to exercise-training effects of arterial stiffness 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 NOx and ADMA concentrations 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 ADMA level was significantly decreased at 8-week intervention (P < 0.05). Furthermore, the exercise training-induced reduction in plasma ADMA level was negatively correlated with the change in plasma NOx level before and after the 8-week (r = -0.483, P < 0.05). The exercise training-induced change in plasma ADMA concentration was positively correlated with training-induced change in cfPWV before and after the 8-week (r = 0.633, P < 0.01). Additionally, there was a negative correlation between the changes in plasma NOx level and cfPWV before and after the 8-week (r = -0.642, P < 0.05). Conclusions These results suggest that habitual aerobic exercise can normalize the secretory unbalance of NO and ADMA productions in 6 to 8 weeks, and these balance normalizations may be contributed to the reduction of arterial stiffness in the middle-aged and older adults.


2018 ◽  
Vol 314 (1) ◽  
pp. R94-R101 ◽  
Author(s):  
Natsuki Hasegawa ◽  
Shumpei Fujie ◽  
Naoki Horii ◽  
Masataka Uchida ◽  
Toshiyuki Kurihara ◽  
...  

Adiponectin regulates endothelial nitric oxide synthase in endothelial cells, and body fat loss by aerobic exercise training promotes adiponectin secretion. Recently, C1q/tumor necrosis factor-related proteins (CTRPs) have been identified as novel adipokines and are paralogs of adiponectin, but the association between exercise training-induced reduction of arterial stiffness and circulating CTRPs levels remains unclear. This study aimed to clarify whether the reduction of arterial stiffness in middle-aged and older adults is associated with the change in serum levels of CTRPs induced by exercise training. A total of 52 middle-aged and older participants were randomly divided into two groups: a training group ( n = 26) and a sedentary control group ( n = 26). Participants in the training group completed 8 wk of aerobic exercise training (60–70% peak oxygen uptake for 45 min, 3 days/wk). The reduction of percent whole body fat, abdominal visceral fat area, and carotid-femoral pulse-wave velocity (cfPWV) was significantly greater in the training group than in the control group ( P < 0.05). Moreover, the increase in serum adiponectin, CTRP3, and CTRP5 from baseline to 8 wk was significantly higher in the training group compared with the control group ( P < 0.05). Additionally, the training-induced change in cfPWV was negatively correlated with the training-induced change in serum adiponectin, CTRP3, and CTRP5 levels ( r = −0.51, r = −0.48, r = −0.42, respectively, P < 0.05), and increased plasma nitrite/nitrate level by exercise training was correlated only with adiponectin levels ( r = 0.41, P < 0.05). These results suggest that the exercise training-induced increase in serum CTRPs levels may be associated with the reduction of arterial stiffness in middle-aged and older adults.


Aging ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 1201-1212 ◽  
Author(s):  
Shumpei Fujie ◽  
Natsuki Hasegawa ◽  
Kiyoshi Sanada ◽  
Takafumi Hamaoka ◽  
Seiji Maeda ◽  
...  

Author(s):  
Nobuhiko AKAZAWA ◽  
Koichiro TANAHASHI ◽  
Keisei KOSAKI ◽  
Satoshi OIKAWA ◽  
Hiroshi KUMAGAI ◽  
...  

2007 ◽  
Vol 293 (3) ◽  
pp. H1466-H1472 ◽  
Author(s):  
Jun Sugawara ◽  
Hidehiko Komine ◽  
Koichiro Hayashi ◽  
Mutsuko Yoshizawa ◽  
Takeshi Otsuki ◽  
...  

Endurance training improves endothelium-dependent vasodilation, yet it does not increase basal blood flow in the legs. We determined the effects of a 3-mo aerobic exercise intervention on basal leg blood flow and α-adrenergic vasoconstriction and nitric oxide (NO) release in seven apparently healthy middle-aged and older adults (60 ± 3 yr). Basal femoral artery blood flow (via Doppler ultrasound) (pretraining: 354 ± 29; posttraining: 335 ± 34 ml/min) and vascular conductance did not change significantly with the exercise training. Before the exercise intervention, femoral artery blood flow increased 32 ± 16% with systemic α-adrenergic blockade (with phentolamine) ( P < 0.05), and the addition of nitric oxide synthase (NOS) inhibition using NG-monomethyl-l-arginine (l-NMMA) did not affect femoral artery blood flow. After training was completed, femoral artery blood flow increased 47 ± 7% with α-adrenergic blockade ( P < 0.01) and then decreased 18 ± 7% with the subsequent administration of l-NMMA ( P < 0.05). Leg vascular conductance showed a greater α-adrenergic blockade-induced vasodilation (+1.7 ± 0.5 to +3.0 ± 0.5 units, P < 0.05) as well as NOS inhibition-induced vasoconstriction (−0.8 ± 0.4 to −2.7 ± 0.7 units, P < 0.05) after the exercise intervention. Resting plasma norepinephrine concentration significantly increased after the training. These results suggest that regular aerobic exercise training enhances NO bioavailability in middle-aged and older adults and that basal limb blood flow does not change with exercise training because of the contrasting influences of sympathetic nervous system activity and endothelium-derived vasodilation on the vasculature.


2015 ◽  
Vol 309 (10) ◽  
pp. H1642-H1647 ◽  
Author(s):  
Shumpei Fujie ◽  
Natsuki Hasegawa ◽  
Koji Sato ◽  
Satoshi Fujita ◽  
Kiyoshi Sanada ◽  
...  

Aging-induced arterial stiffening is reduced by aerobic exercise training, and elevated production of nitric oxide (NO) participates in this effect. Adropin is a regulator of endothelial NO synthase and NO release, and circulating adropin level decreases with age. However, the effect of habitual aerobic exercise on circulating adropin levels in healthy middle-aged and older adults remains unclear. We sought to determine whether serum adropin level is associated with exercise training-induced changes in arterial stiffness. First, in a cross-sectional study, we investigated the association between serum adropin level and both arterial stiffness and cardiorespiratory fitness in 80 healthy middle-aged and older subjects (65.6 ± 0.9 yr). Second, in an intervention study, we examined the effects of 8-wk aerobic exercise training on serum adropin level and arterial stiffness in 40 healthy middle-aged and older subjects (67.3 ± 1.0 yr) divided into two groups: aerobic exercise training and sedentary controls. In the cross-sectional study, serum adropin level was negatively correlated with carotid β-stiffness ( r = −0.437, P < 0.001) and positively correlated with plasma NOx level ( r = 0.493, P < 0.001) and cardiorespiratory fitness ( r = 0.457, P < 0.001). Serum adropin levels were elevated after the 8-wk aerobic exercise training intervention, and training-induced changes in serum adropin level were correlated with training-induced changes in carotid β-stiffness ( r = −0.399, P < 0.05) and plasma NOx level ( r = 0.623, P < 0.001). Thus the increase in adropin may participate in the exercise-induced reduction of arterial stiffness.


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