Hisashi Naito

Juntendo University, Edo, Tōkyō, Japan

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Publications (124)390.86 Total impact

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    ABSTRACT: Voluntary exercise can ameliorate insulin resistance. The underlying mechanism, however, remains to be elucidated. We previously demonstrated that inducible nitric oxide synthase (iNOS) in the liver plays an important role in hepatic insulin resistance in the setting of obesity. In this study, we tried to verify our hypothesis that voluntary exercise improves insulin resistance by reducing the expression of iNOS and subsequent S-nitrosylation of key molecules of glucose metabolism in the liver. Twenty-one Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type 2 diabetes mellitus, and 18 non-diabetic control Long-Evans Tokushima Otsuka (LETO) rats were randomly assigned to a sedentary group or exercise group subjected to voluntary wheel running for 20 weeks. The voluntary exercise significantly reduced the fasting blood glucose and HOMA-IR in the OLETF rats. In addition, the exercise decreased the amount of iNOS mRNA in the liver in the OLETF rats. Moreover, exercise reduced the levels of S-nitrosylated Akt in the liver, which were increased in the OLETF rats, to those observed in the LETO rats. These findings support our hypothesis that voluntary exercise improves insulin resistance, at least partly, by suppressing the iNOS expression and subsequent S-nitrosylation of Akt, a key molecule of the signal transduction pathways in glucose metabolism in the liver.
    PLoS ONE 07/2015; 10(7):e0132029. DOI:10.1371/journal.pone.0132029 · 3.23 Impact Factor
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    ABSTRACT: Skeletal muscles are composed of two major muscle fiber types: slow-twitch oxidative fibers and fast-twitch glycolytic fibers. The proteins in these muscle fibers are known to differ in their expression, relative abundance, and post-translational modifications. In this study, we report a previously unreported post-translational modification of α-skeletal muscle actin in the skeletal muscles of adult male F344 rats in vivo. Using two-dimensional electrophoresis (2D-PAGE), we first examined the differences in the protein expression profiles between the soleus and plantaris muscles. We found higher intensity protein spots at approximately 60 kDa and pH 9 on 2D-PAGE for the soleus muscle compared with the plantaris muscle. These spots were identified as α-skeletal muscle actin by liquid chromatography-nanoelectrospray ionization-tandem mass spectrometry and western blot analyses. In addition, we found that the 60 kDa α-skeletal muscle actin is modified by small ubiquitin-like modifier (SUMO) 1, using 2D-PAGE and western blot analyses. Furthermore, we found that α-skeletal muscle actin with larger molecular weight was localized in the nuclear and cytosol of the skeletal muscle, but not in the myofibrillar fraction by the combination of subcellular fractionation and western blot analyses. These results suggest that α-skeletal muscle actin is modified by SUMO-1 in the skeletal muscles, localized in nuclear and cytosolic fractions, and the extent of this modification is much higher in the slow muscles than in the fast muscles. This is the first study to show the presence of SUMOylated actin in animal tissues.
    Molecular and Cellular Biochemistry 07/2015; DOI:10.1007/s11010-015-2512-1 · 2.39 Impact Factor
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    ABSTRACT: Low-load voluntary exercise can induce muscle hypertrophy and strength gain when combined with blood flow restriction (BFR) in working muscles. However, it is unknown whether such hypertrophy and strength gain can be induced by involuntary muscle contractions triggered via low-intensity neuromuscular electrical stimulation (NMES), combined with BFR. The purpose of this article was to investigate whether low-intensity NMES combined with BFR could elicit muscle hypertrophy and strength gain in the quadriceps. Eight untrained young males (means ± SEs; age 26.2±0.7 years, height 1.74±0.02 m, body weight 71.4±4.8 kg) received 23 min of unilateral low-intensity (5-10% of maximal voluntary contraction) NMES, twice per day, 5 days per week, for 2 weeks, with treatment of one leg being combined with BFR (NMES-BFR) and the other leg receiving NMES alone (NMES-CON). Quadriceps muscle thickness (MT) and isometric and isokinetic strength were measured before and every week throughout the training and detraining periods. In NMES-BFR legs, MT increased after 2 weeks of training (+3.9%) and decreased after 2 weeks of detraining (-3.0%). NMES-BFR training also increased maximal knee extension strength in isometric (+14.2%) and isokinetic (+7.0% at 90°/s, +8.3% at 180°/s) voluntary contractions. In addition, maximal isometric strength decreased (-6.8%), whereas no large fall (-1.9% at 90°/s, -0.6% at 180°/s) in isokinetic maximal strength was evident after 2 weeks of detraining. In NMES-CON legs, no prominent change was observed; there was a negligible effect on isometric strength. Low- intensity NMES combined with BFR induces muscle hypertrophy and strength gain in untrained young males.
    Medicine and science in sports and exercise 06/2015; DOI:10.1249/MSS.0000000000000722 · 4.46 Impact Factor
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  • Akihiro Sakamoto · Hisashi Naito · Chin Moi Chow
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    ABSTRACT: Hyperventilation, implemented during recovery of repeated maximal sprints, has been shown to attenuate performance decrement. This study evaluated the effects of hyperventilation, using strength exercises, on muscle torque output and EMG amplitude. Fifteen power-trained athletes underwent maximal isokinetic knee extensions consisting of 12 repetitions × 8 sets at 60°/s and 25 repetitions × 8 sets at 300°/s. The inter-set interval was 40 s for both speeds. For the control condition, subjects breathed spontaneously during the interval period. For the hyperventilation condition, subjects hyperventilated for 30 s before each exercise set (50 breaths/min, PETCO2: 20-25 mmHg). EMG was recorded from the vastus medialis and lateralis muscles to calculate the mean amplitude for each contraction. Hyperventilation increased blood pH by 0.065-0.081 and lowered PCO2 by 8.3-10.3 mmHg from the control values (P < 0.001). Peak torque declined with repetition and set numbers for both speeds (P < 0.001), but the declining patterns were similar between conditions. A significant, but small enhancement in peak torque was observed with hyperventilation at 60°/s during the initial repetition phase of the first (P = 0.032) and fourth sets (P = 0.040). EMG amplitude also declined with set number (P < 0.001) for both speeds and muscles, which was, however, not attenuated by hyperventilation. Despite a minor ergogenic effect in peak torque at 60°/s, hyperventilation was not effective in attenuating the decrement in torque output at 300°/s and decrement in EMG amplitude at both speeds during repeated sets of maximal isokinetic knee extensions.
    Arbeitsphysiologie 02/2015; 115(7). DOI:10.1007/s00421-015-3134-8 · 2.30 Impact Factor
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    ABSTRACT: This paper reviews the existing literature about muscle hypertrophy resulting from various types of training to document the significance of mechanical and metabolic stresses, and to challenge the conventional ideas of achieving hypertrophy that exclusively rely on highload resistance training. Low-load resistance training can induce comparable hypertrophy to that of high-load resistance training when each bout or set is performed until lifting failure. This is attributable to the greater exercise volume and metabolic stress achieved with low-load exercise at lifting failure, which, however, results in a prolonged exercise bout. Endurance exercises (walking and cycling) at moderate intensity are also capable of eliciting muscle hypertrophy, but at much slower rates (months rather than weeks) in limited muscle or age groups. Blood flow restriction (BFR) in working muscles, however, accelerates the development of metabolic fatigue, alleviating the time consuming issue associated with low-load or endurance training. These alternative training methods, however, cannot completely replace conventional high-load resistance training, which provides superior strength gain as well as performance improvement even for trained individuals. The alternative approaches, therefore, may be considered for those who are less enthusiastic or under certain medical conditions, or who have limited or no access to proper equipment. However, people should be aware that low-load resistance training or endurance training entails substantial effort and/or discomfort at lifting failure or with BFR. Understanding the advantages and disadvantages of each method will help in assigning the most suitable training program for each client’s goals and needs.
    Tairyoku kagaku. Japanese journal of physical fitness and sports medicine 02/2015; 4(1):43-51. DOI:10.7600/jpfsm.4.43 · 0.08 Impact Factor
  • Eisuke Hiruma · Shizuo Katamoto · Hisashi Naito
    01/2015; 2(1). DOI:10.5935/MedicalExpress.2015.01.05
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    ABSTRACT: Background The aim of this study is to investigate the independent and joint effects of cardiorespiratory fitness (CRF) and body mass index (BMI) on cancer mortality in a low body mass index population. Methods We evaluated CRF and BMI in relation to cancer mortality in 8760 Japanese men. The median BMI was 22.6 kg/m2 (IQR: 21.0-24.3). The mean follow-up period was more than 20 years. Hazard ratios and 95% CI were obtained using a Cox proportional hazards model while adjusting for several confounding factors. Results Using the 2nd tertile of BMI (21.6-23.6 kg/m2) as reference, hazard ratios and 95% CI for the lowest tertile of BMI (18.5-21.5) were 1.26 (0.87–1.81), and 0.92 (0.64–1.34) for the highest tertile (23.7-37.4). Using the lowest tertile of CRF as reference, hazard ratios and 95% CIs for 2nd and highest tertiles of CRF were 0.78 (0.55–1.10) and 0.59 (0.40–0.88). We further calculated hazard ratios according to groups of men cross-tabulated by tertiles of CRF and BMI. Among men in the second tertile of BMI, those belonging to the lowest CRF tertile had a 53% lower risk of cancer mortality compared to those in the lowest CRF tertile (hazard ratio: 0.47, 95% CI: 0.23-0.97). Among those in the highest BMI tertile, the corresponding hazard ratio was 0.54 (0.25-1.17). Conclusion These results suggest that high CRF is associated with lower cancer mortality in a Japanese population of men with low average BMI.
    BMC Public Health 09/2014; 14(1):1012. DOI:10.1186/1471-2458-14-1012 · 2.32 Impact Factor
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    ABSTRACT: Mechanical ventilation (MV) is a life-saving intervention in patients who are incapable of maintaining adequate pulmonary gas exchange due to respiratory failure or other disorders. However, prolonged MV is associated with the development of respiratory muscle weakness. We hypothesized that a single exposure to whole-body heat stress would increase diaphragm expression of heat shock protein 72 (HSP72) and that this treatment would protect against MV-induced diaphragmatic atrophy. Adult male Wistar rats (n = 38) were randomly assigned to one of four groups: an acutely anesthetized control group (CON) with no MV; 12-h controlled MV group (CMV); 1-h whole-body heat stress (HS); or 1-h whole-body heat stress 24 h prior to 12-h controlled MV (HSMV). Compared to CON animals, diaphragmatic HSP72 expression increased significantly in the HS and HSMV groups (P < 0.05). Prolonged MV resulted in significant atrophy of type I, type IIa, and type IIx fibers in the costal diaphragm (P < 0.05). Whole-body heat stress attenuated this effect. In contrast, heat stress did not protect against MV-induced diaphragm contractile dysfunction. The mechanisms responsible for this heat stress-induced protection remain unclear, but may be linked to increased expression of HSP72 in the diaphragm.
    Journal of Applied Physiology 07/2014; 117(5). DOI:10.1152/japplphysiol.00170.2014 · 3.43 Impact Factor
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    ABSTRACT: Purpose Body weight in young growing and young adult animals was reduced by a high dietary density of whey protein concentrate; however, it is unclear whether dietary proteins similarly affect body weight in aging animals. Here, we examined whether whey protein or whey peptide ingestion suppressed body fat accumulation and affected protein expression and phosphorylation in skeletal muscle in aging mice. Methods Twenty-six male senescence-accelerated mouse prone 6 (SAMP6) mice were assigned randomly to three dietary treatment groups: 18.7 % casein control (CON), 18.7 % whey protein (WPR), and 18.7 % whey peptide (WPE). After 28 weeks of treatment, skeletal tissues were dissected and weighed for analysis. Western blotting was performed to examine the expression of AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), and adipose triglyceride lipase (ATGL) in quadriceps muscles. Results Body (CON: 47.6 ± 2.2 g, WPR: 48.2 ± 2.7 g, WPE: 38.3 ± 2.0 g) and relative white adipose tissue (CON: 38.5 ± 3.5 mg/g, WPR: 43.8 ± 4.0 mg/g, WPE: 21.1 ± 4.4 mg/g) weights were lower in the WPE group compared with the other two groups (p p AMPK (WPR: 1.03 ± 0.11, WPE: 1.36 ± 0.12; fold change from control) and ACC (WPR: 1.08 ± 0.07, WPE: 1.18 ± 0.05; fold change from control) in WPE was higher than in CON (p Conclusions These data suggest that a normal (or moderate excess) dietary density of whey peptide attenuates body fat accumulation via upregulation of fatty acid oxidation in skeletal muscle in aging mice.
    European Journal of Nutrition 07/2014; 54(4). DOI:10.1007/s00394-014-0736-6 · 3.84 Impact Factor
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    ABSTRACT: Context: Intramyocellular lipid (IMCL) accumulation is observed in both insulin-resistant subjects and insulin-sensitive endurance athletes (athlete's paradox). We hypothesized that the expression pattern of fatty acid transporters may influence oxidative capacity and determine the association between IMCL and insulin resistance. Objective: To investigate the muscle expression of fatty acid transporters and their function related to insulin sensitivity in IMCL-accumulated subjects. Design and Setting: The study subjects were 36 non-obese healthy men. Their IMCL levels were measured by (1)H-magnetic resonance spectroscopy and their insulin sensitivity was evaluated by steady state glucose infusion rate (GIR) during euglycemic-hyperinsulinemic clamp. Gene expression levels in the vastus lateralis were evaluated by qRT-PCR. We compared the clinical phenotypes and the expression levels of genes involved in lipid metabolism in skeletal muscle between IMCL-accumulated high-GIR (H-GIR) subjects (n = 8) and low-GIR (L-GIR) subjects (n = 9). The functions of candidate fatty acid transporters were determined by in vitro analyses. Results: Compared with the L-GIR group, body fat was lower and maximum oxygen uptake was higher in the H-GIR group. Several lipid oxidation genes in muscle were up-regulated in the H-GIR group, and this was associated with increased expression of higher plasma membrane-associated fatty acid-binding protein (FABPpm) and decreased expression of fatty acid transport protein (FATP)-1. Overexpression of FABPpm in C2C12 myotubes increased fatty acid oxidation coupled with the elevated expression of genes related to fatty acid oxidation. These changes were not observed in FATP1 overexpressed myotubes. Conclusions: Differences in the gene expression of fatty acid transporters may, at least in part, affect insulin sensitivity in IMCL-accumulated non-obese men.
    Journal of Clinical Endocrinology &amp Metabolism 06/2014; 99(9):jc20141896. DOI:10.1210/jc.2014-1896 · 6.31 Impact Factor
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    ABSTRACT: Walking combined with blood flow reduction (BFR-walk) elicits muscle hypertrophy. However, the skeletal muscle intracellular signaling behind this response is currently unknown. To investigate the effects of BFR-walk on mechanistic target of rapamycin (mTOR) and mitogen-activated protein kinase (MAPK) signaling pathways in young men. Six young men performed 20 minutes of treadmill walking at 55 % of their predetermined maximum oxygen uptake. A pressure cuff belt was applied to the most proximal thigh of only one leg (BFR-Leg, external compression was 240 mmHg) whereas the other leg (CON-Leg) was without BFR during walking. Muscle biopsies were taken from the vastus lateralis of the CON-Leg before exercise and in both legs 3 hours after exercise. Erk1/2 phosphorylation levels were significantly (p<0.05) increased after exercise in both legs, however, only the BFR-Leg saw an increased phosphorylation of p38. For mTOR signaling, there were no changes in Akt, mTOR, or S6K1 phosphorylation levels before or after walking. However, eEF2 phosphorylation level was significantly (p<0.05) lower for the BFR-Leg 3 hours after walking compared with CON-Leg. BFR-walk exercise may activate some intracellular signaling cascades that are associated with muscle hypertrophy in young men. This article is protected by copyright. All rights reserved.
    Acta Physiologica 01/2014; 211(1). DOI:10.1111/apha.12243 · 4.25 Impact Factor
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    ABSTRACT: Protein ingestion after resistance exercise increases muscle protein synthesis (MPS) in a dose-dependent manner. However, the molecular mechanism(s) for the dose-dependency of MPS remains unclear. This study aimed to determine the dose response of mammalian target of rapamycin (mTOR) signaling in muscle with ingestion of protein after resistance exercise. Fifteen male subjects performed four sets of six unilateral isokinetic concentric knee extensions. Immediately after exercise, eight subjects consumed water only. The other seven subjects, in a randomized-order crossover design, took either a 10 [3.6 g essential amino acids (EAA)] or 20 g (7.1 g EAA) solution of whey protein. Muscle biopsies from the vastus lateralis muscle were taken 30 min before and 1 h after resistance exercise. Phosphorylation of Akt (Ser473), mTOR (Ser2448), 4E-BP1 (Thr37/46), and S6K1 (Thr389) was measured by western blotting. Concentric knee extension exercise alone did not increase phosphorylation of Akt and mTOR 1 h after exercise, but ingesting protein after exercise significantly increased the phosphorylation of Akt and mTOR in a dose-dependent manner (P < 0.05). 4E-BP1 phosphorylation significantly decreased after resistance exercise (P < 0.05), but subjects who took 10 or 20 g of protein after exercise showed increased 4E-BP1 from post-exercise dephosphorylation (P < 0.05). S6K1 phosphorylation significantly increased after resistance exercise (P < 0.05), and 20 g of protein further increased S6K1 phosphorylation compared with ingestion of 10 g (P < 0.05). These findings suggest that whey protein intake after resistance exercise activates mTOR signaling in a dose-dependent manner in untrained men.
    Arbeitsphysiologie 01/2014; 114(4). DOI:10.1007/s00421-013-2812-7 · 2.30 Impact Factor
  • Journal of Science and Medicine in Sport 12/2013; 16:e36. DOI:10.1016/j.jsams.2013.10.085 · 3.08 Impact Factor
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  • Akihiro Sakamoto · Hisashi Naito · Chin-Moi Chow
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    ABSTRACT: Repeated high intensity sprints incur substantial anaerobic metabolic challenges and create an acidic muscle milieu that is unfavorable for subsequent performance. Hyperventilation, resulting in respiratory alkalosis, acts as a compensatory mechanism for metabolic acidosis. This study tested the hypothesis that hyperventilation performed during recovery intervals would attenuate performance decrement in repeated sprint pedaling. Thirteen male university athletes performed ten sets of 10 s maximal pedaling on a cycle ergometer with a 60 s recovery between sets under control (spontaneous breathing) and hyperventilation conditions in a crossover, counter-balanced manner. Pedaling load (kp) was set at 0.075 × body mass. Peak and mean power outputs were documented for each set to compare performance decrements over 10 sets between conditions. Hyperventilation (60 breaths/min and PETCO2 maintained at 20-25 mmHg) was performed 30 s before each sprint set. This intervention successfully increased blood pH by 0.03-0.07 but lowered PCO2 by 1.2-8.4 mmHg throughout exercise (P < 0.001). The peak and mean power outputs, and blood [La] accumulation were not significantly different between the conditions. However, a significant condition × time interaction existed for peak power (P = 0.035) and mean power (P = 0.023), demonstrating an attenuation in power decrement in later sprint sets with hyperventilation. In conclusion, hyperventilation implemented during recovery intervals of repeated sprint pedaling attenuated performance decrements in later exercise bouts that was associated with substantial metabolic acidosis. The practical implication is that hyperventilation may have a strategic role for enhancing training effectiveness and may give an edge in performance outcomes.
    The Journal of Strength and Conditioning Research 07/2013; 28(4). DOI:10.1519/JSC.0b013e3182a1fe5c · 1.86 Impact Factor
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    ABSTRACT: AIM: It is well known that various stimuli, such as mechanical stress and nutrients, induce muscle hypertrophy thorough the Akt/mTOR signaling pathway, which is a key mediator of protein synthesis and hypertrophy in skeletal muscle. It was recently reported that heat stress also induces an increase in muscle weight and muscle protein content. In addition, heat stress enhances Akt/mTOR signaling after one bout of resistance exercise. However, it remains unclear whether increased temperature itself stimulates the Akt/mTOR signaling pathway. METHODS: Forty-two male Wistar rats (279.5 ± 1.2 g) were divided into a control group (CON) or one of five thermal stress groups at 37, 38, 39, 40, or 41°C (n = 7 each group). After overnight fasting, both legs were immersed in different temperatures of hot water for 30 min under sodium pentobarbital anesthesia. The soleus and plantaris muscles were immediately removed from both legs after the thermal stress. RESULTS: The phosphorylation of mTOR or 4E-BP1 and heat shock protein (HSP) expression levels were similar among groups in both the soleus and plantaris muscles. However, Akt and p70S6K phosphorylation significantly increased at 41°C in the soleus and plantaris muscles. Moreover, we observed a temperature-dependent increase in Akt and p70S6K activation in both muscles. CONCLUSION: Our data indicate that the altered temperature increased phosphorylation in a temperature-dependent manner in rat skeletal muscle and may itself be a key stimulator of Akt/mTOR signaling. © 2012 The AuthorsActa Physiologica © 2012 Scandinavian Physiological Society.
    Acta Physiologica 11/2012; 207(2). DOI:10.1111/apha.12040 · 4.25 Impact Factor
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    ABSTRACT: The objective of this study was to investigate the factors affecting ball velocity at the final instant of the impact phase (t1) in full instep soccer kicking. Five experienced male university soccer players performed maximal full instep kicks for various foot impact points using a one-step approach. The kicking motions were captured two dimensionally by a high-speed camera at 2,500 fps. The theoretical equation of the ball velocity at t1 given in the article was derived based on the impact dynamics theory. The validity of the theoretical equation was verified by comparing the theoretical relationship between the impact point and the ball velocity with the experimental one. Using this theoretical equation, the relationship between the impact point and the ball velocity was simulated. The simulation results indicated that the ball velocity is more strongly affected by the foot velocity at the initial instant of the impact phase than by other factors. The simulation results also indicated that decreasing the ankle joint reaction force during ball impact shifts the impact point that produces the greatest ball velocity to the toe side and decreasing the ankle joint torque during ball impact shifts the impact point that produces the greatest ball velocity to the ankle side.
    Journal of applied biomechanics 07/2012; 28(3):258-70. · 0.90 Impact Factor
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    ABSTRACT: We examined the effects of high-intensity resistance training (HIT) and low-intensity blood flow-restricted (LI-BFR) resistance training on carotid arterial compliance. Nineteen young men were randomly divided into HIT (n = 9) or LI-BFR (n = 10) groups. The HIT and LI-BFR groups performed 75 and 30 %, respectively, of one-repetition maximum (1-RM) bench press exercise, 3 days per week for 6 weeks. During the training sessions, the LI-BFR group wore elastic cuffs around the most proximal region of both arms. Muscle cross-sectional area (CSA), 1-RM strength, and carotid arterial compliance were measured before and 3 days after the final training session. Acute changes in systolic arterial pressure (SAP), plasma endothelin-1 (ET-1), nitrite/nitrate (NOx), and noradrenalin concentrations were also measured during and after a bout of training session. The training led to significant increases (P < 0.01) in bench press 1-RM and arm and chest muscle CSA in the two training groups. Carotid arterial compliance decreased significantly (P < 0.05) in the HIT group, but not in the LI-BFR group. There was a significant correlation (r = -0.533, P < 0.05) between the change in carotid arterial compliance and the acute change in SAP during training sessions; however, ET-1 and NOx did not correlate with carotid arterial compliance. Our results suggest that muscle CSA and strength increased following 6 weeks of both HIT and LI-BFR training. However, carotid arterial compliance decreased in only the HIT group, and the changes were correlated with SAP elevations during exercise sessions.
    Arbeitsphysiologie 05/2012; 113(1). DOI:10.1007/s00421-012-2422-9 · 2.30 Impact Factor

Publication Stats

2k Citations
390.86 Total Impact Points

Institutions

  • 2001–2014
    • Juntendo University
      • • Institute of Health and Sports Science and Medicine
      • • Department of Health Science
      • • Graduate School of Health and Sports Science
      • • Department of Sports Science
      Edo, Tōkyō, Japan
  • 2007
    • Yamaguchi University
      • Department of Health Science
      Yamaguti, Yamaguchi, Japan
  • 2005
    • Hirosaki Gakuin University
      Aomori, Aomori, Japan
  • 1998–2002
    • University of Florida
      • Center for Exercise Science
      Gainesville, Florida, United States