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Biomedical subjects

Shinya Kuno

Publications and source records attributed to Shinya Kuno.

14 recordsLinked to original sources

Polymorphism in endothelin-related genes limits exercise-induced decreases in arterial stiffness in older subjects.

Increase in arterial stiffness is associated with aging, which is improved by regular exercise. Endothelin (ET) system has crucial roles in regulating vascular tone and in the progression of atherosclerosis. We hypothesized that molecular variations (ie, gene polymorphisms) in ET-related gene might affect exercise-induced improvement in arterial stiffness with age in human subjects. The present study provides a cross-sectional investigation of 191 healthy middle-aged and older (65+/-1 years) human subjects to clarify the relationship between the regular exercise-induced improvement of arterial stiffness and the gene polymorphisms of ET converting enzyme (ECE)-1, ECE-2, ET-A receptor (ET-A), and ET-B receptor (ET-B). The study subjects were divided into active and inactive groups based on the median value (186 kcal/d) of energy expenditure. Brachial-ankle arterial pulse wave velocity (baPWV) was used to evaluate arterial stiffness. All individuals were genotyped for 4 different polymorphisms of the ET system: 2013(+289)A/G in intron 17 of ECE-1, 669(+17)T/C in intron 5 of ECE-2, 958A/G in exon 6 of ET-A, and 831A/G in exon 4 of ET-B. The baseline baPWV was significantly lower in the active group without any change in blood pressure. Polymorphisms in ECE-1 influenced basal blood pressure. Polymorphisms in ECE-1 and ECE-2 had no effect on baPWV between active and inactive groups. However, polymorphisms in both ET-A and ET-B affected baPWV in the 2 groups. The present results suggest that differences in ET-A and ET-B polymorphisms may influence the response of the vascular wall to exercise whereas ECE-1 polymorphisms may affect basal blood pressure.

Aged↗

Age-related reduction of systemic arterial compliance induces excessive myocardial oxygen consumption during sub-maximal exercise.

Reduction of systemic arterial compliance (SAC) with aging increases left ventricular afterload. The present study was designed to examine whether age-related reduction of SAC is related to excessive myocardial oxygen consumption during sub-maximal aerobic exercise. We studied elderly (60-69 years; n = 25) and senior (70-82 years; n = 25) subjects. We measured SAC immediately before the start of the ramp-fashion exercise (i.e., at the end of the 20 W warm-up exercise) and the double product (DP: systolic blood pressure x heart rate) during the ramp-fashion exercise (20-50 W). SAC was significantly lower in senior subjects (0.76 +/- 0.25 ml mmHg(-1) m(-2)) compared with elderly subjects (0.95 +/- 0.22 ml mmHg(-1) m(-2)). DP was higher in senior subjects (20 W: 14.3 +/- 3.1; 30 W: 15.9 +/- 4.2; 40 W: 17.7 +/- 4.9; 50 W: 20.6 +/- 5.6 [x 10(3) mmHg bpm]) than in elderly subjects (12.8 +/- 3.0, 14.0 +/- 3.5, 15.1 +/- 4.0, 17.1 +/- 4.3 [x 10(3) mmHg bpm]). In total subjects, SAC correlated significantly with DP (r = -0.64, r = -0.64, r = -0.64, r = -0.64). In senior subjects, SAC was related significantly to DP (r = -0.83, r = -0.78, r = -0.76, r = -0.74). In elderly subjects, SAC tended to correlate with DP although its relationships were not statistically significant (r = -0.34, r = -0.36, r = -0.33, r = -0.31). Correlation coefficients at each respective exercise intensity were significantly higher in senior subjects compared with elderly subjects. These results suggest that the age-related reduction of SAC is related to excessive myocardial oxygen consumption during sub-maximal aerobic exercise in older humans, but this relation does not become significant until the SAC reduction becomes pronounced.

Age Factors↗

Effects of short-term endurance training on aortic distensibility in young males.

BACKGROUND: Short-term endurance exercise training can increase aortic distensibility. The effect of exercise on arterial distensibility, however, may not last long term. PURPOSE: We evaluated the effects of short-term exercise training and detraining on aortic distensibility in 10 sedentary young males (21.0 +/- 0.6 yr, mean +/- SE; range 19-24 yr). METHODS: The subjects underwent 8 wk of endurance training on a cycle ergometer at 70% of maximal oxygen consumption (VO(2max)), for 60 min at a time and on alternate days (3-4 d.wk(-1). The detraining period consisted of a return to sedentary days for 8 wk. The aortic pulse wave velocity (APWV) was measured before and immediately after training and during the detraining period. RESULTS: The VO(2max) was significantly increased after training (pre: 2240.0 +/- 71.4 mL, after: 2728.8 +/- 82.5 mL, mean +/- SE, P < 0.0001) and remained at increased levels during the detraining period (after 4 wk: 2671.2 +/- 73.6 mL, P < 0.001; after 8 wk: 2628.0 +/- 85.0 mL, P < 0.001). The APWV was significantly decreased after training (pre: 5.80 +/- 0.15 m.s(-1), after: 5.50 +/- 0.21 m.s(-1), P < 0.01) but returned close to the baseline after detraining for 4 wk (5.66 +/- 0.13 m.s, P < 0.18). CONCLUSION: Our data suggest that short-term exercise training can improve aortic distensibility, but the effect cannot be maintained without continuing physical exercise.

Adult↗

Aortic stiffness and aerobic exercise: mechanistic insight from microarray analyses.

INTRODUCTION/PURPOSE: Regular aerobic exercise reduces aortic stiffness. However, the mechanisms by which chronic exercise lowers arterial stiffness are not known. To determine the molecular mechanisms of these changes, the alteration of gene expression in the aorta by aerobic exercise training was measured with the microarray technique. METHODS/RESULTS: The differences in expression levels of 3800 genes in the abdominal aorta of sedentary control rats (8 wk old) and exercise-trained rats (8 wk old, treadmill running for 4 wk) were compared by the microarray analysis. Aortic pulse wave velocity (PWV) was lower and systemic arterial compliance was higher (both P < 0.05) in the exercise-trained group than in the control group. Of the 323 genes that displayed differential expression (upregulation of 206 genes and downregulation of 117 genes), a total of 29 genes (24 upregulated and 5 downregulated genes) were identified as potential candidate genes that may be involved in vasodilation and arterial destiffening. Using real-time quantitative polymerase chain reaction, we confirmed the results of microarray analysis that prostaglandin EP2 receptor (PGE-EP2R), prostaglandin EP4 receptor (PGE-EP4R), C-type natriuretic peptide (CNP), and endothelial nitric oxide synthase (eNOS) genes were differentially expressed. Furthermore, there were modest correlations between arterial stiffness and levels of these factors. Differential expression of eNOS gene was further verified at protein level by using Western blot analysis. CONCLUSION: These results suggest that exercise training induces the altered expression in several genes including prostaglandin, CNP, and nitric oxide in the aorta and that these molecular changes (particularly eNOS as its protein expression was altered) may contribute, at least in part, to the beneficial effect of exercise training on aortic stiffness.

Animals↗

Effect of arterial lumen enlargement on carotid arterial compliance in normotensive postmenopausal women.

A reduction in central arterial compliance has been identified as an independent risk factor for future cardiovascular disease. The aim of the present study was to determine the influence of age-related carotid arterial enlargement on carotid arterial compliance in postmenopausal females, using a cross-sectional study design. Carotid arterial properties were measured with applanation tonometry and ultrasound system in 113 normotensive females (aged 50-78). Brachial-ankle pulse wave velocity (baPWV) measured by a plethysmographic technique was used as an index of arterial stiffness. In comparisons among the three age groups (50-59, 60-69, and 70-78 years old), baPWV (F=11.9, p<0.001) and carotid systolic (F=4.5, p<0.05) and pulse pressures (F=9.6, p<0.0001), and lumen diameter (F=5.6, p<0.01) increased with advancing age. Carotid arterial compliance gradually decreased with age, but not significantly. A stepwise regression analysis revealed that carotid systolic pressure and lumen diameter and age were independent correlates of carotid arterial compliance. After carotid lumen diameter was taken into account (ANCOVA), the differences in carotid arterial compliance among the three age groups became significant (F=3.8, p<0.05). These results suggest that an increase in arterial lumen diameter might compensate for the age-related increase in arterial stiffness and limit the deterioration of the buffering capacity of the central artery in normotensive postmenopausal females.

Adaptation, Physiological↗

Mechanical power during maximal treadmill walking and running in young and elderly men.

This study determined mechanical power during movements specific to maximal walking and running using a non-motorized treadmill in 38 elderly [69.4 (5.0) years] and 50 young [24.3 (3.4) years] men. The mean mechanical power over a period of time covering six steps, during which the belt velocity peaked and then kept almost plateau, was determined as a performance score in each of maximal walking (WP) and running (RP). In terms of the value relative to body mass, the relative difference between the two age groups was greater for RP (61.7%) than for WP (21.4%) or isometric knee extension (34.1%) and flexion torque (43.8%). In the two groups, WP was significantly ( P<0.05) correlated to knee extension (r=0.582 for the elderly and r=0.392 for the young) and flexion torque (r=0.524 for the elderly and r=0.574 for the young). Similarly, RP was also significantly (P<0.05) correlated to knee extension (r=0.627 for the elderly and r=0.478 for the young) and flexion torque (r=0.500 for the elderly and r=0.281 for the young). In these relationships, the WP adjusted statistically by thigh muscle torque was similar in the two age groups. However, the corresponding value for RP was significantly higher in the young than in the elderly. The findings here indicate that: (1) the difference between the young and elderly men in mechanical power is greater during maximal running than maximal walking, and (2) although the thigh muscle torque contributes to the power production during the two maximal exercise modes in the two age groups, the RP is greater in the young than in the elderly regardless of the difference in the thigh muscle torque.

Adult↗

Influences of age and sex on abdominal muscle and subcutaneous fat thickness.

This study aimed to investigate the influences of age and sex on the thickness of the rectus abdominis muscle and subcutaneous fat at the abdomen. The two tissue thickness values were determined using ultrasonography in a total of 194 young (20-29 years) and elderly (70-79 years) persons of both genders. In both sexes, the elderly groups showed significantly thinner muscle and thicker fat than the younger groups. The percentage of the mean value of subcutaneous fat thickness in the elderly group compared to that in the younger group was higher in the women (176%) than in the men (128%), but the corresponding value of muscle thickness was similar between men (68%) and women (65%). In both generations, the women had significantly thinner muscle and thicker fat than the men. The percentage of the mean value of subcutaneous fat thickness in the women compared to that in the men was higher in the elderly group (169%) than in the younger group (123%), but the corresponding value of muscle thickness was similar between the younger (80%) and elderly (77%) groups. In every group, subcutaneous fat thickness significantly correlated with waist circumference, but muscle thickness did not. The findings here indicated that: (1). aging was associated with a decrease of muscle thickness and an increase of subcutaneous fat at the abdomen in men and women, with a similar relative loss of muscle thickness in both genders and a greater increase of subcutaneous fat thickness in women than in men, and (2). subcutaneous fat rather than muscle thickness reflected waist circumference, regardless of age and gender.

Abdominal Muscles↗

Moderate regular exercise increases basal production of nitric oxide in elderly women.

Vascular endothelial cells produce nitric oxide (NO), which is a potent vasodilator substance and is thought to have antiatherosclerotic properties. Therefore, it has also been proposed that NO may be useful to regulate vascular tonus and prevent progression of atherosclerosis. On the other hand, NO activity reduces with aging. We previously reported that the plasma nitrite/nitrate (NOx: the stable end product of NO) concentration was significantly increased by intense aerobic exercise training in healthy young humans. We hypothesized that lifestyle modification (e.g., even mild regular exercise training) can increase NO production in previously sedentary older humans. We measured the plasma NOx concentration before and after a mild aerobic exercise training regimen (cycling on a leg ergometer at 80% ventilatory threshold for 30 min, 5 days/week) for 3 months in elderly women. In addition, we assessed the plasma concentration of cyclic guanosine monophosphate (cGMP), a second messenger of NO, in the same samples. The individual ventilatory threshold increased significantly after the 3-month exercise training. The blood pressure at rest significantly decreased after exercise training. These results suggest that the 3-month exercise training in the older women produced favorable physiological effects. The plasma concentration of NOx significantly increased by the exercise training, and the plasma concentration of cGMP also increased by the exercise training. The present study suggests that even a mild regular aerobic-endurance exercise increases NO production in previously sedentary older humans, which may have beneficial effects (i.e., antihypertensive and antiatherosclerotic effects by endogenous NO) on the cardiovascular system.

Aged↗

Growth trend of the quadriceps femoris muscle in junior Olympic weight lifters: an 18-month follow-up survey.

Isometric torque and the cross-sectional area (CSA) of the quadriceps femoris muscle (QF) were measured twice at an interval of 18 months in seven junior Olympic weight lifters (aged 15.5-17.1 years at the start of the study) to investigate the growth trend of this muscle group in junior athletes specializing in strength and power events. The CSAs of the QF and its four constituent muscles were determined at 30% (proximal to the knee), 50%, and 70% of femur length (Fl) using a magnetic resonance imaging method. Only at 30%Fl were significant increases found in the CSAs of the QF and all constituent muscles, except for the rectus femoris. At this level, the CSA of the vastus medialis relative to the QF decreased significantly, suggesting a predominant hypertrophy in the vastus intermedius and vastus lateralis muscles. Isometric torque during knee extension increased significantly compared, to the CSA for the QF measured at the three levels. Thus, the present results indicate that, at least at high school age, the QF for junior Olympic weight lifters is characterized by a preferential hypertrophy at the level proximal to the knee joint, with an increase in knee extension torque relative to the CSA.

Adaptation, Physiological↗

Aerobic exercise training reduces plasma endothelin-1 concentration in older women.

Endothelial function deteriorates with aging. On the other hand, exercise training improves the function of vascular endothelial cells. Endothelin-1 (ET-1), which is produced by vascular endothelial cells, has potent constrictor and proliferative activity in vascular smooth muscle cells and, therefore, has been implicated in regulation of vascular tonus and progression of atherosclerosis. We previously reported significantly higher plasma ET-1 concentration in middle-aged than in young humans, and recently we showed that plasma ET-1 concentration was significantly decreased by aerobic exercise training in healthy young humans. We hypothesized that plasma ET-1 concentration increases with age, even in healthy adults, and that lifestyle modification (i.e., exercise) can reduce plasma ET-1 concentration in previously sedentary older adults. We measured plasma ET-1 concentration in healthy young women (21-28 yr old), healthy middle-aged women (31-47 yr old), and healthy older women (61-69 yr old). The plasma level of ET-1 significantly increased with aging (1.02 +/- 0.08, 1.33 +/- 0.11, and 2.90 +/- 0.20 pg/ml in young, middle-aged, and older women, respectively). Thus plasma ET-1 concentration was markedly higher in healthy older women than in healthy young or middle-aged women (by approximately 3- and 2-fold, respectively). In healthy older women, we also measured plasma ET-1 concentration after 3 mo of aerobic exercise (cycling on a leg ergometer at 80% of ventilatory threshold for 30 min, 5 days/wk). Regular exercise significantly decreased plasma ET-1 concentration in the healthy older women (2.22 +/- 0.16 pg/ml, P < 0.01) and also significantly reduced their blood pressure. The present study suggests that regular aerobic-endurance exercise reduces plasma ET-1 concentration in older humans, and this reduction in plasma ET-1 concentration may have beneficial effects on the cardiovascular system (i.e., prevention of progression of hypertension and/or atherosclerosis by endogenous ET-1).

Adult↗

Antioxidant capacity in rat skeletal muscle tissues determined by electron spin resonance.

The amount of radical scavenging activity in muscle is unknown. The present study examines whether electron spin resonance (ESR) could measure and distinguish antioxidant capacity in muscle with different contractile and metabolic characteristics. Specimens of the soleus, plantaris, gastrocnemius (deep/surface portions), heart and diaphragm were obtained from female Wistar rats (n=7; 12 weeks old). Scavenging activity against superoxide anions in these specimens were determined by ESR using a spin-trapping chemical (5,5-dimethyl-1-pyrroline-N-oxide). The ESR signal intensity of reaction mixtures containing muscle tissues was significantly lower in the heart, soleus, diaphragm and deep portion of the gastrocnemius than in the plataris and surface portion of the gastrocnemius. Thus, the amount of scavenging activity converted into superoxide dismutase activity was the highest in the heart, and higher in the soleus, diaphragm and deep portion of the gastrocnemius than in other muscles (ANOVA, P<0.01). In addition, scavenging activity significantly correlated with citrate synthase activity (r=0.72, P<0.01, n=42) and myoglobin content (r=0.63, P<0.01, n=42). These findings suggested that ESR and spin-trapping can be detect differences in free radical scavenging activity among muscle tissues with different metabolic characteristics.

Animals↗

The effects of low-intensity single-leg exercise on regional arterial stiffness.

We examined the effect of low-intensity single-leg exercise (20 or 30 watt, 5 min) on pulse wave velocity from the femoral to the ankle arteries in 18 young men. After the exercise, the velocity significantly decreased in the exercised leg, but not in the counterpart, suggesting that the decrease in arterial stiffness in the exercised leg was induced mainly by exercise-related regional factors.

Adult↗

Validity of ultrasonograph muscle thickness measurements for estimating muscle volume of knee extensors in humans.

This study aimed to investigate the suitability of using ultrasonograph muscle thickness (MT) measurements to estimate the muscle volume (MV) of the quadriceps femoris as an alternative approach to magnetic resonance imaging (MRI). The subjects were 46 men aged from 20 to 70 years who were randomly allocated to either a validation or a cross-validation group. In the validation group, multiple and simple regression equations, which used a set of MT values determined at mid-thigh and thigh length (1) and the product of pi, (MT/2)2, and l [pi x (MT/2)2 x l], respectively, as independent variables, were derived to estimate the MV measured by MRI. Because the two equations were cross-validated, the data from the two groups were pooled to generate the final prediction equations: MV (cm3)=(MT x 311.732)+(l x 53.346) -2058.529 as the multiple regression equation and MV (cm3) = [pi x (MT/ 2)2 x l] x 1.1176+663.040 as the simple regression equation. In the multiple regression equation, MT explained 75% of the variation in the MV measured by MRI. The r2 and the standard error of the estimate (SEE) of the equations were 0.824 and 175.6 cm3 (10.6%), respectively, for the multiple regression equation and 0.829 and 173.7 cm3 (10.5%), respectively, for the simple regression equation. Thus, the present results indicate that ultrasonograph MT measurements at mid-thigh are useful for estimating the MV of knee extensors. However, the observed SEE values suggest that the prediction equation obtained in this study may be limited to population studies rather than individual assessments in longitudinal studies.

Adult↗

Polymorphisms in control region of mtDNA relates to individual differences in endurance capacity or trainability.

The purpose of this study was to investigate whether the polymorphisms in the control region of mitochondrial DNA (mtDNA) related to individual difference in the endurance capacity or trainability. Fifty-five sedentary males participated in this study and were submitted to an 8-week endurance training program. The VO(2 max) was determined before and after training. Total DNA was extracted from the blood, and the sequence of the mtDNA control region was determined. The polymorphism in the mtDNA control region was decided based on the "Cambridge sequence." In 29 of the 55 subjects, vastus lateralis muscle biopsy samples were taken at rest before and after the training program. MtDNA content and CS (citrate synthase) activity in skeletal muscle was measured as the phenotype of the polymorphisms in the mtDNA control region. The VO(2 max) increased to 48.2 +/- 6.3 ml/min/kg from 42.1 +/- 6.0 as a result of the 8-week training (p < 0.05). The numbers of polymorphisms in determined 1,122 bp were 11.1 +/- 2.9 variable sites per person, and the total numbers of polymorphisms were 125 variable sites. The subjects were classified into two groups at each variable site, the Cambridge sequence (Cam) group and the non-Cambridge sequence (non-Cam) group. There were significant differences in pre-VO(2 max) between the two groups at each mtDNA nucleotide positions 16298, 16325, and 199, and in % Delta VO(2 max) at 16223 and 16362. Twenty-nine subjects who underwent the biopsy revealed significant differences in pre-CS activity at 194 and pre-mtDNA content at 514. Also, significant differences were found in the change rate of VO(2 max )and CS activity as a result of training between the two groups at 16519. In conclusion, it suggested that mtDNA polymorphisms in the control region might result in individual differences in endurance capacity or trainability.

Adult↗