Effects of habitual aerobic exercise on the relationship between intramyocellular or extramyocellular lipid content and arterial stiffness.

The accumulation of intramyocellular lipid (IMCL) and extramyocellular lipid (EMCL) is associated with arterial stiffness in middle-aged and older adults. Habitual aerobic exercise induces the improvement of arterial stiffness with reduction in fat accumulation. However, the relationship between aerobic exercise-induced changes in muscular lipids and arterial stiffness remains unclear. The purpose of this study was to investigate whether habitual aerobic exercise-induced changes in IMCL and EMCL content would lead to an improvement of arterial stiffness. First, in a cross-sectional study, we investigated whether cardiorespiratory fitness level affects the association between IMCL or EMCL content and arterial stiffness in 60 middle-aged and older subjects (61.0±1.3 years). Second, in an intervention study, we examined whether aerobic exercise training-induced changes in IMCL and EMCL content are associated with a reduction in arterial stiffness in 18 middle-aged and older subjects (67.0±1.7 years). In the cross-sectional study, IMCL content was negatively correlated with brachial-ankle pulse wave velocity (baPWV) (r=-0.47, P<0.05), whereas EMCL content was positively correlated with baPWV (r=0.48, P<0.05) in the low-fitness group, but was not correlated in the high-fitness group. Furthermore, 8-week aerobic exercise training in older adults increased IMCL content and reduced EMCL content. The training-induced change in baPWV was negatively correlated with training-induced changes in IMCL but was positively correlated with training-induced changes in EMCL. These findings suggest that aerobic exercise training-induced changes in IMCL and EMCL content may be related to a reduction in arterial stiffness in middle-aged and older adults.

DHEA Administration Activates Transcription of Muscular Lipid Metabolic Enzymes via PPARα and PPARδ in Obese Rats.

Administration of dehydroepiandrosterone (DHEA), a precursor of sex steroid hormones, reduces total and visceral fat mass and elevates adipocytic adiponectin gene expression. The aim of this study is to investigate whether levels of peroxisome proliferator-activated receptors (PPARs) in muscle and transcription of PPAR target genes are affected by long-term DHEA administration or exercise training, and whether altered PPAR levels are associated with circulating adiponectin level in obese rats. After 14 weeks on a high-sucrose diet, obese male Wistar rats were assigned randomly to one of 3 groups: control, DHEA administration (1 mg/kg body weight), or exercise training (treadmill running for 1 h, 25 m/min, 5 days/week) for 6 weeks (n=7 for each group). Plasma DHEA and total adiponectin levels in the DHEA-treated and exercise-training groups were significantly higher than those in the obese control group. Additionally, DHEA administration and exercise training significantly increased muscular PPARα and PPARδ protein levels, with a concomitant increase in mRNA expression of 3ß-hydroxyacyl-CoA dehydrogenase and cytochrome c oxidase IV, which are target genes of PPARα and PPARδ respectively. Moreover, DHEA administration increased these protein and mRNA levels to the same degree as exercise training. Circulating adiponectin level was positively correlated with plasma DHEA and with muscle levels of PPARα and PPARδ. These results suggest that in obese rats, secretion of adiponectin due to chronic DHEA administration and exercise training may contribute to an increase in the transcription of genes encoding lipid metabolic enzymes, mediated via elevated expression of PPARα and PPARδ in muscle.

Elevated pentraxin 3 level at the early stage of exercise training is associated with reduction of arterial stiffness in middle-aged and older adults.

Regular exercise improves aging-induced deterioration of arterial stiffness, and is associated with elevated production of pentraxin 3 (PTX3) and anti-inflammatory as well as anti-atherosclerotic effects. However, the time-dependent effect of exercise training on arterial stiffness and PTX3 production remains unclear. The purpose of this study was to investigate the time course of the association between the effects of training on the circulating PTX3 level and arterial stiffness in middle-aged and older adults. Thirty-two healthy Japanese subjects (66.2±1.3 year) were randomly divided into two groups: training (exercise intervention) and sedentary controls. Subjects in the training group completed 8 weeks of aerobic exercise training (60-70% peak oxygen uptake (VO2peak) for 45 min, 3 days per week); during the training period, we evaluated plasma PTX3 concentration and carotid-femoral pulse wave velocity (cfPWV) every 2 wk. cfPWV gradually declined over the 8-week training period, and was significantly reduced after 6 and 8 week of exercise intervention (P<0.05). Plasma PTX3 level was significantly increased after 4 weeks of the intervention (P<0.05). In addition, the exercise training-induced reduction in cfPWV was negatively correlated with the percent change in plasma PTX3 level after 6 week (r=-0.54, P<0.05) and 8 weeks (r=-0.51, P<0.05) of the intervention, but not correlated at 4 weeks. Plasma PTX3 level was elevated at the early stage of the exercise training intervention, and was subsequently associated with training-induced alteration of arterial stiffness in middle-aged and older adults.

Dehydroepiandrosterone administration increased trabecular mass and dihydrotestosterone levels in the cancellous region of the tibia in young female rats.

The aim of the present study was to determine whether dehydroepiandrosterone (DHEA) administration affects bone mass and local sex hormone levels in the cancellous region of young female rats. Eleven female rats (6 weeks old) were randomly divided into 2 groups: control rats (CON, n=5) and rats treated with DHEA (DHEA, n=6). DHEA dissolved in sesame oil was administered to the DHEA group intraperitoneally at 20 mg DHEA/kg body weight, and the CON group was treated with vehicle only (sesame oil, 0.5 ml). The rats were treated with DHEA or vehicle for 3 consecutive days, followed by 1 day of no treatment. The experimental period was 8 weeks. According to dual-energy X-ray absorptiometry and high-resolution microcomputed tomography data, the DHEA group exhibited increased trabecular bone mineral density (BMD), bone volume, and tibial thickness compared to the findings in the CON group, whereas no effect was observed on cortical BMD or morphometry. The concentrations of free testosterone and estradiol in the cancellous region of the tibia did not differ between the 2 groups, but the DHT concentration was significantly higher in the DHEA group than in the CON group. These findings suggest that an increase in local DHT levels may stimulate an increase in trabecular bone mass during growth phases in female rats.

Acute administration of diosgenin or dioscorea improves hyperglycemia with increases muscular steroidogenesis in STZ-induced type 1 diabetic rats.

Acute dehydroepiandrosterone (DHEA) administration improves hyperglycemia in rats with streptozotocin (STZ)-induced type 1 diabetes mellitus. Diosgenin, a steroid structurally similar to DHEA (dehydroepiandrosterone), is contained highly levels in dioscorea; however, it is still unclear whether this natural product improves hyperglycemia in the type 1 diabetes model rats through an increase muscular GLUT4 signaling. After 1 week of STZ injection, fasting glucose level was measured in blood taken from the tail vein every 30 min for 150 min after injection of diosgenin or dioscorea (3mg/kg). On another day, muscle was resected 150 min after diosgenin or dioscorea injections. Serum DHEA level increased significantly 120 min after diosgenin or dioscorea injections; concomitantly, blood glucose level decreased significantly. Moreover, GLUT4 translocation, as well as phosphorylation of Akt and PKC ζ/λ, increased significantly by diosgenin or dioscorea administration. However, these effects of diosgenin and dioscorea were blocked by a 5α-reductase inhibitor that inhibits synthesizing dehydrotestosterone (DHT) from testosterone. Additionally, significant correlations were observed between blood glucose level, GLUT4 translocation level, and muscular sex steroid hormone level 150 min after the administrations. These results suggest that the diosgenin-induced increase in the DHEA level may contribute to the improvement of hyperglycemia by activating the muscular GLUT4 signaling pathway in type 1 diabetes model rats.

Adverse effects of coexistence of sarcopenia and metabolic syndrome in Japanese women.

BACKGROUND/OBJECTIVES: Little information is available regarding the interactions of sarcopenia and metabolic syndrome (MetS) in the risks of these age-associated diseases in women. The present cross-sectional study was performed to investigate whether the coexistence of sarcopenia and MetS further increases the risks of lifestyle-related diseases in Japanese women. SUBJECTS/METHODS: Healthy Japanese women (n=533) aged 30-84 participated in this study. MetS was defined as higher body mass index, fasting plasma glucose, systolic or diastolic blood pressure and blood lipid abnormalities. Appendicular muscle mass and bone mineral density (BMD) were measured using dual-energy X-ray absorptiometry. The criterion of low muscle mass and strength defined median skeletal muscle index (appendicular muscle mass/height², kg/m²) and handgrip strength. RESULTS: Two-way ANCOVA with adjustment for age, body fat percentage and whole-body lean tissue mass indicated that sarcopenia and MetS interacted to produce a significant effect on HbA1c, systolic blood pressure, triglycerides and brachial-ankle pulse wave velocity in Japanese women. The systolic blood pressure, triglycerides and brachial-ankle pulse wave velocity were significantly higher in women with coexisting sarcopenia and MetS than in healthy controls or in those with sarcopenia or MetS alone. The HbA1c in the coexisting sarcopenia and MetS group was higher than in healthy controls and sarcopenia subjects. CONCLUSIONS: The coexistence of sarcopenia and MetS further increases the risks of cardiovascular diseases, such as type 2 diabetes mellitus, hypertension, arterial stiffness and hyperlipidemia even adjustment of age and body composition in adult Japanese women.

Mitochondrial macrohaplogroup associated with muscle power in healthy adults.

The present study was undertaken to examine the effect of mitochondrial haplogroups on aerobic and anaerobic performance phenotypes such as maximum oxygen consumption, muscle power, and muscle mass. We recruited 474 healthy Japanese individuals and measured their physical performance phenotypes such as peak oxygen uptake, muscle power, and muscle mass. The genotypes for 186 polymorphisms in the mitochondrial DNA were determined, and the haplotypes were classified into 2 macrohaplogroups (i. e., N and M) and 12 haplogroups (i. e., F, B, A, N9a, N9b, M7a, M7b, G1, G2, D4a, D4b, and D5). When we compared the 2 major Japanese macrohaplogroups, leg extension power (P=0.0395), leg extension power based on body weight (P=0.0343), and vertical jump performance (P=0.0485) were significantly higher in subjects with mitochondrial macrohaplogroup N than in those with macrohaplogroup M. However, peak oxygen uptake was similar between the 2 groups. When we analyzed the 12 haplogroups, all of the measured parameters were similar among them. In conclusion, mitochondrial macrohaplogroup N may be one of the determinant factors of anaerobic physical performance phenotype such as muscle power.

ACTN3 polymorphism affects thigh muscle area.

Muscle mass is an important factor influencing the activity of daily living in older adults. We aimed to investigate whether alpha-actinin-3 (ACTN3) gene R577X polymorphism affects muscle mass in older Japanese women. A total of 109 women (mean+/-SD, 64.1+/-6.0 years) were genotyped for the R/X variant of ACTN3. Mid-thigh muscle cross-sectional area (CSA) was assessed using MRI and compared using analysis of covariance models adjusted for body weight. In addition, physical activity and protein intake were measured as the living environmental factors affecting muscle mass. The ACTN3 R577X genotype distributions of the subjects were 19, 63 and 27 for the RR, RX, and XX genotypes, respectively. No differences in physical activity and protein intake were observed among the genotypes. The XX genotype showed lower thigh muscle CSA compared with RR&RX genotype (mean+/-SEM; XX: 69.1+/-1.8 cm(2), RR&RX: 73.6+/-1.1 cm(2); p<0.05). The results of the present study suggest that ACTN3 R577X polymorphism influences muscle mass in older Japanese women.

DHEA improves impaired activation of Akt and PKC zeta/lambda-GLUT4 pathway in skeletal muscle and improves hyperglycaemia in streptozotocin-induced diabetes rats.

AIM: Addition of dehydroepiandrosterone (DHEA) to a cultured skeletal muscle locally synthesizes 5alpha-dihydrotestosterone (DHT). It induced activation of glucose metabolism-related signalling pathway via protein kinase B (Akt) and protein kinase C zeta/lambda (PKC zeta/lambda)-glucose transporter-4 (GLUT4) proteins. However, such an effect of DHEA in vivo remains unclear. METHODS: Using streptozotocin (STZ)-induced rats with type 1 diabetes mellitus, we tested the hypothesis that a single bout of DHEA injection in the rats improves hyperglycaemia and muscle GLUT4-regulated signalling pathway. After 1 week of STZ injection (55 mg kg(-1)) with male Wistar rats, fasting glucose concentrations were determined in a blood sample taken from the tail vein. Blood glucose levels were then monitored for 180 min after DHEA or sesame oil (control) was injected (n = 10 for each group). RESULTS: Blood glucose levels decreased significantly for 30-150 min after 2 mg DHEA injection in the STZ rats. In the skeletal muscle, expression and translocation of GLUT4 protein, phosphorylation of Akt and PKC zeta/lambda, and phosphofructokinase and hexokinase enzyme activities increased significantly by DHEA injection. However, DHEA-induced improvements in Akt and PKC zeta/lambda-GLUT4 pathways were blocked by a DHT inhibitor. CONCLUSION: These results suggest that a single bout of DHEA injection can improve hyperglycaemia and activate the glucose metabolism-related signalling pathway via Akt and PKC zeta/lambda-GLUT4 proteins of skeletal muscles in rats. Moreover, these results show that a DHEA-induced increase in muscle glucose uptake and utilization might contribute to improvement in hyperglycaemia in type 1 diabetes mellitus.

Voluntary running exercise attenuates the progression of endothelial dysfunction and arterial calcification in ovariectomized rats.

AIM: Loss of oestrogen synthesis capacity after menopause contributes to increases in arterial stiffness and calcification. Exercise training improves arterial stiffness and calcification. However, the mechanism of exercise training-induced improvement of arterial stiffness and calcification remains unclear. METHOD: We examined the mechanism by using aortas of sham-operated rats (sham control; SC), ovariectomized rats (OVX control; OC), OVX plus treatment with vitamin D(3) plus nicotine (VDN) rats (OV sedentary; OVSe), which is an animal model of endothelial dysfunction and arterial calcification, and voluntary running wheel exercise for 8 weeks plus OVX plus VDN rats (OV exercise; OVEx). RESULTS: The arterial tissue calcium and endothelin-1 (ET-1: a vasoconstrictor peptide and a potent regulator of arterial calcification) levels were significantly higher in OVSe rats compared with the SC and OC rats, whereas these levels in the OVEx rats were significantly lower than in the OVSe rats. Additionally, arterial expression of endothelial nitric oxide synthase (eNOS), which is an enzyme that produces nitric oxide (NO: a vasodilator substance), was reduced in OVSe rats. However, exercise training prevented the decrease in eNOS expression. Moreover, there was a significant positive correlation between arterial calcium level and arterial ET-1 level. CONCLUSION: These findings suggest that exercise training-induced improvement of ET-1 and NO prevents the impairment of endothelial function after menopause in females, and this improvement may result in less arterial calcification.

Contribution of systemic arterial compliance and systemic vascular resistance to effective arterial elastance changes during exercise in humans.

BACKGROUND: Effective arterial elastance (Ea), an index of arterial load, increases with elevations in left ventricular elastance to maximize the efficiency of left ventricular stroke work during exercise. Systemic arterial compliance (C) and vascular resistance (R) are the primary components contributing to Ea, and R plays a greater role in determining Ea at rest. We hypothesized that the contribution of C to Ea increases during exercise to maintain an optimal balance between arterial load and ventricular elastance, and that the increase in Ea is due primarily to a reduction in C. AIM: The aim of this study was to investigate the contributions of C and R to Ea during exercise. METHODS: Ea (0.9 x systolic blood pressure/stroke volume), C (stroke volume/pulse pressure), R (mean blood pressure/cardiac output), and cardiac cycle length (T) were measured at rest and during exercise of 40%, 60% and 80% maximal oxygen uptake (O(2max)) using Doppler echocardiography in 45 healthy men. RESULTS: Ea did not differ between rest and 40%O(2max), but it was greater at 60% and 80%O(2max). C markedly decreased during exercise in an exercise intensity-dependent manner. The changes in R/T during exercise were small, whereas it decreased at 40%O(2max) and gradually increased at 60% and 80%O(2max). CONCLUSIONS: The present results suggest that the contribution of systemic arterial compliance to effective arterial elastance increases during exercise. Therefore, we propose that the increase in arterial load during exercise is mainly driven by a reduction in systemic arterial compliance.

Effects of leg resistance training on arterial function in older men.

BACKGROUND: Little information is available on the effect of strength training on vascular function, particularly in older people. OBJECTIVE: To determine the effect of resistance training on arterial stiffness and endothelial function in older adults. METHOD: Eleven healthy men (mean (SEM) age 64 (1) years) performed 12 weeks of resistance training involving knee flexion and extension (three sets a day, two days a week). RESULTS: Resistance training increased maximal muscle power by 16% (p<0.0001). Arterial stiffness as assessed by aortic pulse wave velocity did not change with resistance training. Plasma concentration of nitric oxide (NO), measured as its stable end product (nitrite/nitrate), had increased (p<0.05) after resistance training (61.2 (10.4) v 39.6 (3.2) micromol/l). There was no change in plasma concentration of endothelin-1. CONCLUSION: The results suggest that short term resistance training may increase NO production without stiffening central arteries in healthy older men.

Gene expression profiling of exercise-induced cardiac hypertrophy in rats.

AIMS: Exercise training causes physiological cardiac hypertrophy, which acts to enhance cardiac function during exercise. However, the underlying molecular mechanisms are unclear. We investigated gene expression profile of exercise training-induced cardiac hypertrophy using left ventricle (LV) excised from exercise-trained and sedentary control rats (12-week old). METHOD: Rats in the training group exercised on a treadmill for 8-week. RESULTS: Left ventricular mass index and wall thickness in the exercise-trained group were significantly greater than that in the control group, indicating that the trained rats developed cardiac hypertrophy. Of the 3800 genes analysed in the microarray analyses, a total of 75 relevant genes (upregulation of 33 genes and downregulation of 42 genes) displayed alterations with exercise training. Among these genes, we focused on glycogen synthase kinase (GSK)-3beta, calcineurin-inhibitor (Cain), and endothelin (ET)-1 for their implicated roles in pathological cardiac hypertrophy, and confirmed the results of microarray analysis at mRNA and protein/peptide levels using quantitative PCR, Western blot, and EIA analyses. The gene expression of GSK-3beta decreased significantly and those of Cain and ET-1 increased significantly with exercise training. Furthermore, LV mass index was significantly correlated with GSK-3beta protein activity (r = -0.70, P < 0.01) and tissue ET-1 concentration (r = 0.52, P < 0.05). There were no changes in gene expressions in brain natriuretic peptide (BNP), angiotensin-correcting enzyme (ACE), interleukin-6, and vascular cell adhesion molecule (VCAM)-1. CONCLUSION: These findings suggest that physiological and pathological LV hypertrophy may share some of the same molecular mechanisms in inducing LV hypertrophy (e.g. GSK-3beta, Cain, and ET-1) and that other genes (e.g. BNP, ACE) may differentiate physiological from pathological LV hypertrophy.

Acute exercise causes an enhancement of tissue renin-angiotensin system in the kidney in rats.

AIMS: Initially, the renin-angiotensin system (RAS) produced through the classical endocrine pathway was well known for its regulation of blood pressure. However, it was revealed that a local autocrine and/or paracrine RAS may exist in a number of tissues (such as kidney). Exercise causes a redistribution of tissue blood flow, by which the blood flow is greatly increased in active muscles, whereas it is decreased in the splanchnic circulation (such as in the kidney). We hypothesized that exercise causes an enhancement of tissue RAS in the kidney. METHODS: We studied whether exercise affects expression of angiotensinogen and angiotensin-converting enzyme (ACE) and tissue angiotensin II level in the kidney. The rats performed treadmill running for 30-min. Immediately after this exercise, kidney was quickly removed. Control rats remained at rest during this 30-min period. RESULTS: The expression of angiotensinogen mRNA in the kidney was markedly higher in the exercise rats than in the control rats. ACE mRNA in the kidney was significantly higher in the exercise rats than in the control rats. Western blot analysis confirmed significant upregulation of ACE protein in the kidney after exercise. Tissue angiotensin II level was also increased by exercise. CONCLUSION: The present study suggests that the exercise-induced enhancement of tissue RAS in the kidney causes vasoconstriction and hence decreases blood flow in the kidney, which are helpful in increasing blood flow in active muscles, thereby contributing to the redistribution of blood flow during exercise.

Non-invasive assessment of cardiac output during exercise in healthy young humans: comparison between Modelflow method and Doppler echocardiography method.

AIMS: The Modelflow method can estimate cardiac output from arterial blood pressure waveforms using a three-element model of aortic input impedance (aortic characteristic impedance, arterial compliance, and systemic vascular resistance). We tested the reliability of a non-invasive cardiac output estimation during submaximal exercise using the Modelflow method from finger arterial pressure waveforms collected by Portapres in healthy young humans. METHODS: The Doppler echocardiography method was used as a reference method. Sixteen healthy young subjects (nine males and seven females) performed a multi-stage cycle ergometer exercise at an intensity corresponding to 70, 90, 110 and 130% of their individual ventilatory threshold for 2 min each. The simultaneous estimation of cardiac output (15 s averaged data) using the Modelflow and Doppler echocardiography methods was performed at rest and during exercise. RESULTS AND CONCLUSION: The Modelflow-estimated cardiac output correlated significantly with the simultaneous estimates by the Doppler method in all subjects (r = 0.87, P < 0.0001) and the SE of estimation was 1.93 L min-1. Correlation coefficients in each subject ranged from 0.91 to 0.98. Although the Modelflow method overestimated cardiac output, the errors between two estimates were not significantly different among the exercise levels. These results suggest that the Modelflow method using Portapres could provide a reliable estimation of the relative change in cardiac output non-invasively and continuously during submaximal exercise in healthy young humans, at least in terms of the relative changes in cardiac output.

Exercise training improves ageing-induced decrease in eNOS expression of the aorta.

AIMS: Ageing impairs endothelial function such as the regulation of vascular tone. The release of nitric oxide (NO), which has a potent vasodilator effect and antiatherosclerotic property, is decreased in the aorta of aged rats. Exercise training, however, has been reported to increase the expression of endothelial NO synthase (eNOS) in the aorta of young rats. In aged rats, it is not known whether the expression of eNOS is altered by exercise training. We hypothesized that exercise training would improve the ageing-induced decrease in eNOS expression in vessels, and examined the messenger RNA (mRNA) and protein expression of eNOS in the aorta of sedentary-young rats (sedentary-young group; 4 months old), sedentary-aged rats (sedentary-aged group; 23 months old), and swim-trained aged rats (training-aged group; 23 months old, swimming training for 8 weeks, 5 days week(-1), 90 min day(-1)). RESULTS: Body weight was significantly lower, and citrate synthase activity in the epitrochlearis muscle was significantly higher in the training-aged group compared with the sedentary-aged group. The mRNA expression of eNOS in the aorta was significantly higher in the training-aged group than in the sedentary-aged group, while it was significantly lower in both the sedentary-aged and training-aged groups than in the sedentary-young group. The expression of eNOS protein in the aorta was also significantly higher in the training-aged group than in the sedentary-aged group, while it was also significantly lower in the sedentary-aged group, but not in the training-aged group, than in the sedentary-young group. CONCLUSION: The present results revealed that the production of eNOS in the aorta decreases with ageing, and that the decreased production is increased by exercise training in aged rats, which may produce beneficial effects on the impaired cardiovascular system caused by ageing.

Physiological and pathological cardiac hypertrophy induce different molecular phenotypes in the rat.

Pressure overload, such as hypertension, to the heart causes pathological cardiac hypertrophy, whereas chronic exercise causes physiological cardiac hypertrophy, which is defined as athletic heart. There are differences in cardiac properties between these two types of hypertrophy. We investigated whether mRNA expression of various cardiovascular regulating factors differs in rat hearts that are physiologically and pathologically hypertrophied, because we hypothesized that these two types of cardiac hypertrophy induce different molecular phenotypes. We used the spontaneously hypertensive rat (SHR group; 19 wk old) as a model of pathological hypertrophy and swim-trained rats (trained group; 19 wk old, swim training for 15 wk) as a model of physiological hypertrophy. We also used sedentary Wistar-Kyoto rats as the control group (19 wk old). Left ventricular mass index for body weight was significantly higher in SHR and trained groups than in the control group. Expression of brain natriuretic peptide, angiotensin-converting enzyme, and endothelin-1 mRNA in the heart was significantly higher in the SHR group than in control and trained groups. Expression of adrenomedullin mRNA in the heart was significantly lower in the trained group than in control and SHR groups. Expression of beta(1)-adrenergic receptor mRNA in the heart was significantly higher in SHR and trained groups than in the control group. Expression of beta(1)-adrenergic receptor kinase mRNA, which inhibits beta(1)-adrenergic receptor activity, in the heart was markedly higher in the SHR group than in control and trained groups. We demonstrated for the first time that the manner of mRNA expression of various cardiovascular regulating factors in the heart differs between physiological and pathological cardiac hypertrophy.

Effects of exercise training of 8 weeks and detraining on plasma levels of endothelium-derived factors, endothelin-1 and nitric oxide, in healthy young humans.

Vascular endothelial cells produce nitric oxide (NO), which is a potent vasodilator substance and has been proposed as having antiatherosclerotic property. Vascular endothelial cells also produce endothelin-1 (ET-1), which is a potent vasoconstrictor peptide and has potent proliferating activity on vascular smooth muscle cells. Therefore, ET-1 has been implicated in the progression of atheromatous vascular disease. Because exercise training has been reported to produce an alteration in the function of vascular endothelial cells in animals, we hypothesized that exercise training influences the production of NO and ET-1 in humans. The purpose of the present study was to examine whether chronic exercise could influence the plasma levels of NO (measured as the stable end product of NO, i.e., nitrite/nitrate [NOx]) and ET-1 in humans. Eight healthy young subjects (20.3 +/- 0.5 yr old) participated in the study and exercised by cycling on a leg ergometer (70% VO2max for 1 hour, 3-4 days/week) for 8 weeks. Venous plasma concentrations of NOx and ET-1 were measured before and after (immediately before the end of 8-week exercise training) the exercise training, and also after the 4th and 8th week after the cessation of training. The VO2max significantly increased after exercise training. After the exercise training, the plasma concentration of NOx significantly increased (30.69 +/- 3.20 vs. 48.64 +/- 8.16 micromol/L, p < 0.05), and the plasma concentration of ET-1 significantly decreased (1.65 +/- 0.14 vs. 1.23 +/- 0.12 pg/mL, p < 0.05). The increase in NOx level and the decrease in ET-1 level lasted to the 4th week after the cessation of exercise training and these levels (levels of NOx and ET-1) returned to the basal levels (the levels before the exercise training) in the 8th week after the cessation of exercise training. There was a significant negative correlation between plasma NOx concentration and plasma ET-1 concentration. The present study suggests that chronic exercise causes an increase in production of NO and a decrease in production of ET-1 in humans, which may produce beneficial effects (i.e., vasodilative and antiatherosclerotic) on the cardiovascular system.

Whole-body energy mapping under physical exercise using positron emission tomography.

We attempted to visualize dynamic adjustment of glucose utilization in humans in the whole-body organs during physical exercise by using three-dimensional positron emission tomography (3D-PET) and [18F]-2-fluoro-deoxy-glucose (FDG). Twelve healthy male volunteers collaborated on the study; six subjects were assigned to the resting control group (C) and the other six to the running group (E). Group E subjects performed running on a flat road for 35 min. After 15 min of running, subjects injected FDG and kept on running thereafter for another 20 min. Group C subjects sat on a comfortable chair in a quiet room for 35 min after the injection of FDG. After scanning by PET, the regions of interest (ROIs) were manually set on brain, heart, thorax, abdomen, lower extremities, and the rest of the body on the corresponding transaxial images. The uptake of FDG in each region was evaluated as the % fraction of FDG accumulation relative to the total amount of whole-body accumulation. The results revealed increase of FDG uptake after running in the lower leg muscles from 24.6 +/- 9.5% to 43.1 +/- 4.7% and in the heart from 2.3 +/- 0.4% to 2.8 +/- 0.6%. The differences were significant (P < 0.05). These increases reflect the rise in energy consumption in leg and heart muscles and were balanced by the reduction of energy consumption in the other part of the body. FDG uptake in the abdominal region reduced from 37.3 +/- 7.2% to 19.7 +/- 4.9%. However, FDG uptake in the brain remained stable, i.e., 11.9 +/- 2.8% at rest and 10.3 +/- 2.5% after exercise. Thus, 3D-PET is a tool to visualize the dynamic adjustment of energy consumption during physical exercise in humans.

Intense exercise causes decrease in expression of both endothelial NO synthase and tissue NOx level in hearts.

Cardiac myocytes produce nitric oxide (NO). We studied the effects of intense exercise on the expression of NO synthase (NOS) and the tissue level of nitrite (NO(2)(-))/nitrate (NO(3)(-)) (i.e., NOx), which are stable end products of NO in the heart. Rats ran on a treadmill for 45 min. Immediately after this exercise, the heart was quickly removed. Control rats remained at rest during the same 45-min period. The mRNA level of endothelial NOS (eNOS) in the heart was markedly lower in the exercised rats than in the control rats. Western blot analysis confirmed downregulation of eNOS protein in the heart after exercise. Tissue NOx level in the heart was significantly lower in the exercised rats than in the control rats. The present study revealed for the first time that production of NO in the heart is decreased by intense exercise. Because NO attenuates positive inotropic and chronotropic responses to beta(1)-adrenergic stimulation in the heart, the decrease in cardiac production of NO by intense exercise may contribute to the acceleration of increase in myocardial contractility and heart rate during intense exercise.