Oxidative stress (OS) induced by acute exercise is reduced by chronic exercise. Ozone (O3) exposure produces OS. The aim of this study was to determine if aerobic exercise (AE) reduced OS produced by O3. A pilot experiment was performed with male Wistar rats submitted to AE (trained to swim 90 min/day). Adaptation to exercise was demonstrated three weeks after training by means of changes in reduced nitrates (NOx) in plasma. Therefore, two-week training was chosen for the following experiments. Six of twelve trained rats were exposed to O3 (0.5 ppm, 4 h/day, one hour before exercise). Two groups of sedentary animals (n = 6 each) were used as controls, one of which was exposed to O3. At the end of the experiments NOx, 8-isoprostane (8-IP), malondialdehyde (MDA), superoxide dismutase (SOD) activity, and carbonyls (CBs) were measured in plasma. CBs did not change in any group. O3-induced OS was manifested by reduced NOx and SOD activity, as well as increased 8-IP and MDA. Exercise significantly blocked O3 effects although SOD was also decreased by exercise (a greater drop occurring in the O3 group). It is concluded that AE protects against OS produced by O3 and the effect is independent of SOD.
Oxidative stress that is mediated through NADPH oxidase activity plays a role in the pathology of hypertension, and aerobic exercise training reduces NADPH oxidase activity. The involvement of genetic variation in the p22phox (CYBA) subunit genes in individual oxidative stress responses to aerobic exercise training has yet to be examined in Pre and Stage 1 hypertensives.
Ninety-four sedentary Pre and Stage 1 hypertensive adults underwent 6 months of aerobic exercise training at a level of 70% V̇O2max to determine whether the CYBA polymorphisms, C242T and A640G, were associated with changes in urinary 8-iso-prostaglandin F2α (8-iso-PGF2α), urinary nitric oxide metabolites (NOx), and plasma total antioxidant capacity (TAC).
Demographic and subject characteristics were similar among genotype groups for both polymorphisms. At baseline, a significant (P = 0.03) difference among the C2424T genotype groups in 8-iso-PGF2α levels was detected, with the TT homozygotes having the lowest levels and the CC homozygotes having the highest levels. However, no differences were found at baseline between the A640G genotype groups. After 6 months of aerobic exercise training, there was a significant increase in V̇O2max (P < 0.0001) in the entire study population. In addition, there were significant increases in both urinary 8-iso-PGF2α (P = 0.002) and plasma TAC (P = 0.03) levels and a significant decrease in endogenous urinary NOx (P < 0.0001). Overall, aerobic exercise training elicited no significant differences among genotype groups in either CYBA variant for any of the oxidative stress variables.
We found that compared with CYBA polymorphisms C242T and A640G, it was aerobic exercise training that had the greatest influence on the selected biomarkers; furthermore, our results suggest that the C242T CYBA variant influences baseline levels of urinary 8-iso-PGF2α but not the aerobic exercise-induced responses.
OXIDATIVE STRESS; AEROBIC EXERCISE; CYBA GENE; NITRIC OXIDE; ISOPROSTANES
We have recently demonstrated that oral intake of glycine propionyl-L-carnitine (GPLC) increases plasma nitrate/nitrite (NOx), a surrogate measure of nitric oxide production. However, these findings were observed at rest, and in previously sedentary subjects.
In the present study, we sought to determine the impact of oral GPLC on plasma NOx at rest and in response to a period of reactive hyperemia in resistance trained men.
Using a double blind, crossover design, 15 healthy men (24 ± 4 years) were assigned to GPLC (3 g/d PLC + 1044 mg glycine) and a placebo in random order, for a four-week period, with a two-week washout between condition assignment. Blood samples were taken from subjects at rest and at 0, 3, and 10 minutes following an ischemia-reperfusion protocol (six minutes of upper arm cuff occlusion at 200 mmHg followed by rapid reperfusion with cuff removal). Blood samples were taken from a forearm vein from the same arm used for the protocol and analyzed for total nitrate/nitrite. Data are presented as mean ± SEM.
A condition main effect (p = 0.0008) was noted for NOx, with higher values in subjects when using GPLC (45.6 ± 2.8 μmol·L-1) compared to placebo (34.9 ± 1.2 μmol·L-1). No time main effect was noted (p = 0.7099), although values increased approximately 12% from rest (37.7 ± 2.7 μmol·L-1) to a peak at 10 minutes post protocol (42.3 ± 3.3 μmol·L-1). The interaction effect was not significant (p = 0.8809), although paired time contrasts revealed higher values for GPLC compared to placebo at 3 (48.2 ± 6.7 vs. 34.9 ± 2.4 μmol·L-1; p = 0.033) and 10 (48.8 ± 5.9 vs. 35.7 ± 2.1 μmol·L-1; p = 0.036) minutes post protocol, with non-statistically significant differences noted at rest (41.8 ± 4.5 vs. 33.6 ± 2.5 μmol·L-1; p = 0.189) and at 0 minutes (43.6 ± 5.1 vs. 35.4 ± 2.7 μmol·L-1; p = 0.187) post protocol. An analysis by subject (collapsed across time) indicated that 11 of the 15 subjects experienced an increase in NOx with GPLC treatment.
These findings indicate that short-term oral GPLC supplementation can increase NOx in resistance trained men. However, as with many dietary supplements, there exist both "responders" and "non-responders" to treatment. Future work may focus on the mechanisms for the discrepancy in response to GPLC supplementation for purposes of NOx elevation.
Animal studies have shown that nitric oxide is involved in delayed ischemic preconditioning.
To determine whether plasma nitrates and nitrites (NOx−, as measure of nitric oxide) are modified by two consecutive effort tests and whether these changes translate into clinical improvement
Twenty-two patients with ischemic heart disease each performed two effort tests at 24-h intervals. Plasma NOx− level was determined and compared before and after both stress tests. Peak effort, double product at peak effort and maximal ST segment depression were considered clinical endpoints and were compared between the two tests.
Plasma NOx−increased slightly after the first exercise test compared with pretest value (17.05±1.6 μmol/mL versus 15.38±1.4 μmol/mL). In turn, after the second test there was a significant rise in NOx− level (23.65±2.2 μmol/mL versus 15.10±1.3 μmol/mL, P<0.03). The pretest values were almost identical between the two tests. Peak effort and double product at peak effort remained unchanged between the two tests. Although ischemic stress was the same, ST depression was significantly lower (P<0.01) for the second test (0.85±0.06 mm versus 1.73±0.16 mm).
Our study shows an increased plasma NOx−level after the second of two consecutive exercise stress tests at 24-h intervals, along with a decrease of electrocardiographic consequences of approximately the same ischemic stress. These findings are consistent with experimental data in animals, which point to nitric oxide as a trigger and effector of ischemic preconditioning.
Delayed preconditioning; Exercise; Nitrate; Nitric oxide; Nitrite
Exercise and physical activity have proven benefits for physical and psychological well-being. However, it is not clear if healthy young adults can enhance mood in everyday life through regular exercise. Earlier studies mainly showed positive effects of acute exercise and exercise programs on psychological well-being in children, older people and in clinical populations. Few studies controlled participants' physical activity in daily life, performed besides the exercise program, which can impact results. In addition the transition from mood enhancement induced by acute exercise to medium or long-term effects due to regular exercise is not yet determined. The purpose of this pilot study was to examine the acute effects of an aerobic running training on mood and trends in medium term changes of mood in everyday life of young adults. We conducted a 10-week aerobic endurance training with frequent mood assessments and continuous activity monitoring. 23 apprentices, separated into experimental and control group, were monitored over 12 weeks. To control the effectiveness of the aerobic exercise program, participants completed a progressive treadmill test pre and post the intervention period. The three basic mood dimensions energetic arousal, valence and calmness were assessed via electronic diaries. Participants had to rate their mood state frequently on 3 days a week at five times of measurement within 12 weeks. Participants' physical activity was assessed with accelerometers. All mood dimensions increased immediately after acute endurance exercise but results were not significant. The highest acute mood change could be observed in valence (p = 0.07; η2 = 0.27). However, no medium term effects in mood states could be observed after a few weeks of endurance training. Future studies should focus on the interaction between acute and medium term effects of exercise training on mood. The decreasing compliance over the course of the study requires the development of strategies to maintain compliance over longer periods.
mood; activity intensity; ambulatory assessment; aerobic exercise; randomized controlled trial; inactive people
Telomeres are potential markers of mitotic cellular age and are associated with physical ageing process. Long-term endurance training and higher aerobic exercise capacity (VO2max) are associated with improved survival, and dynamic effects of exercise are evident with ageing. However, the association of telomere length with exercise training and VO2max has so far been inconsistent. Our aim was to assess whether muscle telomere length is associated with endurance exercise training and VO2max in younger and older people.
Twenty men; 10 young (22–27 years) and 10 old (66–77 years), were studied in this cross-sectional study. Five out of 10 young adults and 5 out of 10 older were endurance athletes, while other halves were exercising at a medium level of activity. Mean telomere length was measured as telomere/single copy gene-ratio (T/S-ratio) using quantitative real time polymerase chain reaction. VO2max was measured directly running on a treadmill.
Older endurance trained athletes had longer telomere length compared with older people with medium activity levels (T/S ratio 1.12±0.1 vs. 0.92±0.2, p = 0.04). Telomere length of young endurance trained athletes was not different than young non-athletes (1.47±0.2 vs. 1.33±0.1, p = 0.12). Overall, there was a positive association between T/S ratio and VO2max (r = 0.70, p = 0.001). Among endurance trained athletes, we found a strong correlation between VO2max and T/S ratio (r = 0.78, p = 0.02). However, corresponding association among non-athlete participants was relatively weak (r = 0.58, p = 0.09).
Our data suggest that VO2max is positively associated with telomere length, and we found that long-term endurance exercise training may provide a protective effect on muscle telomere length in older people.
We previously reported an attenuation of both exercise hyperemia and measures of aerobic capacity in hypercholesterolemic mice. In this study we expanded upon the previous findings by examining the temporal and quantitative relationship of hypercholesterolemia to aerobic and anaerobic capacity and by exploring several potential mechanisms of dysfunction.
Eight-week old wild type (n=123) and apoE knockout (n=79) C57BL/6J mice were divided into groups with distinct cholesterol levels by feeding regular or high fat diets. At various ages the mice underwent treadmill ergospirometry. To explore mechanisms, aortic ring vasodilator function and nitrate (NOx) activity, urinary excretion of NOx, running muscle microvascular density and citrate synthase activity, as well as myocardial mass and histologic evidence of ischemia were measured.
At 8 weeks of age, all mice had similar measures of exercise capacity. All indices of aerobic exercise capacity progressively declined at 12 and 20 weeks of age in the hypercholesterolemic mice as cholesterol levels increased while indices of anaerobic capacity remained unaffected. Across the 4 cholesterol groups, the degree of aerobic dysfunction was related to serum cholesterol levels; a relationship that was maintained after correcting for confounding factors. Associated with the deterioration in exercise capacity was a decline in measures of nitric oxide-mediated vascular function while there was no evidence of aberrations in functional or oxidative capacities or in other components of transport capacity.
Aerobic exercise dysfunction is observed in murine models of genetic and diet-induced hypercholesterolemia and is associated with a reduction in vascular nitric oxide production.
Endothelial function; nitric oxide; oxygen consumption; cholesterol
Obesity has been associated with a variety of disease such as type II diabetes mellitus, arterial hypertension and atherosclerosis. Evidences have shown that exercise training promotes beneficial effects on these disorders, but the underlying mechanisms are not fully understood. The aim of this study was to investigate whether physical preconditioning prevents the deleterious effect of high caloric diet in vascular reactivity of rat aortic and mesenteric rings.
Male Wistar rats were divided into sedentary (SD); trained (TR); sedentary diet (SDD) and trained diet (TRD) groups. Run training (RT) was performed in sessions of 60 min, 5 days/week for 12 weeks (70–80% VO2max). Triglycerides, glucose, insulin and nitrite/nitrate concentrations (NOx-) were measured. Concentration-response curves to acetylcholine (ACh) and sodium nitroprusside (SNP) were obtained. Expression of Cu/Zn superoxide dismutase (SOD-1) was assessed by Western blotting.
High caloric diet increased triglycerides concentration (SDD: 216 ± 25 mg/dl) and exercise training restored to the baseline value (TRD: 89 ± 9 mg/dl). Physical preconditioning significantly reduced insulin levels in both groups (TR: 0.54 ± 0.1 and TRD: 1.24 ± 0.3 ng/ml) as compared to sedentary animals (SD: 0.87 ± 0.1 and SDD: 2.57 ± 0.3 ng/ml). On the other hand, glucose concentration was slightly increased by high caloric diet, and RT did not modify this parameter (SD: 126 ± 6; TR: 140 ± 8; SDD: 156 ± 8 and TRD 153 ± 9 mg/dl). Neither high caloric diet nor RT modified NOx- levels (SD: 27 ± 4; TR: 28 ± 6; SDD: 27 ± 3 and TRD: 30 ± 2 μM). Functional assays showed that high caloric diet impaired the relaxing response to ACh in mesenteric (about 13%), but not in aortic rings. RT improved the relaxing responses to ACh either in aortic (28%, for TR and 16%, to TRD groups) or mesenteric rings (10%, for TR and 17%, to TRD groups) that was accompanied by up-regulation of SOD-1 expression and reduction in triglycerides levels.
The improvement in endothelial function by physical preconditioning in mesenteric and aortic arteries from high caloric fed-rats was directly related to an increase in NO bioavailability to the smooth muscle mostly due to SOD-1 up regulation.
Little information is available on the effect of strength training on vascular function, particularly in older people.
To determine the effect of resistance training on arterial stiffness and endothelial function in older adults.
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).
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) μmol/l). There was no change in plasma concentration of endothelin‐1.
The results suggest that short term resistance training may increase NO production without stiffening central arteries in healthy older men.
strength training; arterial stiffness; endothelial function; nitric oxide
Objective: To investigate the effects of short term atorvastatin treatment on forearm vasodilatory response to reactive hyperaemia (RH%) and on components of the thrombosis–fibrinolysis system (antithrombin III, proteins and S, factors V and VII, von Willebrand factor, tissue plasminogen activator (tPA), and plasminogen activator inhibitor (PAI-1)) in patients with heart failure.
Patients and methods: 35 patients with heart failure were enrolled in this study; 17 patients received atorvastatin 10 mg/day and 18 patients received no statin for four weeks. Forearm blood flow (FBF) was measured by venous occlusion strain gauge plethysmography. RH% and forearm vasodilatory response to nitrate were defined as the percentage change of FBF from rest to the maximum flow during reactive hyperaemia and after nitrate administration, respectively. Plasma concentrations of antithrombin III, protein C, protein S, factor V, factor VII, von Willebrand factor, tPA, and PAI-1 were determined before and after treatment.
Results: Maximum hyperaemic FBF remained unchanged in both groups. Baseline FBF was slightly but not significantly decreased in the atorvastatin treated group. RH% was significantly increased only in the atorvastatin treated group, from mean (SD) 42.44 (18.9)% to 83.7 (36.1)% (p < 0.01). Plasma concentrations of antithrombin III (from mean (SD) 81.7 (11.37)% to 73.5 (13.8)%), protein C (from mean (SD) 88.3 (26.9)% to 63.9 (25.0)%), factor V (from mean (SD) 126.2 (33.4)% to 94.9 (29.8)%), tPA (from median (25th–75th percentile) 11.68 (8.60–20.95) ng/ml to 10.30 (8.65–15.12) ng/ml), and PAI-1 (from median (25th–75th percentile) 3.10 (2.15–4.40) IU/l to 1.90 (0.75–3.0) IU/l) were significantly decreased in the atorvastatin treated group (p < 0.05) but not in the control group. Plasma concentrations of von Willebrand factor, factor VII, and protein S remained unaffected in both groups.
Conclusion: Atorvastatin did not change the maximum hyperaemic flow, although it decreased plasma concentrations of antithrombin III, protein C, factor V, tPA, and PAI-1 in patients with heart failure. Therefore, short term treatment with atorvastatin may affect the expression of both endothelium and liver derived components of the thrombosis–fibrinolysis system in patients with heart failure.
heart failure; statins; endothelium; thrombosis; fibrinolysis
Nitric oxide (NO) may play important roles in rheumatoid arthritis (RA). RA is an inflammatory disease involving joints and other systems including salivary glands. To assess NO production in RA patients, we compared levels of serum, urine, and salivary nitrite and nitrate (NOx) in patients with RA and normal subjects, and we examined the relationships of these measures to disease activity. Serum, urine, and NOx levels as well as renal creatinine, NOx clearance and fractional excretion rates were compared in 25 RA patients and 20 age- and gender-matched healthy controls. Subjects were hospitalized for 3 days and placed on a NOxrestricted diet. NOx was assayed using nitrate reductase and the Griess reagent. RA activity was assessed using standard clinical and laboratory measures. While consuming a restricted diet for 3 days to eliminate the effects of oral intake of NOx, 24 hour urinary NOx excretion decreased in both RA patients and healthy controls. Urine NOx levels at all time points were not significantly different between RA patients and normal subjects. Serum NOx levels also decreased during the 3 days of NOx restriction, but RA patients had higher serum NOx levels at all time points compared with the control group. Likewise, serum NOx/creatinine ratios were higher in RA patients than in controls. Although basal salivary flow rate and tear flow were lower in RA patients, salivary NOx levels did not differ between normal and RA subjects. While renal creatinine clearance was not different between the two groups, we found that RA patients had lower renal NOx clearance and lower renal NOx fractional excretion. After correction of p values for multiple comparisons, there were no significant relationships for the RA group between measures of disease activity and the urinary NOx, serum NOx, or urinary NOx clearance. Despite interest in the use of NO as a marker of disease activity, alterations in renal NOx clearance and fractional excretion in RA make it difficult to assess in vivo NO production even with strict dietary restriction of NOx intake.
We investigated the effects of purified eicosapentaenoic acid (EPA) on vascular endothelial function and free fatty acid composition in Japanese hyperlipidemic subjects. In subjects with hyperlipidemia (total cholesterol ≥220 mg/dL and/or triglycerides ≥150 mg/dL), lipid profile and forearm blood flow (FBF) during reactive hyperemia were determined before and 3 months after supplementation with 1800 mg/day EPA. Peak FBF during reactive hyperemia was lower in the hyperlipidemic group than the normolipidemic group. EPA supplementation did not change serum levels of total, HDL, or LDL cholesterol, apolipoproteins, remnant-like particle (RLP) cholesterol, RLP triglycerides, or malondialdehyde-modified LDL cholesterol. EPA supplementation did not change total free fatty acid levels in serum, but changed the fatty acid composition, with increased EPA and decreased linoleic acid, γ-linolenic acid, and dihomo-γ-linolenic acid. EPA supplementation recovered peak FBF after 3 months. Peak FBF recovery was correlated positively with EPA and EPA/arachidonic acid levels and correlated inversely with dihomo-γ-linolenic acid. EPA supplementation restores endothelium-dependent vasodilatation in hyperlipidemic patients despite having no effect on serum cholesterol and triglyceride patterns. These results suggest that EPA supplementation may improve vascular function at least partly via changes in fatty acid composition.
Exercise may contribute to the maintenance of vascular function via enhanced liberation and action of bone-marrow-derived progenitor cells. Activity related changes in oxidative stress may also influence the number and function of these cells. In the present study, we sought to determine (i) whether adaptations in reactive hyperaemic FBF (forearm blood flow) response associated with long-term endurance exercise and short-term detraining were related to resting putative progenitor cell number and function, and (ii) whether oxidative stress affected these factors. Participants included men with a history of more than 30 years of moderate-to-high-intensity exercise (HI group) and healthy low-active age- and BMI (body mass index)-matched control subjects (LO group). Vascular reactive hyperaemic FBF response, resting CD34+ and CD34+/VEGFR2+ (vascular endothelial growth factor receptor 2+] cell number, CFU-EC (colony-forming unit-endothelial cell) count and CFU-EC senescence were evaluated. Oxidative stress measures included OxLDL (oxidized low-density lipoprotein) and TAC (total antioxidant capacity). These measures were assessed following 10 days of detraining in the HI group. The HI group had greater peak reactive hyperaemic FBF responses compared with the LO group, despite no difference in resting CD34+ cell number, CD34+/VEGFR2+ cell number, CFU-EC colonies or CFU-EC senescence. With detraining in the HI group, CD34+ cells declined 44 %, and the percentage change in CD34+/VEGFR2+ cells was positively correlated with the change in FBF response to reactive hyperaemia. The percentage change in CD34+/VEGFR2+ cells and the percentage change in EPC (endothelial progenitor cell) senescence with detraining were related to the percentage change in TAC. These results reveal that changes in reactive hyperaemic FBF are closely related to activity dependent dynamic changes in CD34+/VEGFR2+ cell number, which may be influenced by alterations in oxidative stress.
aging; antioxidant; endothelial progenitor cell; exercise; forearm blood flow; physical inactivity
The weakening of the cardiovascular system associated with aging could be countered by increasing levels of physical activity and functional fitness. However, inconsistent findings have been found, and the variety of characteristics of exercise used in previous studies may partly explain that inconsistent results.
To investigate the training effect of sixteen weeks of moderate intensity, progressive aerobic and strength-based training on metabolic health of older women and men.
Sixty three sedentary individuals (mean (SD) age 76 (8) years) were randomly assigned to control (n = 31) or exercising (n = 32) groups. The training group was separated to aerobic (n = 18) or strength-based (n = 14). Training took place three times a week. Subjects agreed not to change their diet or lifestyle over the experimental period.
Exercising group attained after treatment significant differences on body weight, waist circumference, body mass index, diastolic blood pressure, triglycerides, total cholesterol, HDL-cholesterol, LDL-cholesterol, total cholesterol/HDL-cholesterol relationship, high sensitivity C-reactive protein, and 6-minute walk distance. The control group only had significant differences on waist circumference.
The training programs produced significant benefits on metabolic health indicators of sedentary older women and men.
There is a well-established relationship between increased arterial stiffness and cardiovascular mortality. We examined whether a long-term aerobic exercise intervention (6 months) would increase arterial compliance in older adults with hypertension complicated by Type 2 diabetes (T2DM) and hyperlipidemia. A total of 52 older adults (mean age 69.3±0.6 years, 30 males and 22 females) with diet/oral hypoglycemic-controlled T2DM, hypertension and hypercholesterolemia were recruited. Subjects were randomly assigned to one of two groups: an aerobic group (6 months vigorous aerobic exercise, AT group) and a non-aerobic group (6 months of no aerobic exercise, NA group). Arterial stiffness was measured as pulse-wave velocity (PWV) using the Complior device. Aerobic training decreased arterial stiffness as measured by both radial (P=0.001, 2-way analysis of variance with repeated measures) and femoral (P=0.002) PWV. This was due to a decrease in arterial stiffness in the AT group after 3 months of training, which was not maintained after 6-month training for either radial (P=0.707) or femoral (P=0.680) PWV. Our findings indicate that in older adults with multiple cardiovascular risk factors, short-term improvements in arterial stiffness became attenuated over the long term.
gerontology; aerobic exercise; arterial stiffness; Type 2 diabetes
Both nitric oxide and asymmetrical dimethylarginine (ADMA) play a critical role in the regulation of cerebral blood flow, though their neuroprotective and cytotoxic effects are still under investigation. In this study we found that nitrate/nitrite (NOx) levels in plasma, ischemic brain tissue, and cerebrospinal fluid (CSF) increased significantly 24h after 2h transient middle cerebral artery occlusion (MCAO) in rats. ADMA levels were unchanged in plasma, but decreased significantly in CSF 24h following MCAO. The CSF ADMA/NOx ratio decreased markedly following ischemia. Rats protected by expression of the chaperonin GroEL or its folding deficient mutant D87K had lower plasma NOx levels at 24h reperfusion. ADMA, NO, and their ratio in CSF merit further study as biomarkers for ischemic brain injury.
NO; ADMA; CSF; focal ischemia; rat; GroEL
Insulin binding to monocytes was examined in trained athletes (long distance runners) and in sedentary control subjects in the resting state and after 3 h of exercise at 40% of maximal aerobic power. At rest, specific binding of 125-I-insulin to monocytes was 69% higher in athletes than in sedentary controls and correlated with maximal aerobic power. The increase in insulin binding was primarily due to an increase in binding capacity. During acute exercise, insulin binding fell by 31% in athletes but rose by 35% in controls. The athletes had a smaller decline in plasma glucose and a lower respiratory exchange ratio during exercise than did controls. We conclude that physical training increases insulin binding to monocytes in the resting state but results in a fall in insulin binding during acute exercise. Changes in insulin binding in athletes thus may account for augmented insulin sensitivity at rest as well as a greater shift from carbohydrate to fat usage during exercise than is observed in untrained controls.
To describe the contribution of changes in fitness and fatness resulting from exercise training on changes in submaximal exercise blood pressure (BP) during treadmill testing.
Design and Setting
Prospective, randomized, controlled trial
Sedentary older adults (n=115), with untreated prehypertension or mild hypertension
Six-month supervised aerobic and strength training
Main Outcome Measurement
BP was assessed at rest and during each stage of a maximal graded exercise test (GXT) that determined VO2peak. General and regional fatness was assessed by anthropometry, dual-energy x-ray absorptiometry, and magnetic resonance imaging. BP changes were calculated for each GXT stage and multivariate regression models were used to describe the association of changes in exercise BP with changes in fitness and fatness.
After training, exercisers versus controls had significantly increased VO2peak and significantly lower measures of general and regional fatness. Also, stage-specific SBP was significantly lower at stage 3 (−9.4 vs. −1.6 mmHg, p=0.03) and stage 4 (−7.9 vs. −1.2 mmHg, p=0.03). Pooled regression analysis across all stages showed that exercisers had a 7.1 mmHg reduction in SBP, but this reduction fell short of statistical significance (p=0.12) compared to controls. A 1.0 ml/kg/min increase in VO2peak and a 1.0 cm decrease in waist circumference independently predicted a 1.0 mmHg decrease in exercise SBP (p=0.04 and p=0.001, respectively).
Decreased exercise SBP was independently associated with decreased waist circumference, a marker of abdominal obesity, and increased fitness. Our findings suggest that exercise training improves multiple factors that have independent influence on SBP.
hypertension; exercise test; randomized controlled trial; obesity; physical fitness
We investigated to see whether an altered role of nitric oxide (NO) system is involved in erythropoietin (EPO)-induced hypertension in chronic renal failure (CRF). Male Sprague-Dawley rats were five-sixths nephrectomized to induce CRF. Six weeks after the operation, EPO or vehicle was injected for another 6 weeks. Plasma and urine nitrite/nitrate (NOx) levels were determined. Expression of NO synthase (NOS) proteins in the aortae and kidneys were also determined. In addition, the isometric tension of isolated aorta in response to acetylcholine and nitroprusside was examined. Blood pressure progressively rose in CRF groups, the degree of which was augmented by EPO treatment. Plasma NOx levels did not differ among the groups, while urine NOx levels were lower in CRF groups. Endothelial NOS expression was lower in the kidney and aorta in CRF rats, which was not further affected by EPO-treatment. The inducible NOS expression in the kidney and aorta was not different among the groups. Acetylcholine and sodium nitroprusside caused dose-dependent relaxations of aortic rings, the degree of which was not altered by EPO-treatment. Taken together, EPO-treatment aggravates hypertension in CRF, but altered role of NO system may not be involved.
The generation of reactive oxygen species (ROS) plays a major role in endothelial signaling and function. Of the several potential sources of ROS in the vasculature, the endothelial NADPH Oxidase (Nox) family of proteins, Nox1, Nox2, Nox4 and Nox5, are major contributors of ROS. Excess generation of ROS contributes to the development and progression of vascular disease. While hyperoxia stimulates ROS production through Nox proteins, hypoxia appears to involve mitochondrial electron transport in the generation of superoxide. ROS generated from Nox proteins and mitochondria are important for oxygen sensing mechanisms. Physiological concentrations of ROS function as signaling molecule in the endothelium; however, excess ROS production leads to pathological disorders like inflammation, atherosclerosis, and lung injury. Regulation of Nox proteins is unclear; however, antioxidants, MAP Kinases, STATs, and Nrf2 regulate Nox under normal physiological and pathological conditions. Studies related to redox regulation of Nox should provide a better understanding of ROS and its role in the pathophysiology of vascular diseases.
NADPH Oxidase; ROS; Endothelium; Redox; Nox proteins
Physical activity has been shown to enhance endothelial function of central and peripheral vascular beds. The primary purpose of the present study was to test the hypothesis that a short-term exercise training program would result in enhanced endothelium-dependent vasorelaxation of a major artery supplying blood flow to the knee joint, the middle genicular artery. Female Yucatan miniature swine were randomly assigned into exercise trained (n = 7) or sedentary (n = 7) groups. Exercise trained pigs underwent a daily exercise training program on treadmills for 7 days. In vitro assessment of vasorelaxation was determined in a dose response manner by administrating increasing doses of 3 different dilators; adenosine diphosphate, bradykinin, and sodium nitroprusside. The role of nitric oxide synthase and cyclooxygenase pathways in vasomotor responses was evaluated with specific inhibitors using nitro-L-arginine methyl ester and indomethacin incubation, respectively. The results of this investigation indicate that adenosine and bradykinin-induced endothelium-dependent vasorelaxation were significantly enhanced in middle genicular artery from exercise trained pigs (p < 0.05). Endothelium-independent vasorelaxation was not altered with exercise training as determined by the response to sodium nitroprusside. The findings of the present investigation indicate that short-term exercise training enhances endothelial function of middle genicular artery through adaptations in the nitric oxide synthase and by non-nitric oxide synthase, non-cyclooxygenase pathways.
physical activity; vasorelaxation; knee vasculature
We determined the relationship between abdominal circumference and the concentration of nitric oxide (NO), an endothelial cell product known to play an important role in the regulation of vascular tone and thrombocyte activations.
Subjects were 177 men and 339 women aged 40 or over who were free from a history of diabetes or malignancy. Analysis of covariance was applied to examine the gender-specific and smoking-status-specific associations of abdominal fat volume measured as waist circumference, waist-hip ratio, and waist-to-stature ratio, with serum NO level represented by the concentration of NO metabolites (NOx; nitrate plus nitrite).
Although men showed no statistical association between abdominal fat accumulation and NOx concentration, abdominal adiposity seemed to inversely affect the serum NOx concentration of never- and current-smoking women.
Our results suggest that a reduction in NO bioactivity occurs with abdominal fat accumulation in women. The underlying biological mechanism might involve adipocytokines secreted from visceral fat, but is yet to be elucidated.
metabolic syndrome; nitric oxide; adipocytokine; endothelial dysfunction; analysis of covariance
Results of previous studies have shown that exercise training can improve cognitive functions in healthy older people. Some studies have demonstrated that long-term combination exercise training can facilitate memory function improvement better than either aerobic or strength exercise training alone. Nevertheless, it remains unclear whether short-term combination exercise training can improve diverse cognitive functions in healthy older people or not. We investigate the effects of four weeks of short-term combination exercise training on various cognitive functions (executive functions, episodic memory, short-term memory, working memory, attention, reading ability, and processing speed) of healthy older people.
A single-blinded intervention with two parallel groups (combination exercise training; waiting list control) is used. Testers are blind to the study hypothesis and the participants’ group membership. Through an advertisement in a local newspaper, 64 healthy older adults are recruited and then assigned randomly to a combination exercise training group or a waiting list control group. Participants in the combination exercise training group must participate in the short-term combination exercise training (aerobic and strength exercise training) three days per week during the four weeks (12 workouts in total). The waiting list group does not participate in the combination exercise training. The primary outcome measure is the Stroop test score: a measure of executive function. Secondary outcome measures are assessments including the Verbal Fluency Task, Logical Memory, First and Second Names, Digit Span Forward, Digit span backward, Japanese Reading Test, Digit Cancellation Task, Digit Symbol Coding, and Symbol Search. We assess these outcome measures before and after the intervention.
This report is the first of a study that investigates the beneficial effects of short-term combination exercise training on diverse cognitive functions of older people. Our study is expected to provide sufficient evidence of short-term combination exercise’s effectiveness.
This trial was registered in The University Hospital Medical Information Network Clinical Trials Registry (Number UMIN000007828).
Both increased and decreased nitric oxide (NO) synthesis have been reported in patients treated with interferon-α (IFN-α). Animal studies showed that IFN-α administration results in increased levels of biogenic amines, subsequent activation of monoamine oxidases (MAOs), and finally in a change in NO production due to the H2O2 generated by MAOs. We examined the potential relationship between NO production in plasma and MAO-B activity in platelets of 43 cancer patients during 8 weeks of treatment with IFN-α. NO synthesis was quantitated by measuring both the ratio of citrulline and arginine (CIT/ARG-ratio) and total nitrite/nitrate (NOx) levels. Compared to baseline, MAO activity and NOx increased, while the CIT/ARG-ratio decreased. No associations were found between NOx, MAO and CIT/ARG-ratio. Only few associations were observed between changes in the biochemical parameters and changes in psychopathology induced by IFN-α, of which the association between changes in CIT and lassitude was the most consistent. The results suggest that peripheral NO production and MAO activity are unrelated to each other, and that peripheral changes in these biochemical parameters induced by IFN-α are unlikely to contribute to definite psychiatric disturbance.
Citrulline; Depression; Interferon-α; Nitric oxide; Monoamine oxidase; Cancer
Skeletal muscle blood flow is coupled with the oxygenation state of hemoglobin in young adults, whereby the erythrocyte functions as an oxygen sensor and releases ATP during deoxygenation to evoke vasodilation. Whether this function is impaired in humans of advanced age is unknown.
To test the hypothesis that older adults demonstrate impaired muscle blood flow and lower intravascular ATP during conditions of erythrocyte deoxygenation.
Methods and Results
We show impaired forearm blood flow (FBF) responses during two conditions of erythrocyte deoxygenation (systemic hypoxia and graded handgrip exercise) with age, and this is due to reduced local vasodilation. In young adults, both hypoxia and exercise significantly increased venous [ATP] and ATP effluent (FBF × [ATP]) draining skeletal muscle. In contrast, hypoxia and exercise did not increase [ATP]v in older adults, and both [ATP]v and ATP effluent were substantially reduced compared with young despite similar levels of deoxygenation. Next, we demonstrate that this cannot be explained by augmented extracellular ATP hydrolysis in whole blood with age. Finally, we found that deoxygenation-mediated ATP release from isolated erythrocytes is essentially non-existent in older adults.
Skeletal muscle blood flow during conditions of erythrocyte deoxygenation is markedly reduced in aging humans, and reductions in plasma ATP and erythrocyte-mediated ATP release may be a novel mechanism underlying impaired vasodilation and oxygen delivery during hypoxemia with advancing age. Because aging is associated with elevated risk of ischemic cardiovascular disease and exercise intolerance, interventions targeting erythrocyte-mediated ATP release may offer therapeutic potential.
Aging; Blood Flow; ATP; Erythrocyte; Hypoxia