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1.  Reduction of Arterial Stiffness by Exercise Training Is Associated with Increasing Plasma Apelin Level in Middle-Aged and Older Adults 
PLoS ONE  2014;9(4):e93545.
Aging-induced deterioration of arterial stiffness is decreased by regular exercise, and increased nitric oxide (NO) production participates in this effect. Apelin regulates endothelial NO synthase in endothelial cells, promoting NO production. However, the effect of aerobic exercise training on circulating apelin levels in healthy middle-aged and older adults remains unknown. Accordingly, this study aimed to clarify the effects of regular aerobic exercise on apelin concentrations in middle-aged and older adults. Thirty-four healthy middle-aged and older subjects (67.0 ± 1.3 years) were randomly divided into two groups: exercise intervention and sedentary controls. Subjects in the training group completed 8-week of aerobic exercise training (60–70% peak oxygen uptake [VO2peak] for 45 min, 3 days/week). Before and after the intervention, we evaluated plasma apelin and nitrite/nitrate (NOx) concentrations, VO2peak, and arterial stiffness index. In the training group, VO2peak was significantly increased, and carotid β-stiffness was significantly decreased, after the intervention (P<0.05). Moreover, plasma apelin and NOx levels were significantly increased in the training group after the intervention (P<0.05). Additionally, there was a correlation between the training effects of plasma apelin levels and carotidβ-stiffness (r = −0.508, P = 0.032) and plasma NOx levels (r = 0.494, P = 0.037). By contrast, none of these parameters changed significantly in the control group. These results suggest that the increased in plasma apelin levels may be associated with exercise training-induced alternation of arterial stiffness in middle-aged and older adults.
doi:10.1371/journal.pone.0093545
PMCID: PMC3972107  PMID: 24691252
2.  Association of serum NOx level with clustering of metabolic syndrome components in middle-aged and elderly general populations in Japan 
Objectives
The aim of this study was to determine whether the serum nitrite plus nitrate (NOx) level correlates with biomarkers that are known components of the metabolic syndrome (MetS).
Methods
Serum NOx levels were measured using a commercial kit in 608 Japanese men and women between the ages of 39 and 85 years. Multivariate adjustments for age, smoking status, alcohol consumption and exercise were made in the analysis of covariance (ANCOVA). The components of the metabolic syndrome were defined based on the following criteria: body mass index (BMI) ≥25.0 kg/m2, glycated hemoglobin (HbA1c) ≥5.6%, systolic blood pressure ≥130 mmHg or diastolic blood pressure ≥85 mmHg, high-density lipoprotein-cholesterol (HDL-C) ≤1.03 mmol/l for men and ≤1.29 mmol/l for women and triglyceride ≥1.69 mmol/l.
Results
The logarithmically transformed age-adjusted serum NOx (lnNOx) value was significantly higher in the low HDL-C group (1.76 ± 0.05 μmol/l; p < 0.05) than MetS component groups (1.65 ± 0.01 μmol/l) in men, but no difference was found in women. The means of serum lnNOx after multivariate adjustment were 1.64, 1.65, 1.64, 1.66, and 1.81 μmol/l for 0, 1, 2, 3, and 4–5 MetS components for all subjects, respectively. The results of ANCOVA confirmed that the serum lnNOx level was significantly correlated with the clustering of MetS components in both men and women (p < 0.0001 for trend).
Conclusion
Our results suggest that an increase in the clustering of MetS components was associated with the increase in serum NO levels in our general population.
doi:10.1007/s12199-007-0001-1
PMCID: PMC2698239  PMID: 19568878
Analysis of covariance; Cyclic guanosine 3′5′-Monophosphate (cGMP); Metabolic syndrome; Nitric oxide
3.  Effect of 6-months of physical exercise on the nitrate/nitrite levels in hypertensive postmenopausal women 
BMC Women's Health  2009;9:17.
Background
Evidences have showed that the incidence of arterial hypertension is greater in postmenopausal women as compared to premenopausal. Physical inactivity has been implicated as a major contributor to weight gain and abdominal obesity in postmenopausal women and the incidence of cardiovascular disease increases dramatically after menopause. Additionally, more women than men die each year of coronary heart disease and are twice as likely as men to die within the first year after a heart attack. A healthy lifestyle has been strongly associated with the regular physical activity and evidences have shown that physically active subjects have more longevity with reduction of morbidity and mortality. Nitric oxide (NO) produced by endothelial cells has been implicated in this beneficial effect with improvement of vascular relaxing and reduction in blood pressure in both laboratory animals and human. Although the effect of exercise training in the human cardiovascular system has been largely studied, the majority of these studies were predominantly conducted in men or young volunteers. Therefore, the aim of this work was to investigate the effects of 6 months of dynamic exercise training (ET) on blood pressure and plasma nitrate/nitrite concentration (NOx-) in hypertensive postmenopausal women.
Methods
Eleven volunteers were submitted to the ET consisting in 3 days a week, each session of 60 minutes during 6 months at moderate intensity (50% of heart rate reserve). Anthropometric parameters, blood pressure, NOx- concentration were measured at initial time and after ET.
Results
A significant reduction in both systolic and diastolic blood pressure values was seen after ET which was accompanied by markedly increase of NOx- levels (basal: 10 ± 0.9; ET: 16 ± 2 μM). Total cholesterol was significantly reduced (basal: 220 ± 38 and ET: 178 ± 22 mg/dl), whereas triglycerides levels were not modified after ET (basal: 141 ± 89 and ET: 147 ± 8 mg/dl).
Conclusion
Our study shows that changing in lifestyle promotes reduction of arterial pressure which was accompanied by increase in nitrite/nitrate concentration. Therefore, 6-months of exercise training are an important approach in management arterial hypertension and play a protective effect in postmenopausal women.
doi:10.1186/1472-6874-9-17
PMCID: PMC2714506  PMID: 19545388
4.  The Relationships Between Simulated Tennis Performance and Biomarkers for Nitric Oxide Synthesis 
Tennis performance requires a good aerobic endurance and recovering capacity. Nitric oxide (NO) is a gas which is not only a vasodilator and antioxidant but it also regulates the use of oxygen and glucose. The aim of this study was to examine the relationships between simulated tennis performance test (PT) and NOx (sum of nitrate+nitrite) levels and lactate elimination speed (LES). Twenty well trained male tennis players with game levels of ITN 4 (International Tennis Number) and lower (mean ± SD; age 22.9 ± 2.6 yrs; height 1.82 ± 0.06 m and mass 75.7 ± 8.0 kg) participated in the study. Participants performed three 4-min bouts and a 2-min continuous groundstroke against balls projected from a tennis ball machine at speeds of 50, 55, 62 and 70 km·h-1. After this exercise, subjects were given a 20 min passive rest. After each period and at during the recovery phase; plasma NOx, glucose (GLU) and lactate (LA) levels were determined. LES was calculated during passive recovery. GLU, LA and heart rate (HR) showed a linear increase in comparison to the values in the previous step while PT decreased significantly. Following each period NOx and glucose levels increased independently, but their decreasing rates in recovery phase were related (r = 0.470, p < 0.05). The successive increase in NOx and GLU parameters between the third and the forth periods was significant (p < 0.05). Only in the third period was there a significant relation between PT and NOx (r = 0.494; p < 0.05). In the present study, no significant relationship was found between PT and GLU, LA levels and LES. No significant correlation was found between simulated tennis performance and blood NOx levels. However the addition of loads like those in the third period in tennis trainings can be beneficial for performance in trained tennis players. It is recommended that the relationships between tennis performance with NOx and GLU are studied during a real tennis match.
Key PointsIn a sport like tennis which lasts 2-6 hours and has short rests, performance depends on the player’s capacity to perform the intensive exercise intermittently. Therefore, recovering potential is important in tennis.In none of the periods of this study were the expected (significant) relations observed of the athletes. Therefore, it can be claimed that LA increase, LA elimination and aerobic endurance do not play a significant role in the performance and the decrease in performance in this exercise model.
PMCID: PMC3761831  PMID: 24149805
Blood lactate; heart rate; nitric oxide; stroke performance; tennis
5.  Eicosapentaenoic Acid Supplementation Changes Fatty Acid Composition and Corrects Endothelial Dysfunction in Hyperlipidemic Patients 
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.
doi:10.1155/2012/754181
PMCID: PMC3541561  PMID: 23326753
6.  Relationship between circulating progenitor cells, vascular function and oxidative stress with long-term training and short-term detraining in older men 
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.
doi:10.1042/CS20090253
PMCID: PMC3160825  PMID: 19723023
aging; antioxidant; endothelial progenitor cell; exercise; forearm blood flow; physical inactivity
7.  Glycine propionyl-L-carnitine increases plasma nitrate/nitrite in resistance trained men 
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.
doi:10.1186/1550-2783-4-22
PMCID: PMC2211291  PMID: 18053183
8.  Plasma nitric oxide metabolite levels increase during successive exercise stress testing – A link to delayed ischemic preconditioning? 
BACKGROUND:
Animal studies have shown that nitric oxide is involved in delayed ischemic preconditioning.
OBJECTIVES:
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
METHODS:
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.
RESULTS:
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).
CONCLUSION:
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.
PMCID: PMC2716196  PMID: 19644584
Delayed preconditioning; Exercise; Nitrate; Nitric oxide; Nitrite
9.  Exercise Training, NADPH Oxidase p22phox Gene Polymorphisms, and Hypertension 
Introduction
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.
Methods
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).
Results
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.
Conclusions
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.
doi:10.1249/MSS.0b013e318199cee8
PMCID: PMC2871250  PMID: 19516159
OXIDATIVE STRESS; AEROBIC EXERCISE; CYBA GENE; NITRIC OXIDE; ISOPROSTANES
10.  Aerobic exercise training increases circulating IGFBP-1 concentration, but does not attenuate the reduction in circulating IGFBP-1 after a high-fat meal 
Metabolism  2011;61(3):310-316.
Rationale
Insulin-like growth factor binding protein-1 (IGFBP-1) has metabolic effects throughout the body and its expression is regulated in part by insulin. Circulating IGFBP-1 predicts development of cardiometabolic diseases in longitudinal studies and low IGFBP-1 concentrations are associated with insulin resistance and consumption of a high-fat diet. Because of the favorable metabolic effects of regular aerobic exercise, we hypothesized that aerobic exercise training would increase plasma IGFBP-1 concentrations and attenuate the reduction in IGFBP-1 after a high-fat meal.
Methods
Ten overweight (BMI=28.7±0.9kg/m2), older (61±2yr) men and women underwent high-fat feeding and oral glucose tolerance tests (OGTT) at baseline and after 6 months of aerobic exercise training.
Results
In response to aerobic exercise training, subjects increased cardiorespiratory fitness 13% (p<0.05) and insulin sensitivity index 28% (p<0.05). Basal plasma concentrations of IGFBP-1 increased 41% after aerobic exercise training (p<0.05). The insulin response to an OGTT was a significant predictor of fasting plasma IGFBP-1 concentrations at baseline and after exercise training (p=0.02). In response to the high-fat meal at baseline, plasma IGFBP-1 concentrations decreased 58% (p<0.001); a 61% decrease to similar postprandial concentrations was observed after exercise training (p<0.001). Plasma insulin response to the high-fat meal was inversely associated with postprandial IGFBP-1 concentrations at baseline and after exercise training (p=0.06 and p<0.05, respectively).
Conclusion
While aerobic exercise training did not attenuate the response to a high-fat meal, the increase in IGFBP-1 concentrations after exercise training may be one mechanism by which exercise reduces risk for cardiometabolic diseases in older adults.
doi:10.1016/j.metabol.2011.07.003
PMCID: PMC3227769  PMID: 21872284
insulin; glucose tolerance; lipemia; diet
11.  Muscle contraction duration and fibre recruitment influence blood flow and VO2 independent of contractile work during steady-state exercise in humans 
Experimental Physiology  2012;97(6):750-761.
We tested the hypothesis that, among conditions of matched contractile work, shorter contraction durations and greater muscle fibre recruitment result in augmented skeletal muscle blood flow and oxygen consumption (V̇O2) during steady-state exercise in humans. To do so, we measured forearm blood flow (FBF; Doppler ultrasound) during 4 minutes of rhythmic handgrip exercise in 24 healthy young adults and calculated forearm V̇O2 via blood samples obtained from a catheter placed in retrograde fashion into a deep vein draining the forearm muscle. In Protocol 1 (n = 11), subjects performed rhythmic isometric handgrip exercise at mild and moderate intensities under conditions in which tension time index (TTI; isometric analog of work) was held constant but contraction duration was manipulated. In this protocol, shorter contraction durations led to greater FBF (184 ± 25 vs. 164 ± 25 ml·min-1) and V̇O2 (23 ± 3 vs. 17 ± 2 ml·min-1; both P <0.05) among mild workloads, whereas this was not the case for moderate intensity exercise. In Protocol 2 (n = 13), subjects performed rhythmic dynamic handgrip exercise at mild and moderate intensities under conditions of matched total work, but muscle fibre recruitment was manipulated. In this protocol, greater muscle fibre recruitment led to significantly greater FBF (152 ± 15 vs. 127 ±13 ml·min-1) and V̇O2 (20 ± 2 vs. 17 ± 2 ml·min-1; both P<0.05) at mild workloads and there was a trend for similar responses at the moderate intensity but this was not statistically significant. In both protocols, the ratio of the change in FBF to change in V̇O2 was similar across all exercise intensities and manipulations, and the strongest correlation among all variables was between V̇O2 and blood flow. Our collective data indicate that, among matched workloads, shorter contraction duration and greater muscle fibre recruitment augment FBF and V̇O2 during mild intensity forearm exercise, and that muscle blood flow is more closely related to metabolic cost (V̇O2) rather than contractile work per se during steady-state exercise in humans.
doi:10.1113/expphysiol.2011.062968
PMCID: PMC3366163  PMID: 22327330
vasodilatation; metabolic cost; oxygen delivery
12.  Effects of atorvastatin on reactive hyperaemia and the thrombosis–fibrinolysis system in patients with heart failure 
Heart  2005;91(1):27-31.
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.
doi:10.1136/hrt.2003.027110
PMCID: PMC1768647  PMID: 15604328
heart failure; statins; endothelium; thrombosis; fibrinolysis
13.  Acute L-Arginine supplementation does not increase nitric oxide production in healthy subjects 
Dietary supplements containing L-arginine have been marketed with the purpose of increasing vasodilatation, and thus, blood and oxygen supply to the exercising muscle. The present study evaluated the acute effect of L-arginine supplementation on indicators of NO production, nitrite (NO2-) + nitrate (NO3-) (NOx), in healthy subjects. Plasma concentrations of asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) have also been addressed. Seventeen healthy males participated in a randomized, double-blind, placebo-controlled study. Blood samples were drawn from a left antecubital vein at baseline (T0). Afterwards, subjects were randomly submittedto 6 g of oral L-arginine supplementation (as L-arginine hydrochloride) or placebo (as corn starch); afterwards, the subjects remained at rest in supine position and blood samples were drawn again at 30 (T1), 60 (T2), 90 (T3) and 120 minutes (T4) after supplementation. To analyze NO production, NO3- was converted to NO2- by nitrate reductase, followed by the derivatization of NO2- with 2,3-diaminonaphthalene. NOx, ADMA and SDMA were analyzed using a high-performance liquid chromatography system and monitored with a fluorescence detector. Two-way ANOVA with repeated measures showed no significant changes in NOx concentrations on the L-arginine group as compared to placebo group at any of the fivetime points (T0: 17.6 ± 3.9 vs 14.6 ± 2.3 μmol/L; T1: 15.8 ± 2.4 vs 14.3 ± 1.7 μmol/L; T2: 16.8 ± 4.9 vs 13.7 ± 2.7 μmol/L; T3: 16.7 ± 3.9 vs 14.6 ± 2.1 μmol/L; T4: 15.1 ± 2.8 vs 13.5 ± 3.5 μmol/L). Furthermore, plasma levels of ADMA and SDMA were not statistically significant between the L-arginine and placebo groups at T0 (0.43 ± 0.19 vs 0.39 ± 0.15 μmol/L and 1.83 ± 1.13 vs 1.70 ± 0.62 μmol/L), respectively. In conclusion, acute L-arginine supplementation does not increase plasma concentration of NOx in healthy individuals with normal plasma concentrations of ADMA.
doi:10.1186/1743-7075-9-54
PMCID: PMC3489573  PMID: 22691607
Amino acids; Nitric oxide; Asymmetric dimethylarginine; Symmetric dimethylarginine; Nitrite; Nitrate; HPLC
14.  Effects of Six Months of Combined Aerobic and Resistance Training for Elderly Patients with a Long History of Type 2 Diabetes 
This study evaluated the effects of a 6-month combined aerobic and resistance training program on the body composition, glycemic control, lipid profile, and functional capacity of older patients with a long history of type 2 diabetes. 25 subjects (65.9 ± 4. 2 yrs; M/F: 13/12) with a long history of type 2 diabetes (16.7 ± 6.7 yrs) were randomly allocated into either the exercise or control groups. The exercise group trained three sessions a week. Each session consisted of a warm-up period, 30 minutes of moderate aerobic exercise, 10 minutes of resistance training with five leg muscle exercises (two sets of 10-12 repetitions at 50-70% of 1RM for each activity), and a cool-down period. The variables of body composition, glycemic control, lipid profile, and functional capacity were measured before and after the study period. Exercise training decreased waist-hip ratio and body fat of the trained subjects. Concentrations of fasting and 2-hour post-glucose challenge plasma glucose and serum insulin, and glycosylated hemoglobin decreased significantly in the exercise group. Exercise training improved the lipid profile and also increased the leg muscle strength and 6-minute walking distance of the trained subjects. The control group, however, increased their body fat and fasting plasma glucose, while other variables were not changed during the study period. The current results demonstrate that elderly patients with a long history of type 2 diabetes can benefit from the 6-month combined aerobic and resistance training program.
Key pointsExercise training is effective for elderly patients with long-term type 2 diabetesExercise prescription for elderly patients with type 2 diabetes should contain both aerobic and resistance activities
PMCID: PMC3737933  PMID: 24149359
Type 2 diabetes; exercise training; glycemic control; lipid profile; functional capacity
15.  The effects of pre- and post-exercise consumption of multi-ingredient performance supplements on cardiovascular health and body fat in trained men after six weeks of resistance training: a stratified, randomized, double-blind study 
Background
The cardiovascular (CV) and metabolic health benefits or risks associated with consumption of multi-ingredient performance supplements (MIPS) in conjunction with periodized resistance training (RT) in resistance-trained men are unknown. This population is a major target audience for performance supplements, and therefore, the purpose of this study was to investigate the combined effect of RT and commercially available pre- and post-exercise performance supplements on CV health and body fat in resistance-trained men.
Methods
Twenty-four resistance-trained men completed six weeks (three times/week) of periodized RT while either ingesting SHOT 15-min pre-exercise and SYN immediately post-exercise (multi-ingredient performance supplement group: MIPS) or an isocaloric maltodextrin placebo 15-min pre-exercise and immediately post-exercise (Placebo group). Before and after six weeks of RT and supplementation, resting heart rate (HR), blood pressure (BP), total body fat, android fat, gynoid fat, fat-free mass (FFM) and fasting blood measures of glucose, lipids, nitrate/nitrite (NOx), cortisol and high sensitivity C-reactive protein (hs-CRP) were measured. Statistical analysis was conducted using a one-way ANOVA for baseline differences and a 2 × 2 (group × time) repeated measures ANOVA and Tukey post-hoc tests where appropriate. Significance was set at p < 0.05.
Results
There was no group × time interaction for HR, BP, blood glucose, lipids, NOx, hs-CRP, cortisol concentrations or body fat. However, there was a time effect where significant decreases in body fat (mean ± SD; MIPS: -1.2 ± 1.2%; Placebo: -0.9 ± 1.1%), android fat (MIPS: -1.8 ± 2.1%; Placebo: -1.6 ± 2.0%), and gynoid fat (MIPS: -1.3 ± 1.6%; Placebo: -1.0 ± 1.4%) for both groups were observed. FFM increased in both groups, and a group × time interaction was observed with MIPS increasing significantly more than the Placebo group (4.2% vs. 1.9%).
Conclusions
Six weeks of MIPS ingestion and periodized RT does not alter CV health parameters or blood indices of health or body fat more than a Placebo treatment in healthy, resistance-trained men. However, MIPS significantly increased FFM more than Placebo.
doi:10.1186/1743-7075-10-39
PMCID: PMC3662597  PMID: 23680036
Weight lifting; Supplementation; Regional body fat; Fat-free mass; Health
16.  Muscle-Strengthening and Conditioning Activities and Risk of Type 2 Diabetes: A Prospective Study in Two Cohorts of US Women 
PLoS Medicine  2014;11(1):e1001587.
Anders Grøntved and colleagues examined whether women who perform muscle-strengthening and conditioning activities have an associated reduced risk of type 2 diabetes mellitus.
Please see later in the article for the Editors' Summary
Background
It is well established that aerobic physical activity can lower the risk of type 2 diabetes (T2D), but whether muscle-strengthening activities are beneficial for the prevention of T2D is unclear. This study examined the association of muscle-strengthening activities with the risk of T2D in women.
Methods and Findings
We prospectively followed up 99,316 middle-aged and older women for 8 years from the Nurses' Health Study ([NHS] aged 53–81 years, 2000–2008) and Nurses' Health Study II ([NHSII] aged 36–55 years, 2001–2009), who were free of diabetes, cancer, and cardiovascular diseases at baseline. Participants reported weekly time spent on resistance exercise, lower intensity muscular conditioning exercises (yoga, stretching, toning), and aerobic moderate and vigorous physical activity (MVPA) at baseline and in 2004/2005. Cox regression with adjustment for major determinants for T2D was carried out to examine the influence of these types of activities on T2D risk. During 705,869 person years of follow-up, 3,491 incident T2D cases were documented. In multivariable adjusted models including aerobic MVPA, the pooled relative risk (RR) for T2D for women performing 1–29, 30–59, 60–150, and >150 min/week of total muscle-strengthening and conditioning activities was 0.83, 0.93, 0.75, and 0.60 compared to women reporting no muscle-strengthening and conditioning activities (p<0.001 for trend). Furthermore, resistance exercise and lower intensity muscular conditioning exercises were each independently associated with lower risk of T2D in pooled analyses. Women who engaged in at least 150 min/week of aerobic MVPA and at least 60 min/week of muscle-strengthening activities had substantial risk reduction compared with inactive women (pooled RR = 0.33 [95% CI 0.29–0.38]). Limitations to the study include that muscle-strengthening and conditioning activity and other types of physical activity were assessed by a self-administered questionnaire and that the study population consisted of registered nurses with mostly European ancestry.
Conclusions
Our study suggests that engagement in muscle-strengthening and conditioning activities (resistance exercise, yoga, stretching, toning) is associated with a lower risk of T2D. Engagement in both aerobic MVPA and muscle-strengthening type activity is associated with a substantial reduction in the risk of T2D in middle-aged and older women.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Worldwide, more than 370 million people have diabetes mellitus, a disorder characterized by poor glycemic control—dangerously high amounts of glucose (sugar) in the blood. Blood sugar levels are normally controlled by insulin, a hormone released by the pancreas. In people with type 2 diabetes (the commonest form of diabetes), blood sugar control fails because the fat and muscle cells that normally respond to insulin by removing excess sugar from the blood become less responsive to insulin. Type 2 diabetes, which was previously known as adult-onset diabetes, can often initially be controlled with diet and exercise, and with antidiabetic drugs such as metformin and sulfonylureas. However, as the disease progresses, the pancreatic beta cells, which make insulin, become impaired and patients may eventually need insulin injections. Long-term complications of diabetes, which include an increased risk of cardiovascular problems such as heart disease and stroke, reduce the life expectancy of people with diabetes by about 10 years compared to people without diabetes.
Why Was This Study Done?
Type 2 diabetes is becoming increasingly common worldwide so better preventative strategies are essential. It is well-established that regular aerobic exercise—physical activity in which the breathing and heart rate increase noticeably such as jogging, brisk walking, and swimming—lowers the risk of type 2 diabetes. The World Health Organization currently recommends that adults should do at least 150 min/week of moderate-to-vigorous aerobic physical activity to reduce the risk of diabetes and other non-communicable diseases. It also recommends that adults should undertake muscle-strengthening and conditioning activities such as weight training and yoga on two or more days a week. However, although studies have shown that muscle-strengthening activity improves glycemic control in people who already have diabetes, it is unclear whether this form of exercise prevents diabetes. In this prospective cohort study (a study in which disease development is followed up over time in a group of people whose characteristics are recorded at baseline), the researchers investigated the association of muscle-strengthening activities with the risk of type 2 diabetes in women.
What Did the Researchers Do and Find?
The researchers followed up nearly 100,000 women enrolled in the Nurses' Health Study (NHS) and the Nurses' Health Study II (NHSII), two prospective US investigations into risk factors for chronic diseases in women, for 8 years. The women provided information on weekly participation in muscle-strengthening exercise (for example, weight training), lower intensity muscle-conditioning exercises (for example, yoga and toning), and aerobic moderate and vigorous physical activity (aerobic MVPA) at baseline and 4 years later. During the study 3,491 women developed diabetes. After allowing for major risk factors for type 2 diabetes (for example, diet and a family history of diabetes) and for aerobic MVPA, compared to women who did no muscle-strengthening or conditioning exercise, the risk of developing type 2 diabetes among women declined with increasing participation in muscle-strengthening and conditioning activity. Notably, women who did more than 150 min/week of these types of exercise had 40% lower risk of developing diabetes as women who did not exercise in this way at all. Muscle-strengthening and muscle-conditioning exercise were both independently associated with reduced diabetes risk, and women who engaged in at least 150 min/week of aerobic MVPA and at least 60 min/week of muscle-strengthening exercise were a third as likely to develop diabetes as inactive women.
What Do These Findings Mean?
These findings show that, among the women enrolled in NHS and NHSII, engagement in muscle-strengthening and conditioning activities lowered the risk of type 2 diabetes independent of aerobic MVPA. That is, non-aerobic exercise provided protection against diabetes in women who did no aerobic exercise. Importantly, they also show that doing both aerobic exercise and muscle-strengthening exercise substantially reduced the risk of type 2 diabetes. Because nearly all the participants in NHS and NHSII were of European ancestry, these results may not be generalizable to women of other ethnic backgrounds. Moreover, the accuracy of these findings may be limited by the use of self-administered questionnaires to determine how much exercise the women undertook. Nevertheless, these findings support the inclusion of muscle-strengthening and conditioning exercises in strategies designed to prevent type 2 diabetes in women, a conclusion that is consistent with current guidelines for physical activity among adults.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001587.
The US National Diabetes Information Clearinghouse provides information about diabetes for patients, health-care professionals and the general public, including information on diabetes prevention (in English and Spanish)
The UK National Health Service Choices website provides information for patients and carers about type 2 diabetes and explains the benefits of regular physical activity
The World Health Organization provides information about diabetes and about physical activity and health (in several languages); its 2010 Global Recommendations on Physical Activity for Health are available in several languages
The US Centers for Disease Control and Prevention provides information on physical activity for different age groups; its Physical Activity for Everyone web pages include guidelines, instructional videos and personal success stories
More information about the Nurses Health Study and the Nurses Health Study II is available
The UK charity Healthtalkonline has interviews with people about their experiences of diabetes
MedlinePlus provides links to further resources and advice about diabetes and about physical exercise and fitness (in English and Spanish)
doi:10.1371/journal.pmed.1001587
PMCID: PMC3891575  PMID: 24453948
17.  Long-term exercise training in overweight adolescents improves plasma peptide YY and resistin 
Obesity (Silver Spring, Md.)  2009;17(6):10.1038/oby.2009.11.
The objective of this study was to investigate the effect of long-term exercise training on concentrations of five hormones related to appetite and insulin resistance in overweight adolescents. Additionally, we were interested in the relationships of these hormones with each other and with anthropometric and/or cardiovascular disease marker changes. Participants were ≥ the 85th percentile for body mass index for age and sex and participated in an eight month supervised aerobic training program. Anthropometrics, cardiovascular fitness assessment, and fasting blood samples were taken pre- and post-training. Glucose, insulin, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, leptin, active ghrelin, total peptide YY (PYY), adiponectin, and resistin concentrations were measured. The participants increased their time to exhaustion on an incremental treadmill test and decreased both percent body fat and blood triglyceride concentrations. Total PYY concentration increased and resistin concentration decreased after long-term exercise training, which are favorable outcomes. Leptin concentrations were related to weight, percent body fat, waist circumference, and triglyceride concentrations pre- and post-training. The changes in resistin concentrations were related to the changes in triglyceride concentrations. We conclude that long-term exercise training has beneficial effects for overweight adolescents with respect to PYY and resistin, hormones related to appetite and insulin sensitivity.
doi:10.1038/oby.2009.11
PMCID: PMC3845441  PMID: 19247279
18.  The Effects of Aerobic Versus Resistance Training on Cardiovascular Fitness in Obese Sedentary Females 
Asian Journal of Sports Medicine  2010;1(4):177-184.
Purpose
The present study was designed to evaluate the effects of aerobic and strength training on cardiac variables such as blood pressure, heart rate (HR), and metabolic parameters like cholesterol, high density lipoprotein (HDL), triglycerides and anthropometric parameters of obese women of Punjab.
Methods
This study was performed as an experimental study, in which subjects were randomly selected. There were thirty obese women, aged between 35-45yrs with body mass index (BMI) of above 30. Subjects were grouped into control (n=10), aerobic training (n=10) and resistance training (n=10). Aerobic training was given for three days a week at 60-70% of maximum HR for 6 weeks. Resistance training (Delorme and Watkins Technique) was given for alternate days for 6 weeks. HR and blood pressure were measured before and after the exercise. Recovery HR was also measured.
Results
The findings of the study indicate statistically significant differences in recovery heart rate [Pre-exercise: 97.40± 5.378 (mean±standard deviation (SD)), post-exercise: 90.70±4.599, t=8.066, P<0.001] and in post-diastolic blood pressure [Pre-exercise: 85±3.265, post-exercise: 86.20±2.820, P<0.001] in aerobic training and in systolic blood pressure [Pre- and post-exercise] in both training groups (P<0.001). Significant differences were observed in very low-density lipoprotein [pre-exercise: 28.10±1.415, post-exercise: 26.86±0.760, t=5.378] and HDL [pre-exercise: 45.40±3.533, post-exercise: 53.60±3.134, t=6.318] levels in aerobic training group with P<0.001. BMI and body fat percentage showed significant improvements in both training groups.
Conclusion
Aerobic training is more beneficial and can be used as a preventive measure in patients who are at risk of developing cardiovascular diseases due to obesity.
PMCID: PMC3289184  PMID: 22375205
Aerobic exercise; Resistance training; Obesity; Heart rate; Physical fitness
19.  Effects of Exercise on Oxidative Stress in Rats Induced by Ozone 
The Scientific World Journal  2012;2012:135921.
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.
doi:10.1100/2012/135921
PMCID: PMC3349314  PMID: 22619585
20.  Effects of combined exercise on cardiovascular risk factors and serum BDNF level in mid-aged women 
[Purpose]
The purposes of this study is first to examine a positive effect of long term combined exercise including aerobic and resistance exercise on increasing level of serum BDNF, and investigate how aerobic exercise is related to improving BDNF circulation and resistance exercise improves fat oxidation in mid-aged women.
[Methods]
Initially, 30 mid-aged women, according to their exercise preference, was randomly assigned as a non-exercise group (n=7, control group; CG) and exercise group (n=23). Then, 23 exercise participants were divided by aerobic exercise group (n=15, AEG) and combination of aerobic and resistance exercise group (n=8, CEG). Prior to the experiment, all participants’maximal oxygen uptake (VO2max), body composition, and blood factors were measured. Changes (Δ delta value) in body composition, fitness level, and serum BDNF level of the different groups were tested through one way ANOVA.
[Results]
For AEG and CG after 24 weeks, VO2max and high-density lipoprotein cholesterol (HDL-C) were significantly increased. During this period, CEG had significant increase in muscular strength and decrease in triglyceride (TG) total cholesterol (TC)/HDL-C (p=0.013). Continuously, serum BDNF concentration of both AEG and CEG was significantly increased (F=6.328, p=0.001) compared to CG. There, however, was no significant between-group difference.
[Conclusion]
Although there was no difference in serum BDNF level between AEG and CEG, we confirmed that CEG may have a possibility of positive changes in increase of serum BDNF level in mid-aged women.
doi:10.5717/jenb.2014.18.1.61
PMCID: PMC4241931  PMID: 25566440
aerobic exercise; resistance exercise; oxygen uptake; muscle fitness; body composition
21.  Vasodilatory actions of alpha-human atrial natriuretic peptide and high Ca2+ effects in normal man. 
Journal of Clinical Investigation  1987;80(3):832-840.
To study vascular actions of synthetic alpha-human atrial natriuretic polypeptide (alpha hANP) in man, forearm blood flow (FBF) was measured by strain-gauge plethysmograph during the continuous infusion of 100 ng/min alpha hANP dissolved in 5% dextrose into the brachial artery in healthy subjects. alpha hANP increased FBF, with the concomitant increase in ipsilateral limb venous plasma concentrations of alpha hANP. Overall, there was a significant linear correlation between the decrements of ipsilateral forearm vascular resistance (FVR) during infusions of alpha hANP and initial FVR levels (r = -0.883, P less than 0.01). Moreover, alpha hANP, at the stepwise increasing doses of 20, 100, and 500 ng/min, increased FBF in a dose-related fashion: alpha hANP elicits a concentration-dependent vasodilation of forearm vascular beds. Concomitantly, infusions of alpha hANP caused a dose-dependent increase in ipsilateral limb venous plasma cyclic guanosine monophosphate (cyclic GMP). Overall, there were direct correlations of FBF either to ipsilateral venous plasma alpha hANP (r = 0.724, P less than 0.01) or to cyclic GMP concentrations (r = 0.637, P less than 0.01). Subsequently, isoosmolar CaCl2 solution was infused into the same brachial artery at a rate of 0.09 meq/min, and then, with a 2.5 +/- 0.2-mg/dl increase in ipsilateral venous serum calcium concentrations the incremental responses of both FBF and plasma cyclic GMP to alpha hANP were severely blunted. There was also a significant positive linear correlation between FBF and venous plasma cyclic GMP during infusions of alpha hANP with the simultaneous administration of CaCl2 (r = 0.807, P less than 0.01). Finally, the addition of CaCl2 infusion did not change the slope of the regression line of the FBF-plasma cyclic GMP relationship during infusions of alpha hANP. Evidence presented suggests that alpha hANP acts directly on the forearm vascular beds in man, eliciting its vascular relaxant effect, possibly by increasing cellular levels of cyclic GMP. Moreover, modest elevations of serum calcium inhibit the alpha hANP-dependent vasodilation, possibly through the suppression of cyclic GMP activation.
PMCID: PMC442310  PMID: 3040808
22.  Comparison of pre-workout nitric oxide stimulating dietary supplements on skeletal muscle oxygen saturation, blood nitrate/nitrite, lipid peroxidation, and upper body exercise performance in resistance trained men 
Background
We compared Glycine Propionyl-L-Carnitine (GlycoCarn®) and three different pre-workout nutritional supplements on measures of skeletal muscle oxygen saturation (StO2), blood nitrate/nitrite (NOx), lactate (HLa), malondialdehyde (MDA), and exercise performance in men.
Methods
Using a randomized, double-blind, cross-over design, 19 resistance trained men performed tests of muscular power (bench press throws) and endurance (10 sets of bench press to muscular failure). A placebo, GlycoCarn®, or one of three dietary supplements (SUPP1, SUPP2, SUPP3) was consumed prior to exercise, with one week separating conditions. Blood was collected before receiving the condition and immediately after exercise. StO2 was measured during the endurance test using Near Infrared Spectroscopy. Heart rate (HR) and rating of perceived exertion (RPE) were determined at the end of each set.
Results
A condition effect was noted for StO2 at the start of exercise (p = 0.02), with GlycoCarn® higher than SUPP2. A condition effect was also noted for StO2 at the end of exercise (p = 0.003), with SUPP1 lower than all other conditions. No statistically significant interaction, condition, or time effects were noted for NOx or MDA (p > 0.05); however, MDA decreased 13.7% with GlycoCarn® and increased in all other conditions. Only a time effect was noted for HLa (p < 0.0001), with values increasing from pre- to post-exercise. No effects were noted for HR, RPE, or for any exercise performance variables (p > 0.05); however, GlycoCarn® resulted in a statistically insignificant greater total volume load compared to the placebo (3.3%), SUPP1 (4.2%), SUPP2 (2.5%), and SUPP3 (4.6%).
Conclusion
None of the products tested resulted in favorable changes in our chosen outcome measures, with the exception of GlycoCarn® in terms of higher StO2 at the start of exercise. GlycoCarn® resulted in a 13.7% decrease in MDA from pre- to post-exercise and yielded a non-significant but greater total volume load compared to all other conditions. These data indicate that 1) a single ingredient (GlycoCarn®) can provide similar practical benefit than finished products containing multiple ingredients, and 2) while we do not have data in relation to post-exercise recovery parameters, the tested products are ineffective in terms of increasing blood flow and improving acute upper body exercise performance.
doi:10.1186/1550-2783-7-16
PMCID: PMC2876074  PMID: 20459623
23.  Heterogeneous vascular responses to hypoxic forearm exercise in young and older adults 
European journal of applied physiology  2011;112(8):3087-3095.
We aimed to assess age-related differences in compensatory hypoxic vasodilation during moderate-to-high dynamic exercise at absolute workloads. We hypothesized healthy older adults (n = 12, 61 ± 1 years) would exhibit impaired hypoxic vasodilation at a moderate absolute workload, and this effect would be exaggerated at a higher workload when compared to young adults (n = 17, 27 ± 2 years). Forearm blood flow (FBF) was measured with Doppler ultrasound. Dynamic forearm exercise (20 contractions/min) was completed at two absolute workloads (8 and 12 kg) under normoxic (0.21 FiO2, ~98% SpO2) and isocapnic hypoxic (~0.10 FiO2, 80% SpO2) conditions performed in random order. FBF was normalized as forearm vascular conductance (FBF / mean arterial blood pressure = FVC) to control for differences in blood pressure and to assess vasodilation. FVC increased with exercise and hypoxia (main effects, p < 0.05); vascular responses were not different between young and older adults (interaction effect exercise × group p = 0.37 and hypoxia × group p = 0.96). Results were confirmed when analyzed as either an absolute or relative change in FVC (ΔFVC and %ΔFVC, respectively). Although group responses to hypoxia were not different, individual results were highly variable (i.e., some adults constricted and others dilated to hypoxia). These data suggest (1) compensatory hypoxic vasodilation in older adults is not impaired during forearm exercise at both moderate and higher absolute exercise intensities, and (2) vascular responses to hypoxia are heterogeneous in both young and older adults. Results suggest unique individual differences exist in factors regulating vascular responses to hypoxia.
doi:10.1007/s00421-011-2280-x
PMCID: PMC4158744  PMID: 22198326
Aging; Functional hyperemia; Blood flow
24.  Atorvastatin Increases Exercise Leg Blood Flow in Healthy Adults 
Atherosclerosis  2011;219(2):768-773.
OBJECTIVES
We sought to examine the effect of atorvastatin therapy on exercise leg blood flow in healthy middle-aged and older, men and women.
BACKGROUND
The vasodilatory response to exercise decreases in humans with aging and disease and this reduction may contribute to reduced exercise capacity.
METHODS
We used a double-blind, randomly assigned, placebo-controlled protocol to assess the effect of atorvastatin treatment on exercising leg hemodynamics. We measured femoral artery blood flow (FBF) using Doppler ultrasound and calculated femoral vascular conductance (FVC) from brachial mean arterial pressure (MAP) before and during single knee-extensor exercise in healthy adults (ages 40–71) before (PRE) and after (POST) 6 months of 80 mg atorvastatin (A: 14 men, 16 women) or placebo (P: 14 men, 22 women) treatment. FBF and FVC were normalized to exercise power output and estimated quadriceps muscle mass.
RESULTS
Atorvastatin reduced LDL cholesterol by approximately 50%, but not in the placebo group (p < 0.01). Atorvastatin also increased exercise FBF from 44.2 ± 19.0 to 51.4 ± 22.0 mL/min/W/kg muscle whereas FBF in the placebo group was unchanged (40.1 ± 16.0 vs 39.5 ± 16.1) (p <0.01). FVC also increased with atorvastatin from 0.5 ± 0.2 to. 0.6 ± 0.2 mL/min/mmHg/W/kg muscle, but not in the placebo subjects (P: 0.4 ± 0.2 vs 0.4 ± 0.2) ( p < 0.01).
CONCLUSIONS
High-dose atorvastatin augments exercising leg hyperemia. Statins may mitigate reductions in the exercise vasodilatory response in humans that are associated with aging and disease.
doi:10.1016/j.atherosclerosis.2011.09.049
PMCID: PMC3226851  PMID: 22018642
Atorvastatin; leg vasodilation; exercise hyperemia
25.  Impact of diet, exercise end diet combined with exercise programs on plasma lipoprotein and adiponectin levels in obese girls 
We studied the effect of three programs, diet restriction (D), individualized exercise training (E) at the maximal lipid oxidation point (LIPOXmax) and diet combined with exercise (D+E), on body mass, plasma lipoprotein and adiponectin levels in obese girls. Eighteen obese adolescents girls aged 12-14 years were studied. A longitudinal intervention was carried out, consisting of a two-month diet (D; -500 kcal·day-1), of individualized exercise (E; 4 days/week, 90 min·day-1) and of diet combined with exercise (D+E). Body mass, body mass index (BMI), body fat mass, waist circumference, substrate crossover point, LIPOXmax point, homeostasis model assessment (HOMA-IR) index, fasting levels of lipids and circulatory adiponectin, were measured in all subjects before and after the program. In subjects of the D+E group, body mass, BMI, body fat mass, waist circumference, HOMA-IR, low-density lipoprotein cholesterol (LDL-C) and total cholesterol / high-density lipoprotein cholesterol (TC/HDL-C) ratio were significantly lower, and HDL-C and adiponectin were higher after the program than that of subjects in the D or E groups. Diet/exercise improved the ability to oxidize lipids during exercise (crossover point: + 18.5 ± 3.4 of % Wmax; p < 0.01 and fat oxidation rate at LIPOXmax: + 89.7 ± 19.7 mg·min-1; p < 0.01). In the D+E group, significant correlations were found between changes in body mass and adiponectin and between changes in the TC/HDL-C ratio and LIPOXmax. These findings show that the combined program of diet restriction and individualized exercise training at the LIPOXmax point is necessary to simultaneously improve body mass loss, adiponectin levels, as well as metabolic parameters, in obese girls.
Key pointsDiet combined with exercise training improved body composition, adiponectin levels and metabolic parameters in obese girls.Diet only decreases body mass and LDL-C without improving fat oxidation and HDL- C.Individualized exercise training at LIPOXmax point improved the HDL-C and the circulatory adiponectin levels with any change of LDL-C and body composition.
PMCID: PMC3761909  PMID: 24149948
Obese girls; lipoprotein; adiponectin; exercise training; diet restriction

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