Peripheral arterial disease (PAD) results in a failure to adequately supply blood and oxygen (O(2)) to working tissues and presents as claudication pain during walking. Nitric oxide (NO) bioavailability is essential for vascular health and function. Plasma nitrite (NO(2)(-)) is a marker of vascular NO production but may also be a protected circulating "source" that can be converted to NO during hypoxic conditions, possibly aiding perfusion. We hypothesized that dietary supplementation of inorganic nitrate in the form of beetroot (BR) juice would increase plasma NO(2)(-) concentration, increase exercise tolerance, and decrease gastrocnemius fractional O(2) extraction, compared with placebo (PL). This was a randomized, open-label, crossover study. At each visit, subjects (n = 8) underwent resting blood draws, followed by consumption of 500 ml BR or PL and subsequent blood draws prior to, during, and following a maximal cardiopulmonary exercise (CPX) test. Gastrocnemius oxygenation during the CPX was measured by near-infrared spectroscopy. There were no changes from rest for [NO(2)(-)] (152 ± 72 nM) following PL. BR increased plasma [NO(2)(-)] after 3 h (943 ± 826 nM; P ≤ 0.01). Subjects walked 18% longer before the onset of claudication pain (183 ± 84 s vs. 215 ± 99 s; P ≤ 0.01) and had a 17% longer peak walking time (467 ± 223 s vs. 533 ± 233 s; P ≤ 0.05) following BR vs. PL. Gastrocnemius tissue fractional O(2) extraction was lower during exercise following BR (7.3 ± 6.2 vs. 10.4 ± 6.1 arbitrary units; P ≤ 0.01). Diastolic blood pressure was lower in the BR group at rest and during CPX testing (P ≤ 0.05). These findings support the hypothesis that NO(2)(-)-related NO signaling increases peripheral tissue oxygenation in areas of hypoxia and increases exercise tolerance in PAD.

Purpose:The effect of exercise intensity on the tracking of serum and salivary cortisol responses was examined in 12 endurance-trained males (maximal oxygen uptake [VO2max] = 58.2 ± 6.4 mL/kg/min).Methods:Subjects rested for 30 min (control) and exercised on a cycle ergometer for 30 min at 40% (low), 60% (moderate), and 80% (high intensity) of VO2max on separate days. Serum and saliva samples were collected pretrial, immediately posttrial, and 30 min into the recovery period from each trial.Results:Cortisol responses increased significantly for both serum (40.4%; P = .001) and saliva (170.6%; P = .007) only in response to high-intensity exercise. Peak saliva cortisol occurred at 30 min of recovery, whereas peak serum was at the immediate posttrial sampling time point. The association between serum and saliva cortisol across all trials was examined using concordance correlation (Rc) analysis, which accounts for repeated measures. The overall correlation between serum and saliva cortisol levels in all matched samples was significant (Rc = 0.728; P = .001). The scatter plot revealed that salivary cortisol responses tracked closely to those of serum at lower concentrations, but not as well at higher concentrations.Conclusions:Findings suggest salivary measurements of cortisol closely mirror those in the serum and that peak salivary concentrations do not occur until at least 30 min into the recovery from intense exercise.

Rationale A primary goal of therapy for patients with peripheral arterial disease and intermittent claudication (PAD+IC) is increased ambulatory function. Supervised exercise rehabilitation was recently shown to confer superior walking benefits to pharmacological or surgical interventions. Increases in plasma inorganic nitrite, via oral nitrate, have been shown to increase exercise performance in both human and animal models, especially in hypoxic conditions. Objective To determine whether a 36-session exercise rehabilitation program while consuming oral inorganic nitrate (4.2mmol concentrated beetroot juice- EX+BR) would produce superior benefits over exercise plus placebo (EX+PL) in pain free walking and markers of increased skeletal muscle perfusion in patients with PAD+IC. Methods and Results This was a randomized, double-blind, per-protocol study design. Following the 12-week protocol claudication onset time (COT) on a maximal treadmill test increased by 59.2±57.3 sec for the EX+PL group (n=13), and by 180.3±46.6 sec for the EX+BR group (n=11) (p≤0.05). This produced a between treatment medium to large standardized effect size (Cohen’s d) of 0.62 (95%CI = −0.23 to +1.44). The data for six minute walk (6MW) distance showed a similar pattern with increases of 24.6±12.1 m and 53.3±19.6 m (p≤0.05) in the EX+PL and EX+BR groups respectively. Measures of gastrocnemius perfusion including ABI, peak reactive hyperemic blood flow and tissue deoxygenation characteristics during exercise (assessed my near infra-red spectroscopy) all changed significantly for the EX+BR group with moderate to large effect sizes over EX+PL changes. Conclusions While it is premature to speculate on overall clinical utility of a nitrate based therapy for PAD, this early pilot study evidence is encouraging. Specifically, our data suggests that increasing plasma nitrite prior to exercise may allow PAD subjects to train with less pain, at higher workloads for longer durations at each training session thereby maximizing the beneficial peripheral vascular and skeletal muscle adaptations. Clinical Trial Registration (NCT01684930, NCT01785524).

Advancing age is associated with an increase in physical impairment, functional limitations, disability, and loss of independence. Regular physical activity conveys health benefits, but the yield on physical function in the elderly, is less clear. Current exercise guidelines are focused predominantly on aerobic programs despite evidence that age-associated declines are mediated by peripheral tissue changes. The Fit for Life trial proposes a new paradigm of exercise training for the elderly that uses a low-mass high-repetition training regimen specifically focused on peripheral tissue beds or body regions (Regional Specific Training Stimulus-RSTS). RSTS is designed to deliver a localized stimulus to the peripheral vasculature, bone and muscle, without imposing a significant central cardiorespiratory strain. The purpose of this study is three-fold; 1) derive effect sizes from the RSTS intervention by which to power a subsequent larger, confirmatory trial; 2) assess fidelity of the RSTS intervention; 3) to assess the interrelationship of the primary endpoints of physical impairment/fitness (VO2peak, 1 repetition maximal contraction) and function (Senior Fitness Test scores) following two versions of a 4 + 8 week protocol Men and women over 70 years, at risk for losing independence will be randomized to either 4 weeks of RSTS or “aerobic” exercise, followed by an identical 8 weeks of progressive whole-body training (aerobic plus resistance). The guiding hypothesis is that the magnitude of adaptation after 12 weeks will be greatest in those initially randomized to RSTS. Possible mediators of the intervention effect - physical impairment/fitness and function relationship, including vascular function, muscle mass, strength, and physiology will also be assessed.

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Objective: Evaluate hormonal responses to incremental-stage exercise (EX) test to exhaustion in adolescents. Subjects and methods: Adolescents were tested at 16 years of age in Tanner Stage 4 (TS4) and at 17 years of age in Tanner Stage 5 (TS5) (n = 6). Adults were tested at 21 ± 1 y. (X ± SD) (n = 4) and served as controls. Blood samples were taken at rest, at the end of each EX stage. Results: Main effects for EX in cortisol (p < 0.01, increasing with each EX stage) and for subject group for testosterone (T) occurred (p < 0.01; TS4 < TS5, adults). Interaction effect of group by EX stage occurred for GH (p < 0.05). GH increased in response to EX in all groups, however, the magnitude of increase was significantly less for TS5 and adults than TS4. Conclusions: Differences in T and GH responses for TS4 than those for TS5 and adults reflect the differing maturation levels of the endocrine system between Tanner Stages. TS5 adolescents are more similar to young adults in hormonal responses to EX than are TS4 adolescents. Arq Bras Endocrinol Metab. 2011;55(3):213-8 Keywords Physical activity; endocrine system; Tanner Stage; youth ReSumoObjetivo: Avaliar as respostas hormonais ao teste de exercício em estágios incrementais (EX) até exaustão. Sujeitos e métodos: Foram examinados adolescentes com 16 anos de idade e índice Tanner 4 (TS4) e com 17 anos de idade e índice Tanner Stage 5 (TS5) (n = 6), e adultos com 21 ± 1 anos de idade. (X ± SD) (n = 4), estes últimos compondo o grupo controle. As amostras de sangue foram retiradas no repouso e ao final de cada estágio EX. Resultados: Os principais efeitos observados no EX ocorreram no cortisol (p < 0,01, aumentou com a elevação do estágio EX) e no grupo de testosterona (p < 0,01; TS4 < TS5, adultos). Houve efeito de interação entre grupos e por estágio de EX no grupo de hormônio de crescimento (p < 0,05). O hormônio de crescimento aumentou em todos os grupos em resposta ao EX, no entanto, a magnitude dos aumentos observados foi significativamente menor em TS5 e nos adultos do que em TS4. Conclusões: As diferenças verificadas nas respostas dos grupos de testosterona e hormônio de crescimento em TS4 em relação ao TS5 e adultos refletem os diferentes níveis de maturação do sistema endócrino entre os estágios do índice de Tanner. Os adolescentes no TS5 se assimilam mais aos jovens adultos do que aos adolescentes TS4, quanto a suas respostas hormonais ao EX.Arq Bras Endocrinol Metab. 2011;55(3):213-8 Descritores Atividade física; sistema endócrino; Etapa Tanner; jovem

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Participants experienced greater increases in cardiorespiratory and muscular fitness and physical function when PRIME training was initiated before a combined AT + RT program. This novel exercise approach may be advantageous to individuals with other chronic disease conditions characterized by low functional capacity.