Key points: Passive leg movement is associated with a ∼3‐fold increase in blood flow to the leg, but the underlying mechanisms remain unknown. Passive leg movement increased venous levels of metabolites of nitric oxide (NO) in young subjects, whereas they remained unaltered in the muscle interstitial space. Inhibition of NO synthesis lowered the vasodilatory response to passive leg movement by ∼90%. The increase in leg blood flow was lower in elderly subjects compared to young subjects and leg blood flow did not increase when passive leg movement was performed by elderly with peripheral artery disease. The results suggest that the hyperaemia induced by passive leg movement is NO dependent. The hyperaemic response to passive leg movement and to ACh was also assessed in elderly subjects and patients with peripheral artery disease. Abstract  Passive leg movement is associated with a ∼3‐fold increase in blood flow to the leg but the underlying mechanisms remain unknown. The objective of the present study was to examine the role of nitric oxide (NO) for the hyperaemia observed during passive leg movement. Leg haemodynamics and metabolites of NO production (nitrite and nitrate; NOx) were measured in plasma and muscle interstitial fluid at rest and during passive leg movement with and without inhibition of NO formation in healthy young males. The hyperaemic response to passive leg movement and to ACh was also assessed in elderly subjects and patients with peripheral artery disease. Passive leg movement (60 r.p.m.) increased leg blood flow from 0.3 ± 0.1 to 0.9 ± 0.1 litre min⁻¹ at 20 s and 0.5 ± 0.1 litre min⁻¹ at 3 min (P < 0.05). Mean arterial pressure remained unchanged during the trial. When passive leg movement was performed during inhibition of NO formation (N^G‐mono‐methyl‐l‐arginine; 29–52 mg min⁻¹), leg blood flow and vascular conductance were increased after 20 s (P < 0.05) and then returned to baseline levels, despite an increase in arterial pressure (P < 0.05). Passive leg movement increased the femoral venous NOx levels from 35 ± 5 at baseline to 62 ± 11 μmol l⁻¹ during passive leg movement (P < 0.05), whereas muscle interstitial NOx levels remained unchanged. The hyperaemic response to passive leg movement were correlated with the vasodilatation induced by ACh (r²= 0.704, P < 0.001) and with age (r²= 0.612, P < 0.001). Leg blood flow did not increase during passive leg movement in individuals with peripheral arterial disease. These results suggest that the hypaeremia induced by passive leg movement is NO dependent and that the source of NO is likely to be the endothelium. Passive leg movement could therefore be used as a non‐invasive tool to evaluate NO dependent endothelial function of the lower limb.

Aging is often associated with reduced leg blood flow, increased arterial stiffness, and endothelial dysfunction, all of which are related to declining nitric oxide (NO) bioavailability. Flow mediated dilatation (FMD) and passive leg movement (PLM) hyperaemia are two techniques used to measure NO-dependent vascular function. We hypothesised that acute dietary nitrate (NO₃⁻) supplementation would improve NO bioavailability, leg FMD, and PLM hyperaemia. Fifteen healthy older men (69 ± 4 years) attended two experiment sessions and consumed either 140 mL of concentrated beetroot juice (800 mg NO₃⁻) or placebo (NO₃⁻-depleted beetroot juice) in a randomised, double blind, cross-over design study. Plasma nitrite (NO₂⁻) and NO₃⁻, blood pressure (BP), augmentation index (AIx75), pulse wave velocity (PWV), FMD of the superficial femoral artery, and PLM hyperaemia were measured immediately before and 2.5 h after consuming NO₃⁻ and placebo. Placebo had no effect but NO₃⁻ led to an 8.6-fold increase in plasma NO₂⁻, which was accompanied by an increase in FMD (NO₃⁻: +1.18 ± 0.94% vs. placebo: 0.23 ± 1.13%, p = 0.002), and a reduction in AIx75 (NO₃⁻: −8.7 ± 11.6% vs. placebo: −4.6 ± 5.5%, p = 0.027). PLM hyperaemia, BP, and PWV were unchanged during both trials. This study showed that a dose of dietary NO₃⁻ improved NO bioavailability and enhanced endothelial function as measured by femoral artery FMD. These findings provide insight into the specific central and peripheral vascular responses to dietary NO₃⁻ supplementation in older adults.

Intermittent claudication (IC) is the most commonly reported symptom of peripheral arterial disease (PAD). Impaired limb blood flow is a major casual factor of lower exercise tolerance in PAD but cannot entirely explain it. We hypothesized that IC is associated with structural changes of the capillary-mitochondria interface that could contribute to the reduction of exercise tolerance in IC patients. Capillary and mitochondrial morphometry were performed after light and transmission electron microscopy using vastus lateralis muscle biopsies of 14 IC patients and 10 age-matched controls, and peak power output (PPO) was determined for all participants using an incremental single-leg knee-extension protocol. Capillary density was lower (411 ± 90 mm⁻²vs. 506 ± 95 mm⁻²; P ≤ 0.05) in the biopsies of the IC patients than in those of the controls. The basement membrane (BM) around capillaries was thicker (543 ± 82 nm vs. 423 ± 97 nm; P ≤ 0.01) and the volume density of mitochondria was lower (3.51 ± 0.56% vs. 4.60 ± 0.74%; P ≤ 0.01) in the IC patients than the controls. In the IC patients, a higher proportion of capillaries appeared with collapsed slit-like lumen and/or swollen endothelium. PPO was lower (18.5 ± 9.9 W vs. 33.5 ± 9.4 W; P ≤ 0.01) in the IC patients than the controls. We suggest that several structural alterations in skeletal muscle, either collectively or separately, contribute to the reduction of exercise tolerance in IC patients.

Background: The benefits of exercise for patients with cancer are well-established, however, for patients with bone metastases, exercise as adjuvant therapy is underutilised due to concerns for safety, efficacy and other barriers such as the method of delivery. This scoping review explores these barriers by reviewing the results of clinical trials conducted on participants with bone metastases. Methods: A thorough literature search was undertaken using PubMed, Scopus, NIH Clinical Trials and Google Scholar databases. Articles that involved an exercise intervention and patients with bone metastases were included. Data were pooled, charted, analysed and reported according to PRISMA-ScR standards. Results: A total of 26 trials were reviewed with interventions that included aerobic and resistance training. Only three serious adverse events occurred, not likely related to bone metastases. Nine trials (34.6%) involved unsupervised exercise sessions. Remote exercise delivery had an average of 80.3% compliance, rivalling in-person and mixed supervision. The results of this review reaffirm that exercise helps improve functional capacity, muscle strength, lean mass and cardiovascular function, and is safe in patients with bone metastases irrespective of in-person or remote delivery. Conclusions: Exercise therapy, whether delivered in person or remotely, is safe and efficacious for patients with bone metastases.

Prostate cancer survivors treated with androgen deprivation therapy may be at increased risk of cardiovascular disease. Dietary recommendations for the prevention and/or management of cardiovascular disease for these individuals are lacking. This review synthesizes the evidence on the effect of dietary interventions on cardiometabolic biomarkers and cardiovascular disease risk in prostate cancer survivors receiving androgen deprivation therapy. A systematic review was conducted across PubMed, CINAHL, Embase, and Cochrane CENTRAL. Intervention or observational cohort studies evaluating diets, nutrients, or nutraceuticals with or without concurrent exercise interventions on cardiovascular disease, cardiovascular events, or cardiovascular disease biomarkers in those treated with androgen deprivation therapy were included. Confidence in the body of evidence was appraised using Grading of Recommendations, Assessment, Development and Evaluations. Twelve studies reported across fifteen papers were included. Interventions were heterogenous, with most studies including an exercise co-intervention (n = 8). Few significant findings for the effects of diet on cardiometabolic markers were likely due to weak methodology and sample sizes. Strongest evidence was for the effect of a healthy Western dietary pattern with exercise on improved blood pressure (Confidence: moderate). The healthy Western dietary pattern with exercise may improve high-density lipoprotein cholesterol (Confidence: Low) and flow-mediated dilation. Soy may improve total cholesterol (Confidence: Very low). A low-carbohydrate diet with physical activity may improve high-density lipoprotein cholesterol, incidence of metabolic syndrome, and Framingham cardiovascular disease risk score. Evidence of the effect of dietary interventions on cardiometabolic biomarkers and cardiovascular disease risk of prostate cancer survivors receiving androgen deprivation therapy is insufficient to inform practice. Well-designed dietary interventions aimed at improving cardiometabolic outcomes of this population are warranted to inform future dietary recommendations.