A High Activity Level Is Required for Augmented Muscle Capillarization in Older Women.

PURPOSE: This study aimed to evaluate the influence of lifelong regular physical activity on skeletal muscle capillarization in women. METHODS: Postmenopausal women, 61±4 yr old, were divided according to self-reported physical activity level over the past 20 yrs: sedentary (SED; n = 14), moderately active (MOD; n = 12), and very active (VERY; n = 15). Leg blood flow (LBF) was determined by ultrasound Doppler, and blood samples were drawn from the femoral artery and vein for calculation of leg oxygen uptake (LVO2) at rest and during one-legged knee extensor exercise. A skeletal muscle biopsy was obtained from the vastus lateralis and analyzed for capillarization and vascular endothelial growth factor (VEGF) and mitochondrial OXPHOS proteins. Platelets were isolated from venous blood and analyzed for VEGF content and effect on endothelial cell proliferation. RESULTS: The exercise-induced rise in LBF and LVO2 was faster (P = 0.008) in VERY compared with SED and MOD. Steady-state LBF and LVO2 were lower (P < 0.04) in MOD and VERY compared with SED. Capillary-fiber ratio and capillary density were greater (P < 0.03) in VERY (1.65 ± 0.48 and 409.3 ± 57.5) compared with MOD (1.30 ± 0.19 and 365.0 ± 40.2) and SED (1.30 ± 0.30 and 356.2 ± 66.3). Skeletal muscle VEGF and OXPHOS complexes I, II, and V were ~1.6-fold and ~1.25-fold (P < 0.01) higher, respectively, in VERY compared with SED. Platelets from all groups induced an approximately nine-fold (P < 0.001) increase in endothelial cell proliferation. CONCLUSION: A very active lifestyle is associated with superior skeletal muscle exercise hemodynamics and greater potential for oxygen extraction concurrent with a higher skeletal muscle capillarization and mitochondrial capacity.

The Impact of Lower Limb Immobilization and Rehabilitation on Angiogenic Proteins and Capillarization in Skeletal Muscle.

PURPOSE: Skeletal muscle vascularization is important for tissue regeneration after injury and immobilization. We examined whether complete immobilization influences capillarization and oxygen delivery to the muscle and assessed the efficacy of rehabilitation by aerobic exercise training. METHODS: Young healthy males had one leg immobilized for 14 d and subsequently completed 4 wk of intense aerobic exercise training. Biopsies were obtained from musculus vastus lateralis, and arteriovenous blood sampling for assessment of oxygen extraction and leg blood flow during exercise was done before and after immobilization and training. Muscle capillarization, muscle and platelet content of vascular endothelial growth factor (VEGF), and muscle thrombospondin-1 were determined. RESULTS: Immobilization did not have a significant impact on capillary per fiber ratio or capillary density. The content of VEGF protein in muscle samples was reduced by 36% (P = 0.024), and VEGF to thrombospondin-1 ratio was 94% lower (P = 0.046). The subsequent 4-wk training period increased the muscle VEGF content and normalized the muscle VEGF to thrombospondin-1 ratio but did not influence capillarization. Platelet VEGF content followed the trend of muscle VEGF. At the functional level, oxygen extraction, blood flow, and oxygen delivery at rest and during submaximal exercise were not affected by immobilization or training. CONCLUSIONS: The results demonstrate that just 2 wk of leg immobilization leads to a strongly reduced angiogenic potential as evidenced by reduced muscle and platelet VEGF content and a reduced muscle VEGF to thrombospondin-1 ratio. Moreover, a subsequent period of intensive aerobic exercise training fails to increase capillarization in the previously immobilized leg, possibly because of the angiostatic condition caused by immobilization.

Can exercise training enhance the repeated remote ischaemic preconditioning stimulus on peripheral and cerebrovascular function in high-risk individuals?

BACKGROUND: Repeated exposure to remote ischaemic preconditioning (rIPC; short bouts of non-lethal ischaemia) enhances peripheral vascular function within 1 week; whereas, longer periods of rIPC (~ 1 year) may improve cerebral perfusion. Increasing the 'dose' of rIPC may lead to superior effects. Given the similarities between exercise and rIPC, we examined whether adding exercise to the rIPC stimulus leads to greater adaptation in systemic vascular function. METHODS: Nineteen individuals with increased risk for cardiovascular disease (CVD) were randomly allocated to either 8 weeks of rIPC (n = 9) or 8 weeks of rIPC + exercise (rIPC + Ex) (n = 10). rIPC was applied three times per week in both conditions, and exercise consisted of 50 min (70% heart rate max) of cycling 3 times per week. Peripheral endothelial function was assessed using flow-mediated dilation (FMD) before and after ischaemia-reperfusion (IR). Cerebrovascular function was assessed by dynamic cerebral autoregulation (dCA) and cerebrovascular reactivity (CVR), and cardio-respiratory fitness (VO2peak) using a maximal aerobic capacity test. RESULTS: FMD% increased by 1.6% (95% CI, 0.4, 2.8) following rIPC + Ex and by 0.3% (- 1.1, 1.5) in the only rIPC but this did not reach statistical significance (P = 0.65). Neither intervention evoked a change in dCA or in CVR (P > 0.05). VO2peak increased by 2.8 ml/kg/min (1.7, 3.9) following the rIPC + Ex and by 0.1 ml/kg/min (- 1.0, 1.4) following the rIPC only intervention (P = 0.69). CONCLUSION: Combining exercise with rIPC across an 8-week intervention does not lead to superior effects in cerebrovascular and peripheral vascular function compared to a repeated rIPC intervention in individuals at risk of CVD.

Aerobic High-Intensity Exercise Training Improves Cardiovascular Health in Older Post-menopausal Women.

The aim of this study was to determine the effect of a period of aerobic high intensity training on central- and peripheral cardiovascular parameters in older post-menopausal women. Eleven healthy post-menopausal (>10 years after menopause) women (mean age: 64 years; BMI: 25.3 kg m-2) completed an 8-week period of supervised, high intensity cycle training, with sessions conducted three times per week. Before and after the training period maximal oxygen uptake, body composition, popliteal artery flow mediated dilation, exercise hyperemia, arterial blood pressure, and plasma lipids were assessed. In addition, levels of estrogen related receptor α (ERRα) and vasodilator enzymes were determined in muscle biopsy samples. Training induced an 18% increase (P < 0.001) in maximal oxygen uptake. Plasma High-density lipoprotein (HDL) was higher (P < 0.05) after than before the training period. Fat mass was reduced (4.9%; P < 0.01), whereas lean body mass was unaltered. Mean arterial blood pressure was unchanged (91 vs. 88 mmHg; P = 0.058) with training. Training did not induce a change in popliteal flow mediated dilation. Exercise hyperemia at submaximal exercise was lower (P < 0.01; 11 and 4.6% at 10 and 16 W, respectively) after compared to before training. Muscle ERRα (~1.7-fold; P < 0.01) and eNOS (~1.4-fold; P < 0.05) were higher after the training intervention. The current study demonstrates that, in older post-menopausal women, a period of aerobic high intensity training effectively increases maximal oxygen uptake and improves the cardiovascular health profile, without a parallel improvement in conduit artery function.

Brachial and Cerebrovascular Functions Are Enhanced in Postmenopausal Women after Ingestion of Chocolate with a High Concentration of Cocoa.

Background: Cocoa contains polyphenols that are thought to be beneficial for vascular health.Objective: We assessed the impact of chocolate containing distinct concentrations of cocoa on cerebrovascular function and cognition.Methods: Using a counterbalanced within-subject design, we compared the acute impact of consumption of energy-matched chocolate containing 80%, 35%, and 0% single-origin cacao on vascular endothelial function, cognition, and cerebrovascular function in 12 healthy postmenopausal women (mean ± SD age: 57.3 ± 5.3 y). Participants attended a familiarization session, followed by 3 experimental trials, each separated by 1 wk. Outcome measures included cerebral blood flow velocity (CBFv) responses, recorded before and during completion of a computerized cognitive assessment battery (CogState); brachial artery flow-mediated dilation (FMD); and hemodynamic responses (heart rate and blood pressure).Results: When CBFv data before and after chocolate intake were compared between conditions through the use of 2-factor ANOVA, an interaction effect (P = 0.003) and main effects for chocolate (P = 0.043) and time (P = 0.001) were evident. Post hoc analysis revealed that both milk chocolate (MC; 35% cocoa; P = 0.02) and dark chocolate (DC; 80% cocoa; P = 0.003) induced significantly lower cerebral blood flow responses during the cognitive tasks, after normalizing for changes in arterial pressure. DC consumption also increased brachial FMD compared with the baseline value before chocolate consumption (P = 0.002), whereas MC and white chocolate (0% cocoa) caused no change (P-interaction between conditions = 0.034).Conclusions: Consumption of chocolate containing high concentrations of cocoa enhanced vascular endothelial function, which was reflected by improvements in FMD. Cognitive function outcomes did not differ between conditions; however, cerebral blood flow responses during these cognitive tasks were lower in those consuming MC and DC. These findings suggest that chocolate containing high concentrations of cocoa may modify the relation between cerebral metabolism and blood flow responses in postmenopausal women. This trial was registered at www.ANZCTR.orgau as ACTRN12616000990426.

Differential impact of water immersion on arterial blood flow and shear stress in the carotid and brachial arteries of humans.

Arterial shear stress is a potent stimulus to vascular adaptation in humans. Typically, increases in retrograde shear have been found to acutely impair vascular function while increases in antegrade shear enhance function. We hypothesized that blood flow and shear stress through the brachial and carotid arteries would change in a similar manner in response to water immersion, an intervention which modifies hemodynamics. Nine healthy young male subjects were recruited to undergo controlled water immersion in a standing upright position to the level of the right atrium in 30°C water. Diameters were continuously and simultaneously recorded in the brachial and common carotid arteries along with mean arterial pressure (MAP), cardiac output (CO), and heart rate before, during, and after 10 min of immersion. MAP and CO increased during water immersion (baseline vs. 8-10 min; 80 ± 9 vs. 91 ± 12 mmHg; and 4.8 ± 0.7 vs. 5.1 ± 0.6 L/min, P < 0.01 and P < 0.05, respectively). We observed a differential regulation of flow and shear stress patterns in the brachial and carotid arteries in response to water immersion; brachial conductance decreased markedly in response to immersion (1.25 ± 0.56 vs. 0.57 ± 0.30 mL.min/mmHg, P < 0.05), whereas it was unaltered in the carotid artery (5.82 ± 2.14 vs. 5.60 ± 1.59). Our findings indicate that adaptations to systemic stimuli and arterial adaptation may be vessel bed specific in humans, highlighting the need to assess multiple vascular sites in future studies.