We have previously shown that local heating or leg fidgeting can prevent prolonged sitting-induced leg endothelial dysfunction. However, whether physical activity prevents subsequent sitting-induced ...leg endothelial dysfunction remains unknown. Herein, we tested the hypothesis that sitting-induced leg endothelial dysfunction would be prevented by prior exercise. We also examined if, in the absence of exercise, standing is an effective alternative strategy to sitting for conserving leg endothelial function. Fifteen young healthy subjects completed three randomized experimental trials: (1) sitting without prior exercise; (2) sitting with prior exercise; and (3) standing without prior exercise. Following baseline popliteal artery flow-mediated dilation (FMD) measurements, subjects maintained a supine position for 45 min in the sitting and standing trials, without prior exercise, or performed 45 min of leg cycling before sitting (i.e. sitting with prior exercise trial). Thereafter, subjects were positioned into a seated or standing position, according to the trial, for 3 h. Popliteal artery FMD measures were then repeated. Three hours of sitting without prior exercise caused a significant impairment in popliteal artery FMD (baseline: 3.8±0.5%, post-sitting: 1.5±0.5%,
<0.05), which was prevented when sitting was preceded by a bout of cycling exercise (baseline: 3.8±0.5%, post-sitting: 3.6±0.7%,
>0.05). Three hours of standing did not significantly alter popliteal artery FMD (baseline: 4.1±0.4%, post-standing: 4.3±0.4%,
>0.05). In conclusion, prolonged sitting-induced leg endothelial dysfunction can be prevented by prior aerobic exercise. In addition, in the absence of exercise, standing represents an effective substitute to sitting for preserving leg conduit artery endothelial function.
New Findings
What is the central question of this study?
The prevalence of sedentary behaviour in the workplace and increased daily sitting time have been associated with the development of ...cardiovascular disease; however, studies investigating the impact of sitting on vascular function remain limited.
What is the main finding and its importance?
We demonstrate that there is a marked vulnerability of the vasculature in the lower and upper limbs to prolonged sitting and highlight the importance of physical activity in restoring vascular function in a limb‐specific manner.
Sedentary behaviour in the workplace and increased daily sitting time are on the rise; however, studies investigating the impact of sitting on vascular function remain limited. Herein, we hypothesized that 6 h of uninterrupted sitting would impair limb micro‐ and macrovascular dilator function and that this impairment could be improved with a bout of walking. Resting blood flow, reactive hyperaemia to 5 min cuff occlusion (microvascular reactivity) and associated flow‐mediated dilatation (FMD; macrovascular reactivity) were assessed in popliteal and brachial arteries of young men at baseline (Pre Sit) and after 6 h of uninterrupted sitting (Post Sit). Measures were then repeated after a 10 min walk (∼1000 steps). Sitting resulted in a marked reduction of resting popliteal artery mean blood flow and mean shear rate (6 h mean shear rate, −52 ± 8 s−1 versus Pre Sit, P < 0.05). Interestingly, reductions were also found in the brachial artery (6 h mean shear rate, −169 ± 41 s−1 versus Pre Sit, P < 0.05). Likewise, after 6 h of sitting, cuff‐induced reactive hyperaemia was reduced in both the lower leg (−43 ± 7% versus Pre Sit, P < 0.05) and forearm (−31 ± 11% versus Pre Sit, P < 0.05). In contrast, popliteal but not brachial artery FMD was blunted with sitting. Notably, lower leg reactive hyperaemia and FMD were restored after walking. Collectively, these data suggest that prolonged sitting markedly reduces lower leg micro‐ and macrovascular dilator function, but these impairments can be fully normalized with a short bout of walking. In contrast, upper arm microvascular reactivity is selectively impaired with prolonged sitting, and walking does not influence this effect.
Prolonged sitting impairs endothelial function in the leg vasculature, and this impairment is thought to be largely mediated by a sustained reduction in blood flow-induced shear stress. Indeed, ...preventing the marked reduction of shear stress during sitting with local heating abolishes the impairment in popliteal artery endothelial function. Herein, we tested the hypothesis that sitting-induced reductions in shear stress and ensuing endothelial dysfunction would be prevented by periodic leg movement, or "fidgeting." In 11 young, healthy subjects, bilateral measurements of popliteal artery flow-mediated dilation (FMD) were performed before and after a 3-h sitting period during which one leg was subjected to intermittent fidgeting (1 min on/4 min off) while the contralateral leg remained still throughout and served as an internal control. Fidgeting produced a pronounced increase in popliteal artery blood flow and shear rate (prefidgeting, 33.7 ± 2.6 s(-1) to immediately postfidgeting, 222.7 ± 28.3 s(-1); mean ± SE; P < 0.001) that tapered off during the following 60 s. Fidgeting did not alter popliteal artery blood flow and shear rate of the contralateral leg, which was subjected to a reduction in blood flow and shear rate throughout the sitting period (presit, 71.7 ± 8.0 s(-1) to 3-h sit, 20.2 ± 2.9 s(-1); P < 0.001). Popliteal artery FMD was impaired after 3 h of sitting in the control leg (presit, 4.5 ± 0.3% to postsit: 1.6 ± 1.1%; P = 0.039) but improved in the fidgeting leg (presit, 3.7 ± 0.6% to postsit, 6.6 ± 1.2%; P = 0.014). Collectively, the present study provides evidence that prolonged sitting-induced leg endothelial dysfunction is preventable with small amounts of leg movement while sitting, likely through the intermittent increases in vascular shear stress.
We and others have recently reported that prolonged sitting impairs endothelial function in the leg vasculature; however, the mechanism(s) remain unknown. Herein, we tested the hypothesis that a ...sustained reduction in flow-induced shear stress is the underlying mechanism by which sitting induces leg endothelial dysfunction. Specifically, we examined whether preventing the reduction in shear stress during sitting would abolish the detrimental effects of sitting on popliteal artery endothelial function. In 10 young healthy men, bilateral measurements of popliteal artery flow-mediated dilation were performed before and after a 3-h sitting period during which one foot was submerged in 42°C water (i.e., heated) to increase blood flow and thus shear stress, whereas the contralateral leg remained dry and served as internal control (i.e., nonheated). During sitting, popliteal artery mean shear rate was reduced in the nonheated leg (pre-sit, 42.9 ± 4.5 s(-1); and 3-h sit, 23.6 ± 3.3 s(-1); P < 0.05) but not in the heated leg (pre-sit, 38.9 ± 3.4 s(-1); and 3-h sit, 63.9 ± 16.9 s(-1); P > 0.05). Popliteal artery flow-mediated dilation was impaired after 3 h of sitting in the nonheated leg (pre-sit, 7.1 ± 1.4% vs. post-sit, 2.8 ± 0.9%; P < 0.05) but not in the heated leg (pre-sit: 7.3 ± 1.5% vs. post-sit, 10.9 ± 1.8%; P > 0.05). Collectively, these data suggest that preventing the reduction of flow-induced shear stress during prolonged sitting with local heating abolishes the impairment in popliteal artery endothelial function. Thus these findings are consistent with the hypothesis that sitting-induced leg endothelial dysfunction is mediated by a reduction in shear stress.
Postprandial hyperglycaemia leads to a transient impairment in endothelial function; however, the mechanisms remain largely unknown. Previous work in cell culture models demonstrate that high glucose ...results in endoplasmic reticulum (ER) stress and, in animal studies, ER stress has been implicated as a cause of endothelial dysfunction. In the present study, we tested the hypothesis that acute oral administration of tauroursodeoxycholic acid (TUDCA, 1500 mg), a chemical chaperone known to alleviate ER stress, would prevent hyperglycaemia-induced endothelial dysfunction. In 12 young healthy subjects (seven men, five women), brachial artery flow-mediated dilation (FMD) was assessed at baseline, and at 60 and 120 min after an oral glucose challenge. Subjects were tested on two separate visits in a single-blind randomized cross-over design: after oral ingestion of TUDCA or placebo capsules. FMD was reduced from baseline during hyperglycaemia under the placebo condition (-32% at 60 min and -28% at 120 min post oral glucose load; P<0.05 from baseline) but not under the TUDCA condition (-4% at 60 min and +0.3% at 120 min post oral glucose load; P>0.05 from baseline). Postprandial plasma glucose and insulin were not altered by TUDCA ingestion. Plasma oxidative stress markers 3-nitrotyrosine and thiobarbituric acid reactive substance (TBARS) remained unaltered throughout the oral glucose challenge in both conditions. These results suggest that hyperglycaemia-induced endothelial dysfunction can be mitigated by oral administration of TUDCA, thus supporting the hypothesis that ER stress may contribute to endothelial dysfunction during postprandial hyperglycaemia.
Previous studies have reported exaggerated increases in arterial blood pressure during exercise in type 2 diabetes (T2D) patients. However, little is known regarding the underlying neural ...mechanism(s) involved. We hypothesized that T2D patients would exhibit an augmented muscle metaboreflex activation and this contributes to greater pressor and sympathetic responses during exercise. Mean arterial pressure (MAP), heart rate (HR), and muscle sympathetic nerve activity (MSNA) were measured in 16 patients with T2D (8 normotensive and 8 hypertensive) and 10 healthy controls. Graded isolation of the muscle metaboreflex was achieved by postexercise ischemia (PEI) following static handgrip performed at 30% and 40% maximal voluntary contraction (MVC). A cold pressor test (CPT) was also performed as a generalized sympathoexcitatory stimulus. Increases in MAP and MSNA during 30 and 40% MVC handgrip were augmented in T2D patients compared with controls (P < 0.05), and these differences were maintained during PEI (MAP: 30% MVC PEI: T2D, Δ16 ± 2 mmHg vs. controls, Δ8 ± 1 mmHg; 40% MVC PEI: T2D, Δ26 ± 3 mmHg vs. controls, Δ16 ± 2 mmHg, both P < 0.05). MAP and MSNA responses to handgrip and PEI were not different between normotensive and hypertensive T2D patients (P > 0.05). Interestingly, MSNA responses were also greater in T2D patients compared with controls during the CPT (P < 0.05). Collectively, these findings indicate that muscle metaboreflex activation is augmented in T2D patients and this contributes, in part, to augmented pressor and sympathetic responses to exercise in this patient group. Greater CPT responses suggest that a heightened central sympathetic reactivity may be involved.
Rapid-onset vasodilation (ROV) following single muscle contractions has been examined in the forearm of humans, but has not yet been characterized in the leg. Given known vascular differences between ...the arm and leg, we sought to characterize ROV following single muscle contractions in the leg. Sixteen healthy men performed random ordered single contractions at 5, 10, 20, 40, and 60% of their maximum voluntary contraction (MVC) using isometric knee extension made with the leg above and below heart level, and these were compared with single isometric contractions of the forearm (handgrip). Single thigh cuff compressions (300 mmHg) were utilized to estimate the mechanical contribution to leg ROV. Continuous blood flow was determined by duplex-Doppler ultrasound and blood pressure via finger photoplethysmography (Finometer). Single isometric knee extensor contractions produced intensity-dependent increases in peak leg vascular conductance that were significantly greater than the forearm in both the above- and below-heart level positions (e.g., above heart level: leg 20% MVC, +138 ± 28% vs. arm 20% MVC, +89 ± 17%; P < 0.05). Thigh cuff compressions also produced a significant hyperemic response, but these were brief and smaller in magnitude compared with single isometric contractions in the leg. Collectively, these data demonstrate the presence of a rapid and robust vasodilation to single muscle contractions in the leg that is largely independent of mechanical factors, thus establishing the leg as a viable model to study ROV in humans.
Despite greater blood pressure reactivity to acute cardiovascular stressors and a higher prevalence of hypertension in type 2 diabetes (T2D) patients, limited information is available regarding ...arterial baroreflex (ABR) control in T2D. We hypothesized that ABR control of muscle sympathetic nerve activity (MSNA) and heart rate (HR) are attenuated in T2D patients. Seventeen T2D patients (50 ± 2 yr; 31 ± 1 kg/m
), 9 weight-matched controls (WM-CON, 46 ± 2 yr; 32 ± 2 kg/m
) and 10 lean controls (Lean-CON, 49 ± 3 yr; 23 ± 1 kg/m
), underwent bolus infusions of sodium nitroprusside (100 μg) followed 60 s later by phenylephrine (150 μg) and weighted linear regression performed. No group differences in overall sympathetic baroreflex gain were observed (T2D: -2.5 ± 0.3 vs. WM-CON: -2.6 ± 0.2 vs. Lean-CON: -2.7 ± 0.4 arbitrary units·beat·mmHg
, P > 0.05) or in sympathetic baroreflex gain when derived separately during blood pressure (BP) falls (nitroprusside) and BP rises (phenylephrine). In contrast, overall cardiac baroreflex gain was reduced in T2D patients compared with Lean-CON (T2D: 8.2 ± 1.5 vs. Lean-CON: 15.6 ± 2.9 ms·mmHg
, P < 0.05) and also tended to be reduced in WM-CON (9.3 ± 1.9 ms·mmHg
) compared with Lean-CON (P = 0.059). Likewise, during BP rises, cardiac baroreflex gain was reduced in T2D patients and weight-matched controls compared with lean controls (P < 0.05), whereas no group differences were found during BP falls (P > 0.05). Sympathetic and cardiac ABR gains were comparable between normotensive and hypertensive T2D patients (P > 0.05). These findings suggest preserved ABR control of MSNA in T2D patients compared with both obese and lean age-matched counterparts, with a selective impairment in ABR HR control in T2D that may be related to obesity.
Physical inactivity is associated with disruptions in glucose metabolism and energy balance, whereas energy restriction may blunt these adverse manifestations. During hypocaloric feeding, ...higher-protein intake maintains lean mass which is an important component of metabolic health. This study determined whether mild energy restriction preserves glycemic control during physical inactivity and whether this preservation is more effectively achieved with a higher-protein diet.
Ten adults (24 ± 1 yr) consumed a control (64% carbohydrate, 20% fat, 16% protein) and higher-protein diet (50% carbohydrate, 20% fat, 30% protein) during two 10-d inactivity periods (>10,000 → ~5000 steps per day) in a randomized crossover design. Energy intake was decreased by ~400 kcal·d to account for reduced energy expenditure associated with inactivity. A subset of subjects (n = 5) completed 10 d of inactivity while consuming 35% excess of their basal energy requirements, which served as a positive control condition (overfeeding+inactivity).
Daily steps were decreased from 12,154 ± 308 to 4275 ± 269 steps per day (P < 0.05) which was accompanied by reduced V˙O2max (-1.8 ± 0.7 mL·kg·min, P < 0.05), independent of diet conditions. No disruptions in fasting or postprandial glucose, insulin, and nonesterified fatty acids in response to 75 g of oral glucose were observed after inactivity for both diet conditions (P > 0.05). Overfeeding+inactivity increased body weight, body fat, homeostasis model assessment of insulin resistance, and 2-h postprandial glucose and insulin concentrations (P < 0.05), despite no changes in lipid concentrations.
We show that independent of diet (normal vs higher-protein), mild energy restriction preserves metabolic function during short-term inactivity in healthy subjects. That is, metabolic deterioration with inactivity only manifests in the setting of energy surplus.
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