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Purpose: The nadir pressure responses to cardiac cycles absent of muscle sympathetic nerve activity (MSNA) bursts (or non-bursts) are typically reported in studies quantifying sympathetic transduction, but the information gained by studying non-bursts is unclear. We tested the hypothesis that longer sequences of non-bursts (≥8 cardiac cycles) would be associated with a greater nadir diastolic blood pressure (DBP) and that better popliteal artery function would be associated with an augmented reduction in DBP., Methods: Resting beat-by-beat DBP (via finger photoplethysmography) and common peroneal nerve MSNA (via microneurography) were recorded in 39 healthy, adults (age 23.4 ± 5.3 years; 19 females). For each cardiac cycle absent of MSNA bursts, the mean nadir DBP (ΔDBP) during the 12 cardiac cycles following were determined, and separate analyses were conducted for ≥8 or < 8 cardiac cycle sequences. Popliteal artery endothelial-dependent (via flow-mediated dilation; FMD) and endothelial-independent vasodilation (via nitroglycerin-mediated dilation; NMD) were determined., Results: The nadir DBP responses to sequences ≥8 cardiac cycles were larger (-1.40 ± 1.27 mmHg) than sequences <8 (-0.38 ± 0.46 mmHg; p < 0.001). In adjusting for sex and burst frequency (14 ± 8 bursts/min), larger absolute or relative FMD (p < 0.01), but not NMD (p > 0.53) was associated with an augmented nadir DBP. This overall DBP-FMD relationship was similar in sequences ≥8 (p = 0.04-0.05), but not <8 (p > 0.72)., Conclusion: The DBP responses to non-bursts, particularly longer sequences, were inversely associated with popliteal endothelial function, but not vascular smooth muscle sensitivity. This study provides insight into the information gained by quantifying the DBP responses to cardiac cycles absent of MSNA., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Single bouts of prolonged bent-legged sitting attenuate popliteal endothelial-dependent vasodilation (as assessed via flow-mediated dilation [FMD]), which is partially attributed to arterial 'kinking'. However, the impact of knee-flexion angle on sitting-induced popliteal FMD is unknown. The objective of this study was to perform separate laboratory and free-living studies to test the hypotheses that: (1) popliteal FMD impairments would be graded between knee flexions at 90° (bent-legged sitting) > 45° > 0° (straight-legged sitting) following a 3-hour bout of sitting; and (2) more habitual time spent bent-legged sitting (< 45°) would be associated with lower FMD., Methods: The laboratory study included eight young, healthy adults (24 ± 2 years; four women) who underwent two sitting bouts over 2 days with one leg positioned at a knee-flexion angle of 0° or 90° and the opposite leg at 45° knee flexion. Popliteal FMD was assessed at pre- and postsitting timepoints., Results: Sitting-induced reductions in FMD were similar between all knee-flexion angles (all, p > 0.674). The free-living study included 35 young, healthy adults (23 ± 3 years; 16 women) who wore three activPAL monitors (torso, thigh, shin) to determine detailed sedentary postures. Time spent sedentary (624 ± 127 min/day), straight-legged sitting (112 ± 98 min/day), and bent-legged sitting (442 ± 106 min/day) were not related to relative FMD (5.3 ± 1.8%; all, p > 0.240)., Conclusion: These findings suggest that knee-flexion angle-mediated arterial 'kinking' during sitting is not a major contributor toward sitting-induced popliteal endothelial-dependent vasodilatory dysfunction., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Acute, laboratory-based bouts of prolonged sitting attenuate lower-limb arterial endothelial-dependent vasodilation. However, the impact of habitual sedentary patterns on popliteal artery endothelial health is unclear. We tested the hypothesis that greater habitual total sedentary time, more time spent in prolonged sedentary bouts, and fewer sedentary breaks would be associated with worse popliteal flow-mediated dilation (FMD) responses., Methods: This cross-sectional study used 98 healthy participants (19-77 years, 53 females) that wore an activPAL monitor on the thigh for 6.4 ± 0.8 days to objectively measure sedentary activity and completed a popliteal ultrasound assessment to determine FMD. Both relative (%baseline diameter) and absolute (mm) FMD were calculated. Using bivariate correlation and multiple regression analyses, we examined if there were relationships between sedentary outcomes and FMD while statistically controlling for any potential confounders., Results: In the multiple regression model, age ( p = 0.006, β = -0.030, 95% CI = -0.051, -0.009) and total time in sedentary bouts > 1 hour ( p = 0.031, β = -0.005, 95% CI = -0.009, -0.001) were independent predictors of relative FMD. Age (β = -0.002, 95% CI = -0.003, -0.001), mean blood flow (β = 0.013, 95% CI = 0.002, 0.024), moderate-intensity physical activity (β = 155.9E -5 , 95% CI = 22.4E -5 , 289.4E -5 ), sedentary breaks (β = 0.036, 95% CI = 0.007, 0.066), and total time spent in sedentary bouts > 1 hour (β = -25.02E -5 , 95% CI = -47.67E -5 , -2.378E -5 ) were predictors of absolute FMD (all, p < 0.047). All independent outcomes remained significant after partially controlling for all other predictor variables (all, p < 0.031)., Conclusions: Habitual prolonged sedentary bouts and sedentary breaks, but not total sedentary time, were predictors of popliteal endothelial-dependent vasodilatory function. The patterns by which sedentary time is accumulated may be more important than the total sedentary time on lower-limb arterial health.

Purpose: Acute prolonged bouts of sitting reduce popliteal artery blood flow and flow-mediated dilation (FMD). Individuals with higher aerobic fitness have enhanced popliteal FMD. Conflicting evidence regarding whether more aerobically fit individuals are protected from the negative impacts of sitting on popliteal endothelial function in male-dominated studies have been reported. We further explored the relationship between aerobic fitness and sitting-induced impairments in popliteal blood flow and FMD in a more sex-balanced cohort., Methods: Relative peak oxygen consumption (V̇O 2 peak) was assessed using a cycling-based incremental test in 21 healthy adults (eight males; 23 ± 2 years; 23.9 ± 2.9 kg/m 2 ). Popliteal blood flow and relative FMD (%) were measured via duplex ultrasonography before and after 3 h of uninterrupted sitting. Pearson correlations were performed separately between V̇O 2 peak versus pre-sitting and sitting-induced reductions in popliteal outcomes., Results: Aerobic fitness (41.0 ± 9.7 ml/kg/min) was positively correlated with pre-sitting popliteal blood flow (65 ± 23 mL/min; R = 0.59, P = 0.005) and relative FMD (4.2 ± 1.5%; R = 0.49, P = 0.03). As expected, sitting reduced resting blood flow (19 ± 11 mL/min) and FMD (1.9 ± 0.7%) (both, P < 0.001). V̇O 2 peak was inversely related to sitting-induced declines in blood flow (Δ-46 ± 23 mL/min; R = - 0.71, P < 0.001) and FMD (Δ-2.4 ± 1.5%; R = - 0.51, P = 0.02)., Conclusions: Although higher aerobic fitness was associated with more favorable popliteal endothelial-dependent vasodilator responses, it also corresponded with larger sitting-induced impairments in FMD. This suggests that being more aerobically fit does not protect against sitting-induced vascular endothelial dysfunction. As such, all young adults should minimize habitual prolonged sedentary bouts, regardless of their aerobic fitness level., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In the brachial artery, conflicting evidence exists regarding the relationship between the low-flow-mediated constriction (L-FMC) and subsequent flow-mediated dilation (FMD) responses, which may confound interpretation of the latter. The popliteal artery is a common site for atherosclerotic development, which is preceded by endothelial dysfunction. We aimed to determine whether the magnitude of popliteal L-FMC impacted FMD responses, which is currently unknown. L-FMC and FMD were assessed in the popliteal artery via high-resolution duplex ultrasonography and quantified as the percent change in diameter (from baseline) during ischaemia and in response to hyperaemia, respectively. Using partial correlations and multiple regression analyses, we evaluated the association between popliteal L-FMC on FMD in 110 healthy participants (60 females; 42 ± 22 [19-77] years). All variables univariately associated (p < 0.05) with popliteal relative FMD (relative L-FMC, log-SR AUC , age, systolic blood pressure, diastolic blood pressure, resting shear rate) were inputted into a model that explained 35% of the variance. The reactive hyperaemia stimulus (log-SR AUC : β = 1.10) and relative L-FMC (β = -0.39) were the only independent predictors of FMD (both, p < 0.01). Relative L-FMC was negatively correlated to relative FMD, after controlling for the significant univariate predictor variables listed above (R = -0.30; p = 0.002). An augmented (ie healthier) L-FMC response was linked with a larger FMD response as determined by the independent inverse association observed between these shear-stress-mediated measures of vasoreactivity., (© 2021 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.)

Lower-limb arteries, such as the popliteal artery, are a common site of atherosclerosis. These arteries are habitually exposed to large fluctuations in blood flow during physical and sedentary activities. Low-flow-mediated constriction (L-FMC) and flow-mediated dilation (FMD) provide indices of endothelial-dependent vasoconstriction and vasodilation, respectively. Age and sex both impact upper-limb FMD. However, it is unclear whether these factors also influence popliteal endothelial-dependent function. Popliteal endothelial function was compared between younger and older males and females (n=14 per group) matched for age- and sex-specific relative aerobic fitness levels (each group's normative percentile: ~45%). Nitroglycerin-mediated dilation (NMD) was also assessed as a measure of endothelial-independent vasodilation. Ageing reduced relative popliteal FMD in both males (older: 4.3±1.8% versus younger 5.7±1.9%) and females (older: 2.9±1.8% versus younger: 6.1±1.6%, both: P<0.046). FMD was also lower in older females versus older males (P=0.04). Popliteal NMD findings followed the same pattern as FMD. Compared to younger adults, relative L-FMC responses were blunted among older males (older: -1.2±1.1% versus younger: -2.2±1.0%) and females (older: -1.0±1.2% versus younger: -2.1±1.3%, both P<0.03) with no sex-differences observed in either age group (all, P>0.60). The adverse age- and sex-related (older adults only) declines in popliteal FMD were mediated, in part, by reduced vascular smooth muscle sensitivity to nitric oxide. Endothelial-dependent vasoconstriction was also attenuated with age, but unaffected by sex. Despite similar normative aerobic fitness percentiles (~45%), older adults exhibited attenuated popliteal endothelial function than their younger counterparts. This was particularly evident in older females who exhibited the lowest endothelial-dependent vasodilatory responses., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Uninterrupted sitting can impair popliteal flow-mediated dilation (FMD) responses in young, premenopausal females when endogenous or exogenous estrogen levels are low. However, it is unknown whether sitting-induced FMD responses are altered when estrogen levels are elevated in females who naturally menstruate (NAT) or those using combined, monophasic oral contraceptive pills (OCP). This study tested the hypothesis that the decline in popliteal FMD following an acute bout of prolonged sitting would be attenuated during the later versus earlier phases of a natural menstrual or OCP cycle. Popliteal FMD was measured before and after 3 h of sitting in NAT females ( n = 9; 23 ± 3 yr) and OCP females ( n = 9; 23 ± 3 yr) during both of their respective phases. At pre-sit, relative FMD was greater in the later phase versus earlier phase in NAT (4.6 ± 1.6% to 5.8 ± 1.5%; P = 0.002) but not between pill phases among OCP (4.4 ± 1.2% to 4.8 ± 1.6%; P = 0.32). Both groups exhibited similar prolonged sitting-induced impairments in popliteal FMD (pre- to post-sitting time: P < 0.001; group ΔFMD: P = 0.66; phase ΔFMD: P = 0.42; interaction ΔFMD: P = 0.72) regardless of menstrual cycle phase (earlier: -2.5 ± 1.5%; later: -2.4 ± 1.0%) or pill phase (inactive pill: -2.4 ± 1.4%; active pill: -2.1 ± 1.1%). Our findings demonstrate that lower-limb arterial endothelial-dependent vasodilatory function was enhanced in the later versus earlier menstrual phase among NAT but unaffected by combined, monophasic pill phases in OCP. Furthermore, healthy, young females exhibited pronounced negative lower-limb vascular effects in response to prolonged sitting regardless of whether they were in the earlier or later phases of a natural menstrual or contraceptive pill cycle. NEW & NOTEWORTHY We compared changes in popliteal artery endothelial function to a 3-h bout of sitting in females across their natural menstrual or oral contraceptive pill cycles. Pre-sitting endothelial-dependent vasodilation was greater in females who naturally menstruate during the later versus earlier phase but unchanged among contraceptive pill phases. Neither menstrual nor oral contraceptive pill phases attenuated the robust decline in conduit artery health following an acute period of uninterrupted sitting in young females.

An acute bout of prolonged sitting (PS) impairs the popliteal artery flow-mediated dilation (FMD) response. Despite equivocal reductions in mean shear rate, young women demonstrate an attenuated decline in popliteal FMD versus young men. However, it is uncertain whether popliteal endothelial-dependent vasoconstrictor responses [low-flow-mediated constriction (L-FMC)] are similarly affected by PS and/or whether sex differences exist. We tested the hypothesis that women would have attenuated reductions in both popliteal FMD and L-FMC responses following an acute bout of PS. Popliteal FMD and L-FMC responses were assessed via duplex ultrasonography before and after a 3-h bout of PS. These responses were then compared between 10 men (24 ± 2 yr) and 10 women (23 ± 2 yr) with similar ( P > 0.13) levels of objectively measured habitual physical activity (via PiezoRx) and sedentary time (via activPAL). At baseline, men and women exhibited similar ( P > 0.46) popliteal FMD (4.8 ± 1.2 vs. 4.5 ± 0.6%) and L-FMC (-1.7 ± 1.0 vs. -1.9 ± 0.9%) responses. Both sexes experienced identical (group: P > 0.76; time: P < 0.001) PS-induced impairments in popliteal FMD (-2.8 ± 1.4 vs. -2.6 ± 0.9%) and L-FMC (1.3 ± 0.7% vs. 1.4 ± 0.7%). In young adults, sex did not influence the negative PS-induced FMD, L-FMC, or microvascular responses in the lower limb. As such, our findings suggest that young men and women are similarly susceptible to the acute negative vascular effects of PS. Future studies should extend these findings to older, less physically active adults and/or patients with vascular disease. NEW & NOTEWORTHY We compared changes in popliteal artery endothelial function to a single 3-h bout of sitting between young men and women. Both groups exhibited similar endothelial-dependent vasodilation (i.e., flow-mediated dilation) and endothelial-dependent vasoconstrictor responses (i.e., low-flow-mediated constriction) at baseline and equivocal impairments in these measures of endothelial function following prolonged sitting. These findings demonstrate that acute impairments in conduit artery endothelial health associated with uninterrupted sitting are not influenced by sex in young, healthy adults.

We previously observed that brachial artery (BA) low-flow-mediated constriction (L-FMC) is inversely related to aerobic fitness (i.e., V̇o 2peak ) in older adults (OA). However, it is unclear if an L-FMC response is elicited in the popliteal artery (POP) or if a similar inverse relationship with aerobic fitness exists. Considering that the POP experiences larger shear stress fluctuations during sedentary behaviors and traditional lower limb modes of aerobic exercise, we tested the hypotheses that 1 ) heterogeneous L-FMC responses exist between the BA versus POP of OA, and 2 ) that aerobic fitness will be inversely related to POP L-FMC. L-FMC was assessed in 47 healthy OA (30 women, 67 ± 5 yr) using duplex ultrasonography and quantified as the percent decrease in diameter (from baseline) during the last 30 s of a 5-min distal cuff occlusion period. When allometrically scaled to baseline diameter, the BA exhibited a greater L-FMC response than the POP (-1.3 ± 1.6 vs. -0.4 ± 1.6%; P = 0.03). Furthermore, L-FMC responses in the BA and POP were not correlated ( r  = 0.22; P = 0.14). V̇o 2peak was strongly correlated to POP L-FMC ( r  = -0.73; P < 0.001). The heterogeneous BA versus POP L-FMC data indicate that upper limb L-FMC responses do not represent a systemic measure of endothelial-dependent vasoconstrictor capacity in OA. The strong association between V̇o 2peak and POP L-FMC suggests that localized shear stress patterns, perhaps induced by lower limb dominant modes of aerobic exercise, may result in greater vasoconstrictor responsiveness in healthy OA. NEW & NOTEWORTHY We compared low-flow-mediated constriction responses between the brachial and popliteal arteries of healthy older adults. Vasoconstrictor responses were not correlated between arteries. A strong relationship between aerobic fitness and low-flow-mediated vasoconstriction was observed in the popliteal artery. These findings suggest that brachial vasoconstrictor responsiveness is not reflective of the popliteal artery, which is exposed to larger shear stress fluctuations during bouts of sedentary behavior and traditional lower limb modes of exercise.

Canadian physical activity guidelines recommend older adults accumulate 150 min of weekly moderate to vigorous physical activity (MVPA). Older adults who are insufficiently active may have reduced blood vessel health and an increased risk of cardiovascular disease. We tested this hypothesis in 11 older adults who did (7 female; age, 65 ± 5 years; MVPA, = 239 ± 81 min/week) and 10 older adults who did not (7 female; age, 68 ± 9 years; MVPA, 95 ± 33 min/week) meet MVPA guidelines. Flow-mediated dilation (FMD) in the brachial (BA) and popliteal (POP) arteries, as well as nitroglycerin-mediated dilation (NMD; endothelial-independent dilation) in the POP were assessed via ultrasonography. Aerobic fitness (peak oxygen uptake) was determined using a graded, maximal cycle ergometry test via indirect calorimetry. MVPA and sedentary time were assessed over 5 days using the PiezoRx and activPAL, respectively. There were no differences in peak oxygen uptake (26 ± 10 vs. 22 ± 10 mL O 2 /(kg·min); p = 0.26) or sedentary time (512 ± 64 vs. 517 ± 76 min/day; p = 0.87) between groups; however, those who achieved the MVPA guidelines had a higher BA-FMD (5.1% ± 1.3% vs. 3.6% ± 1.7%; p = 0.03), POP-FMD (2.6% ± 1.1% vs. 1.3% ± 0.8%; p = 0.006), and POP-NMD (5.1% ± 1.7% vs. 3.3% ± 2.1%; p = 0.04). In the pooled sample, MVPA was moderately correlated to both BA-FMD (r = 0.53; p = 0.01) and POP-NMD (r = 0.59; p = 0.005), and strongly correlated to POP-FMD (r = 0.85; p < 0.001). Collectively, our results provide supporting evidence that meeting MVPA guidelines is associated with better vascular function and may reduce the risk of developing cardiovascular disease in older adults. Furthermore, these data suggest that weekly MVPA time may have a greater impact on blood vessel function than aerobic fitness and weekly sedentary time.