Low-flow-mediated Constriction Research Articles

Mechanistic, participant, and movement-related factors that contribute to low-flow-mediated constriction.

Endothelial function is commonly determined via the ultrasound-based flow-mediated dilation (FMD) technique which assesses arterial dilation in response to a hyperemia response following distal cuff occlusion. However, the low-flow-mediated constriction (L-FMC) response during cuff-induced ischemia is often overlooked. L-FMC provides unique information regarding endothelial function, but vascular researchers may be unclear on what this metric adds. Therefore, the objective of this review was to examine the mechanistic determinants and participant-level factors of L-FMC. Existing mechanistic studies have demonstrated that vasoreactivity to low flow may be mediated via non-nitric oxide vasodilators (i.e., endothelial hyperpolarizing factors and/or prostaglandins), inflammatory markers, and enhancement of vasoconstriction via endothelin-1. In general, participant-level factors such as aging and presence of cardiovascular conditions generally are associated with attenuated L-FMC responses. However, the influence of sex on L-FMC is unclear with divergent results between L-FMC in upper versus lower limb vessels. The ability of aerobic exercise to augment L-FMC (i.e., make more negative) is well supported, but there is a major gap in the literature concerning the mechanistic underpinnings of this observation. This review summarizes that while larger L-FMC responses are generally healthy, the impact of interventions to augment/attenuate L-FMC has not included mechanistic measures that would provide insight into non-nitric oxide-based endothelial function. Clarifications to terminology and areas of further inquiry as it relates to the specific pharmacological, individual-level factors, and lifestyle behaviors that impact L-FMC are highlighted. A greater integration of mechanistic work alongside applied lifestyle interventions is required to better understand endothelial cell function to reductions in local blood flow.

Brachial Artery Low-Flow-Mediated Constriction (L-FMC) Is Augmented In Older Women

Brachial Artery Low-Flow-Mediated Constriction (L-FMC) Is Augmented In Older Women

Impact of acute dynamic exercise and arterial shear rate modification on radial artery low-flow mediated constriction in young men

PurposeLeg cycling exercise acutely augments radial artery low-flow mediated constriction (L-FMC). Herein, we sought to determine whether this is associated with exercise-induced changes in arterial shear rate (SR).MethodsTen healthy and recreationally active young men (23 ± 2 years) participated in 30 min of incremental leg cycling exercise (50, 100, 150 Watts). Trials were repeated with (Exercise + WC) and without (Exercise) the use of a wrist cuff (75 mmHg) placed distal to the radial artery to increase local retrograde SR while reducing mean and anterograde SR. Radial artery characteristics were measured throughout the trial, and L-FMC and flow mediated dilatation (FMD) were assessed before and acutely (~ 10 min) after leg cycling.ResultsExercise increased radial artery mean and anterograde SR, along with radial artery diameter, velocity, blood flow and conductance (P < 0.05). Exercise + WC attenuated the exercise-induced increase in mean and anterograde SR (P > 0.05) but also increased retrograde SR (P < 0.05). In addition, increases in radial artery blood flow and diameter were reduced during Exercise + WC (Exercise + WC vs. Exercise, P < 0.05). After Exercise, L-FMC was augmented (− 4.4 ± 1.4 vs. − 13.1 ± 1.6%, P < 0.05), compared to no change in L-FMC after Exercise + WC (− 5.2 ± 2.0 vs. − 3.0 ± 1.6%, P > 0.05). In contrast, no change in FMD was observed in either Exercise or Exercise + WC trials (P > 0.05).ConclusionsThese findings indicate that increases in L-FMC following exercise are abolished by the prevention of increases radial artery diameter, mean and anterograde SR, and by elevation of retrograde SR, during exercise in young men.

What is the impact of aerobic fitness and movement interventions on low-flow-mediated vasoconstriction? A systematic review of observational and intervention studies.

The cardiovascular benefits of physical exercise are well established. The vasoreactivity that occurs during reductions in local arterial blood flow, termed low-flow-mediated constriction (L-FMC), is a measure of endothelial-dependent vasoconstrictor function. It is unclear whether aerobic fitness and movement (or lack thereof) influences L-FMC. We systematically reviewed studies examining the impact of physical behaviours on L-FMC. To be included, cross-sectional and interventional studies had to examine the impact of a physical behaviour on L-FMC in adults. There were no language or date of publication restrictions. Sources were searched in May, 2021 and included Scopus, Embase, MEDLINE, CINAHL, and Academic Search Premier. National Institutes of Health quality assessment tools were used. Fourteen studies (15 arms; 313 participants; 398 total observations from four arteries) met the inclusion criteria. The study quality varied from four out of 14 (controlled intervention scoring) to nine out of 12 (longitudinal intervention with no control group scoring) with the total points dependent upon the study design. Conflicting results were reported for acute prolonged sitting studies (attenuated L-FMC: n = 1; no change: n = 1) and resistance exercise (increased L-FMC: n = 2; no change: n = 2). Most observational studies examining aerobic fitness (3/4 studies) and aerobic exercise interventions (4/5 studies) observed a favourable effect on L-FMC. Overall, the included studies support that higher aerobic fitness and engaging in aerobic exercise training may augment L-FMC responses. Our systematic review highlights the heterogeneity between studies and identifies current gaps and future directions to better our understanding of (in)activity, exercise, and posture on endothelial vasoconstrictor function. PROSPERO Registration No.: CRD42021248241.

Central Blood Pressure and Subclinical Atherosclerotic Risk in Young Hispanic American Women.

The incidence of younger women being hospitalized from cardiovascular disease (CVD) events is on the rise. Hispanic women are generally thought to have higher CVD risk factor burden than non-Hispanic White (NHW) women yet Hispanic Americans have lower mortality from CVD. Traditional measures of CVD may not accurately capture CVD risk in Hispanic Americans. Hence, the purpose of this study was to assess the impact of ethnicity on vascular reactivity and central hemodynamic load to gain insight into subclinical CVD risk in young women. Brachial flow-mediated dilation (FMD), low-flow mediated constriction (L-FMC), carotid-femoral pulse wave velocity (cfPWV), and pulse wave analysis (from synthesized aortic pressure waveforms) were measured in 25 Hispanic women and 31 NHW women aged between 18-35 years. FMD and L-FMC were combined to provide an index of total vessel reactivity. NHW and Hispanic women did not differ in age or traditional CVD risk factors (P>.05 for all). Compared with NHW women, Hispanic women had greater vascular reactivity (8.7±4.1 vs 11.7±4.1 %, P=.011), lower central pulse pressure (28±5 vs 24±3 mm Hg, P=.001) and lower pressure from wave reflections (12±2 vs 10±1 mm Hg, P=.001). There were no differences in cfPWV between NHW women and Hispanic women (5.4±0.7 vs 5.3±0.7 m/s, P=.73). Young Hispanic women have greater vascular reactivity and lower central pulsatile hemodynamic load compared with NHW women, suggesting lower subclinical CVD risk.

A larger low-flow-mediated constrictor response is associated with augmented flow-mediated dilation in the popliteal artery.

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 110healthy participants (60 females; 42±22 [19-77] years). All variables univariately associated (p<0.05) with popliteal relative FMD (relative L-FMC, log-SRAUC , 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-SRAUC : 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.

Assessment of vascular function in formerly pre-eclamptic women as a novel marker of future cardiovascular risk

Abstract Funding Acknowledgements Type of funding sources: None. Background Women with a history of pre-eclampsia (PE) are at increased risk of cardiovascular disease (CVD). The association between PE and CVD in later life may be explained by vascular dysfunction, either pre-existing or elicited by PE. Several small studies have shown that vascular dysfunction may persist for years in some patients, indicator of future CVD risk, while other studies could not confirm these findings. Purpose In this longitudinal prospective cohort study, we aim to comprehensively assess vascular function in previously pre-eclamptic women (early (&amp;lt;34 weeks) and late (&amp;gt;34 weeks)) and healthy controls. We hypothesize that vascular dysfunction is both more persistent and pronounced in early PE compared to late PE since different pathophysiologic mechanisms underlie both subtypes of PE. Methods For this first analysis, 63 PE patients were compared to 16 non-pregnant healthy controls. Endothelial function was determined by flow-mediated dilatation (FMD), modified FMD (mFMD) and low-flow mediated constriction (L-FMC). Arterial stiffness was assessed by carotid-femoral pulse wave velocity (cfPWV) and augmentation index using pulse wave analysis of the brachial artery, and corrected for heart-rate (Aix75). Results Average post-partum period was 11 months (1.4-111.5 months). Thirty-five presented with early PE, 28 with late PE. In the total PE group, FMD was significantly decreased compared to healthy controls (7.1 ± 2.8 vs 8.9 ± 3.8; p = 0.037), but no difference between early and late PE was observed. Likewise, Aix75 remained elevated after PE (16.5 ± 11.5 vs 5.8 ± 10.1; p &amp;lt; 0.001), again, without difference between early and late PE. cfPWV was not different after PE compared to healthy controls (p &amp;gt; 0.05) but was significantly higher in the early PE group compared to the late PE group (6.9 ± 1.0 vs 6.4 ± 1.0; p = 0.045). Conclusion Even in the postpartum, PE is characterized by overt and persisting endothelial dysfunction and arterial stiffness. Arterial stiffness is more pronounced in early PE compared to late PE. This reaffirms that PE has consequences beyond placental impairment and that the persisting vascular impairment in the postpartum could reflect the risk of CVD later in life.

Endothelial function of healthy adults from 20 to 91 years of age: prediction of cardiovascular risk by vasoactive range.

Brachial arterial low flow-mediated constriction (L-FMC) and flow-mediated dilation (FMD) are ultrasound-based biomarkers that emerge into scientific and clinical practice indicating cardiovascular effects of medical and lifestyle-based treatment beyond classical risk factors. This study is the first to provide reference values and to assess the predictive value of L-FMC, FMD and their composite endpoint vasoactive range (VAR) in healthy adults. L-FMC, FMD and VAR were measured in 457 nonsmoking adults of 20-91 years without chronic diseases, medication, with normal heart function and very low cardiovascular risk. Sex-specific percentiles were calculated and predictive ability for elevated cardiovascular risk was assessed using receiver-operating characteristic (ROC) curves. From 20 to 91 years of age, L-FMC increased 86.1 and 105.3%, FMD decreased 63.6 and 47.1% and VAR decreased 58.3 and 55.2% in women and men, respectively. Area under the ROC curves was 0.54 (95% CI = 0.49-0.54) for L-FMC, 0.67 (95% CI = 0.62-0.67) for FMD and 0.72 (95% CI = 0.67-0.72) for VAR (P < 0.001). Discriminatory cut-offs for elevated risk were 0.24% for L-FMC (sensitivity = 0.42, specificity = 0.67), 6.4% for FMD (sensitivity = 0.71, specificity = 0.60) and 6.3% for VAR (sensitivity = 0.62, specificity = 0.73). This study demonstrates reduced endothelial function with aging in healthy men and women with very low cardiovascular risk. Percentiles crossed cut-offs for elevated cardiovascular risk between 50 and 55 years in men and 70 and 75 years in women, indicating higher risk for cardiovascular disease in men. VAR showed the highest ability to identify individuals with elevated cardiovascular risk, and should be included in the monitoring and treatment of accelerated vascular aging even in healthy individuals.

Brachial Artery “Low-Flow Mediated Constriction” Is Associated with Myocardial Perfusion Defect Severity and Mediated by an Altered Flow Pattern during Occlusion

Introduction: The relationship between low flow-mediated constriction (LFMC), a new proposed measure of endothelial function, with cardiovascular disease severity and its hypothesized stimulus, that is, low flow, has not been comprehensively evaluated. The study evaluated association between change in brachial artery diameter during constriction with severity of myocardial perfusion defect (PD) and alterations in different components of flow profile. Methods: Brachial artery responses to occlusion were assessed in 91 patients and 30 healthy subjects. Change in anterograde and retrograde blood flow velocities (delta anterograde blood flow velocity and retrograde blood flow velocity), anterograde shear rate and retrograde shear rate (delta ASR and RSR, respectively), and oscillatory shear index (delta) during forearm occlusion at 50 mm Hg above systolic pressure, from baseline was calculated. Myocardial perfusion was evaluated in patients using exercise single positron emission computed tomography and % myocardial PD was calculated from summed stress score. Results: LFMC emerged as independent predictor of defect severity after correcting for age and gender (p = 0.014). Sixty-seven patients (73.6%) and 15 healthy subjects (50%) showed constriction during occlusion. In stepwise backward regression analysis, RSR contributed 35.5% and ASR contributed 20.1% of the total 63.9% variability in artery diameter during occlusion. Conclusion: The results suggest that LFMC is independently associated with myocardial perfusion severity and is “mediated” by an altered flow profile during occlusion.

The impact of age and sex on popliteal artery endothelial-dependent vasodilator and vasoconstrictor function.

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.

P.09 Differential Low Flow Mediated Constriction (LFMC) Responses in Radial and Brachial Arteries of Healthy Humans are Attributed to Occlusion Induced Flow Changes

BackgroundLiterature describes differences in Low flow mediated constriction (LFMC) of radial versus brachial artery [1,2]. We investigated whether differences in occlusion induced changes in luminal flow and shear rates could explain the observed radial vs brachial differences in LFMC responses.MethodsTwenty Healthy volunteers (Age 23.50 ± 2.06 years) underwent examination of Brachial and radial arteries of both the arms. Arteries were visualized in Pulsed wave doppler in duplex mode (Vivid-e; GE Healthcare) using a 12 MHz probe at baseline and during low flow state produced using an occluding cuff placed around the forearm (for brachial artery) and over the wrist joint (for radial artery) inflated to supra-systolic pressures.ResultsLFMC in Radial artery was significantly higher than that of Brachial artery [delta LFMC of –0.58 mm (–0.24––0.76) in radial artery vs 0.03 mm (0.21––0.13) in brachial artery; p < 0.0001). Occlusion induced reduction in anterograde shear rate was comparatively higher in radial artery than brachial artery [–67.9% (–43––77) in radial vs –56.7% (–40.9––65.4) in brachial; p = 0.0098] whereas, the rise in retrograde shear rate and changes in oscillatory shear index were comparable between both. Percentage changes in anterograde shear rate and anterograde flow velocities emerged as independent predictors in the regression model that explained 86% of the variance in LFMC responses of brachial artery.ConclusionDiscrepancies in the LFMC responses of radial vs brachial artery could be attributed to the occlusion induced differences in the anterograde shear rate and anterograde flow velocities.

Impact of whole body passive heat stress and arterial shear rate modification on radial artery function in young men.

We sought to determine how whole body heating acutely influences radial artery function, characterized using flow-mediated dilation (FMD) and low-flow-mediated constriction (L-FMC), and the mechanistic role of shear rate modification on radial artery functional characteristics during heating. Eleven young healthy men underwent whole body heating (water-perfused suit) sufficient to raise the core temperature by +1°C. Trials were repeated with (heat + WC) and without (heat) the application of a wrist cuff located distal to the radial artery examined, known to prevent increases in mean and anterograde shear rates but increase retrograde shear rate. Radial artery characteristics were assessed throughout each trial, with FMD and L-FMC assessed before and upon reaching the target core temperature. Heat markedly increased radial artery mean and anterograde shear rates, along with radial artery diameter and blood flow (P < 0.05). Heat + WC abolished the heat-induced increase in mean and anterograde shear rates (P > 0.05) but markedly increased retrograde shear rate (P < 0.05). Concomitantly, increases in radial artery diameter and blood flow were decreased (heat + WC vs. heat, P < 0.05). Heat attenuated FMD (8.6 ± 1.2% vs. 2.2 ± 1.4%, P < 0.05), whereas no change in FMD was observed in heat + WC (7.8 ± 1.2% vs. 10.8 ± 1.2%, P > 0.05). In contrast, L-FMC was not different in either trial (P > 0.05). In summary, acute whole body heating markedly elevates radial artery shear rate, diameter, and blood flow and diminishes FMD. However, marked radial artery vasodilation and diminished FMD are absent when these shear rate changes are prevented. Shear rate modifications underpin the radial artery response to acute whole body heat stress, but further endothelium-dependent vasodilation (FMD) is attenuated likely as the vasodilatory range limit is approached.NEW & NOTEWORTHY We observed that acute whole body heating elevates radial artery shear rate, diameter, and blood flow. This results in a diminished flow-meditated dilatation (FMD) but does not change low-flow-mediated constriction (L-FMC). Preventing shear rate changes during whole body heating reduces radial artery vasodilation and reverses FMD reductions but has no effect on L-FMC. These findings indicate that shear rate changes underpin conduit artery responses to acute whole body heat stress, but further endothelium-dependent flow-mediated vasodilation is attenuated as the vasodilatory range limit is approached.

The Low–Flow-Mediated Arterial Constriction in the Upper Limbs of Healthy Human Subjects are Artery Specific and Handedness Independent

Low–flow-mediated constriction (LFMC) has been used to assess resting endothelial function in peripheral conduit arteries. The literature describes discrepancies in the behaviour of radial versus brachial artery in response to low-flow state, the reasons for which were not addressed in a systematic and scientific way. Moreover, the influence of handedness on observed LFMC responses has not been investigated. The present study aimed at systematic measurement and comparison of the LFMC responses in radial and brachial arteries of both dominant and non-dominant arms of healthy human volunteers. We also investigated the physiological factors associated with differential LFMC response of radial versus brachial artery in the same group of subjects. Longitudinal B mode ultrasonographic cine loops of radial and brachial arteries were acquired at baseline and after producing distal circulatory arrest. Cine loops were screen grabbed and analyzed later using automated edge detection algorithms to measure end-diastolic diameters. Distal circulatory arrest was produced over the proximal forearm (for the brachial artery) and over the wrist (for the radial artery) at 250 mm Hg for 5 min after baseline measurements. Results suggested that arterial location (p = 0.0001) and baseline diameter (p < 0.0021) emerged as independent predictors of LFMC response. Differences in the LFMC responses are handedness independent and could be attributed to the arterial location along with the differences in their baseline diameters.

High dietary sodium augments vascular tone and attenuates low-flow mediated constriction in salt-resistant adults

Low-flow mediated constriction (L-FMC) has emerged as a valuable and complementary measure of flow-mediated dilation (FMD) for assessing endothelial function non-invasively. High dietary sodium has been shown to impair FMD independent of changes in blood pressure (BP), but its effects on L-FMC are unknown. To test the hypothesis that high dietary sodium would attenuate brachial artery L-FMC in salt-resistant adults. Fifteen healthy, normotensive adults (29 ± 6years) participated in a controlled feeding study. Following a run-in diet, participants completed a 7-day low sodium (LS; 20mmol sodium/day) and 7-day high sodium (HS; 300mmol sodium/day) diet in randomized order. On the last day of each diet, 24h urine was collected and assessments of 24h ambulatory BP and L-FMC were performed. Salt-resistance was defined as a change in 24h ambulatory mean arterial pressure (MAP) between the LS and HS diets of ≤ 5mmHg. Resting vascular tone and L-FMC were calculated from ultrasound-derived arterial diameters. High dietary sodium increased serum sodium and urinary sodium excretion (p < 0.001 for both), but 24h MAP was unchanged (p = 0.16) by design. High dietary sodium augmented vascular tone (LS: 91 ± 23%, HS: 125 ± 56%, p = 0.01) and attenuated L-FMC (LS: - 0.58 ± 0.99%, HS: 0.17 ± 1.23%, p = 0.008). These findings in salt-resistant adults provide additional evidence that dietary sodium has adverse vascular effects independent of changes in BP.

Impact of High-Intensity Interval Training, Moderate-Intensity Continuous Training, and Resistance Training on Endothelial Function in Older Adults.

It is unclear if high-intensity interval training (HIIT) elicits superior improvements in brachial artery (BA) flow-mediated dilation (FMD) responses (i.e., endothelial-dependent vasodilation) than moderate-intensity continuous training (MICT) or resistance training (RT) in otherwise healthy older adults. Whether HIIT enhances lower-limb FMD responses and/or augments low flow-mediated constriction (L-FMC) (endothelial-dependent vasoconstriction) responses more than MICT or RT is also unknown. We tested the hypothesis that HIIT would improve BA and popliteal artery (POP) FMD and L-FMC responses more than MICT or RT in healthy older adults. Thirty-eight older adults (age, 67 ± 6 yr) performed 6 wk of either HIIT (2 × 20 min bouts alternating between 15-s intervals at 100% of peak power output [PPO] and passive recovery [0% PPO]; n = 12), MICT (34 min at 60% PPO; n = 12), or whole-body RT (8 exercises, 2 × 10 repetitions; n = 14). The L-FMC and FMD were measured before and after training using high-resolution ultrasound and quantified as the percent change in baseline diameter during distal cuff occlusion and after cuff release, respectively. Resting BA blood flow and vascular conductance (both, P < 0.003) were greater after HIIT only. The HIIT and MICT similarly increased BA-FMD (pre-post: both, P < 0.001), but only HIIT improved BA L-FMC (P < 0.001). Both HIIT and MICT similarly enhanced POP FMD and L-FMC responses (both, P < 0.045). Resistance training did not impact FMD or L-FMC responses in either artery (all, P > 0.20). HIIT and MICT, but not RT, similarly improved lower-limb vasodilator and vasoconstrictor endothelial function in older adults. Although HIIT and MICT groups enhanced BA vasodilator function, only HIIT improved resting conductance and endothelial sensitivity to low-flow in the BA. In the short-term, HIIT may be most effective at improving peripheral vascular endothelial function in older adults.

Sex does not influence impairments in popliteal endothelial-dependent vasodilator or vasoconstrictor responses following prolonged sitting

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.

Comparison Of Endothelial-dependent Vasodilatory And Vasoconstrictor Responses Between Upper- And Lower-Limb Arteries In Older Adults

Low-flow mediated constriction (L-FMC) provides important information about the acute effects of reduced shear stress on endothelial function. L-FMC has been mainly tested in upper-limb arteries, where an inverse association with VO2peak has been observed in younger adults. It is unclear if an L-FMC response exists in lower limb arteries, which are exposed to larger fluctuations in shear stress during traditional modes of aerobic exercise than the upper-limb. Furthermore, it is uncertain whether the same inverse relationship between L-FMC and VO2peak exists in older adults (OA). PURPOSE: Based on known differences in flow-mediated dilation (FMD) between upper- and lower limbs, we tested the hypothesis that heterogeneous L-FMC responses exist between the brachial- (BA) vs. popliteal (POP) arteries. We also expected that OA with greater aerobic fitness would have larger L-FMC responses in both arteries. METHODS: FMD and L-FMC were assessed in 47 OA (67±5 yr; 30F) using high-resolution duplex ultrasonography with commercial edge-detection and wall-tracking software. L-FMC was defined as the % decrease in lumen diameter in response to 5-min of distal ischemia. FMD was calculated as the % increase in lumen diameter following a reactive hyperemia. RESULTS: Larger FMD responses were observed in the BA vs. POP (4.7±1.6% vs. 3.3±2.0%; P<0.001), which were moderately correlated to each other (r=0.54; P<0.001). When allometrically scaled, the BA exhibited a greater L-FMC response than the POP (-1.3±1.6% vs. -0.4±1.6%; P=0.03). L-FMC responses in the BA vs. POP were not correlated with each other (r=0.22; P=0.14). As expected, VO2peak was associated with both BA-FMD (r=0.59; P<0.001) and POP-FMD (r=0.48; P=0.001). VO2peak was moderately correlated to BA L-FMC (r=-0.52; P<0.001) but strongly correlated to POP L-FMC (r=-0.73; P<0.001). CONCLUSION: The heterogeneous L-FMC responses between the BA and POP indicates that upper limb L-FMC responses do not represent a systemic measure of vasoconstrictor capacity. The stronger association between VO2peak and POP L-FMC suggests that larger local shear stress responses, induced by traditional lower-limb modes of aerobic exercise, may result in greater adaptations to low flow-mediated endothelial vasoconstrictor responsiveness.

Relationship between brachial and popliteal artery low-flow-mediated constriction in older adults: impact of aerobic fitness on vascular endothelial function.

We previously observed that brachial artery (BA) low-flow-mediated constriction (L-FMC) is inversely related to aerobic fitness (i.e., V̇o2peak) 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). V̇o2peak 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 V̇o2peak 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.

Effect of short‐term 17B‐estradiol on low‐flow‐mediated constriction in young women

Low‐flow mediated constriction (L‐FMC) examines vascular responses during a reduction in blood flow and provides a measure of resting shear‐stress dependent vascular tone. L‐FMC is a complementary measure to flow‐mediated dilation (FMD), and is blunted in patients with cardiovascular disease. 17β‐estradiol (E2) exerts positive effects on vascular endothelial health and can improve FMD. However, it is unknown whether E2 impacts L‐FMC.PURPOSEThe purpose of this study was to test the hypothesis that E2 administration would augment L‐FMC in young women.METHODSEleven young women (24±1 years, 24±1 kg/m2) have completed the study. To isolate the impact of E2, endogenous ovarian hormone production was suppressed with daily subcutaneous injections of a gonadotropin releasing hormone antagonist (GnRHant, 0.25 mg/day) for 10 days. E2 (0.1mg/day patch) was administered during the last 7 days of GnRHant. We measured changes in brachial artery diameter via ultrasound on day 3 of GnRHant and day 7 of E2 add‐back. A blood pressure cuff was placed just distal to the olecranon process and inflated to 200mmHg for five minutes. Images were recorded continuously at baseline (1‐minute), during occlusion (5‐minutes), and after cuff deflation (2‐minutes). L‐FMC was determined from the last 30 seconds of cuff inflation using the lowest average value and was reported as percent change from baseline diameter. FMD was calculated as a percent change from baseline to peak diameter after cuff deflation. Total vessel reactivity was calculated as the absolute value of L‐FMC and FMD. Results are reported as mean ± standard error.RESULTSBaseline diameter was similar between GnRHant (3.14 ± 0.12 mm) and E2 (3.08 ± 0.11 mm; p=0.3). L‐FMC tended to be greater during E2 administration (GnRHant −2.5 ± 0.5% vs. E2 −3.8 ± 0.5%; p=0.11). However, FMD (GnRHant 7.5 ± 0.7% vs. E2 7.6 ± 1.1%; p=0.92) and total vessel reactivity (GnRHant 10.0 ± 0.7% vs. E2 11.5 ± 1.2%; p=0.26) were not altered by E2.CONCLUSIONThese preliminary findings suggest that short term E2 administration may augment L‐FMC in young women. Additional data are needed to understand the impact of ovarian hormones on L‐FMC and its role in regulating vascular health.Support or Funding InformationNIH Grant P20 GM 103446, P20 GM 113125, U54 GM 104941, The University of Delaware Research Foundation, and AHA Award 16SDG30700015This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Reliability of low-flow vasoreactivity in the brachial artery of adolescents.

Macrovascular endothelial function is commonly assessed using flow-mediated dilation (FMD) and is nitric oxide (NO) dependent. However, the vasoreactivity to low flow during the FMD protocol may complement FMD interpretation. This study aimed to investigate in adolescents: (1) the day-to-day reliability of low-flow-mediated constriction (L-FMC) and composite vessel reactivity (CVR); and (2) the relationship between L-FMC and FMD. A retrospective analysis of data on 27 adolescents (14.3 ± 0.6 year, 12 males) was performed. Participants had two repeat measures, on separate days, of macrovascular function using high-resolution ultrasound for assessment of L-FMC, FMD, and CVR. On average, the L-FMC response was vasoconstriction on both days (-0.59 ± 2.22% and -0.16 ± 1.50%, respectively). In contrast, an inconsistent response to low flow (vasoconstriction, dilation, or no change) was observed on an individual level. Cohen's Kappa revealed poor agreement for classifying the L-FMC measurement between visits (k = 0.04, P > .05). Assessment of the actual vessel diameter was robust with a coefficient of variation of 1.7% (baseline and peak) and 2.7% (low-flow). The between-day correlation coefficient between measures was r = .18, r = .96 and r = .52 for L-FMC, FMD, and CVR, respectively. No significant correlation between FMD and L-FMC was observed for either visit (r = -.06 and r = -.07, respectively; P > .05). In adolescents, the low-flow vasoreactivity is inconsistent between days. Whereas the actual vessel diameter is reproducible, the measurement of L-FMC and CVR has poor between-day reliability compared to FMD. Finally, L-FMC, and FMD are not significantly correlated.