Impact of acute exposure to increased hydrostatic pressure and reduced shear rate on conduit artery endothelial function: a limb-specific response

2009 ◽  
Vol 297 (3) ◽  
pp. H1103-H1108 ◽  
Author(s):  
Jaume Padilla ◽  
Ryan D. Sheldon ◽  
Diana M. Sitar ◽  
Sean C. Newcomer

Unlike quadrupeds, humans exhibit a larger hydrostatic pressure in the lower limbs compared with the upper limbs during a major part of the day. It is plausible that repeated episodes of elevated pressure in the legs may negatively impact the endothelium, hence contributing to the greater predisposition of atherosclerosis in the legs. We tested the hypothesis that an acute exposure to increased hydrostatic pressure would induce conduit artery endothelial dysfunction. In protocol 1, to mimic the hemodynamic environment of the leg, we subjected the brachial artery to a hydrostatic pressure gradient (∼15 mmHg) by vertically hanging the arm for 3 h. Brachial artery flow-mediated dilation (FMD) was assessed in both arms before and following the intervention. In protocol 2, we directly evaluated popliteal artery FMD before and after a 3-h upright sitting (pressure gradient ∼48 mmHg) and control (supine position) intervention. Our arm-hanging model effectively resembled the hemodynamic milieu (high pressure and low shear rate) present in the lower limbs during the seated position. Endothelium-dependent vasodilation at the brachial artery was attenuated following arm hanging ( P < 0.05); however, contrary to our hypothesis, upright sitting did not have an impact on popliteal artery endothelial function ( P > 0.05). These data suggest an intriguing vascular-specific response to increased hydrostatic pressure and reduced shear rate. Further efforts are needed to determine if this apparent protection of the leg vasculature against an acute hydrostatic challenge is attributable to posture-induced chronic adaptations.

2011 ◽  
Vol 111 (1) ◽  
pp. 244-250 ◽  
Author(s):  
Dick H. J. Thijssen ◽  
Nicola Rowley ◽  
Jaume Padilla ◽  
Grant H. Simmons ◽  
M. Harold Laughlin ◽  
...  

Brachial artery flow-mediated dilation (FMD) is a strong predictor of future cardiovascular disease and is believed to represent a “barometer” of systemic endothelial health. Although a recent study [Padilla et al. Exp Biol Med (Maywood) 235: 1287–1291, 2010] in pigs confirmed a strong correlation between brachial and femoral artery endothelial function, it is unclear to what extent brachial artery FMD represents a systemic index of endothelial function in humans. We conducted a retrospective analysis of data from our laboratory to evaluate relationships between the upper (i.e., brachial artery) vs. lower limb (superficial femoral n = 75; popliteal artery n = 32) endothelium-dependent FMD and endothelium-independent glyceryl trinitrate (GTN)-mediated dilation in young, healthy individuals. We also examined the relationship between FMD assessed in both brachial arteries ( n = 42). There was no correlation between brachial and superficial femoral artery FMD ( r2 = 0.008; P = 0.46) or between brachial and popliteal artery FMD ( r2 = 0.003; P = 0.78). However, a correlation was observed in FMD between both brachial arteries ( r2 = 0.34; P < 0.001). Brachial and superficial femoral artery GTN were modestly correlated ( r2 = 0.13; P = 0.007), but brachial and popliteal artery GTN responses were not ( r2 = 0.08; P = 0.11). Collectively, these data indicate that conduit artery vasodilator function in the upper limbs (of healthy humans) is not predictive of that in the lower limbs, whereas measurement of FMD in one arm appears to be predictive of FMD in the other. These data do not support the hypothesis that brachial artery FMD in healthy humans represents a systemic index of endothelial function.


2019 ◽  
Vol 126 (6) ◽  
pp. 1687-1693 ◽  
Author(s):  
Sophie M. Holder ◽  
Ellen A. Dawson ◽  
Áine Brislane ◽  
Jonny Hisdal ◽  
Daniel J. Green ◽  
...  

Increase in mean shear stress represents an important and potent hemodynamic stimulus to improve conduit artery endothelial function in humans. No previous study has examined whether fluctuations in shear rate patterns, without altering mean shear stress, impacts conduit artery endothelial function. This study examined the hypothesis that 30-min exposure to fluctuations in shear rate patterns, in the presence of unaltered mean shear rate, improves brachial artery flow-mediated dilation. Fifteen healthy men (27.3 ± 5.0 yr) completed the study. Bilateral brachial artery flow-mediated dilation was assessed before and after unilateral exposure to 30 min of intermittent negative pressure (10 s, −40mmHg; 7 s, 0 mmHg) to induce fluctuation in shear rate, while the contralateral arm was exposed to a resting period. Negative pressure significantly increased shear rate, followed by a decrease in shear rate upon pressure release (both P < 0.001). Across the 30-min intervention, mean shear rate was not different compared with baseline ( P = 0.458). A linear mixed model revealed a significant effect of time observed for flow-mediated dilation ( P = 0.029), with exploratory post hoc analysis showing an increase in the intervention arm (∆FMD +2.0%, P = 0.008), but not in the contralateral control arm (∆FMD +0.5%, P = 0.664). However, there was no effect for arm ( P = 0.619) or interaction effect ( P = 0.096). In conclusion, we found that fluctuations in shear patterns, with unaltered mean shear, improves brachial artery flow-mediated dilation. These novel data suggest that fluctuations in shear pattern, even in the absence of altered mean shear, represent a stimulus to acute change in endothelial function in healthy individuals. NEW & NOTEWORTHY Intermittent negative pressure applied to the forearm induced significant fluctuations in antegrade and retrograde shear rate, while mean shear was preserved relative to baseline. Our exploratory study revealed that brachial artery flow-mediated dilation was significantly improved following 30-min exposure to intermittent negative pressure. Fluctuations in blood flow or shear rate, with unaltered mean shear, may have important implications for vascular health; however, further research is required to identify the underlying mechanisms and potential long-term health benefits.


2004 ◽  
Vol 287 (1) ◽  
pp. H374-H380 ◽  
Author(s):  
Patricia C. E. de Groot ◽  
Fleur Poelkens ◽  
Miriam Kooijman ◽  
Maria T. E. Hopman

The aim of the study was to assess endothelial function, measured by flow-mediated dilation (FMD), in an inactive extremity (leg) and chronically active extremity (arm) within one subject. Eleven male spinal cord-injured (SCI) individuals and eleven male controls (C) were included. Echo Doppler measurements were performed to measure FMD responses after 10 and 5 min of arterial occlusion of the leg (superficial femoral artery, SFA) and the arm (brachial artery, BA), respectively. A nitroglycerine spray was administered to determine the endothelium independent vasodilatation in the SFA. In the SFA, relative changes in FMD were significantly enhanced in SCI compared with C (SCI: 14.1 ± 1.3%; C: 9.2 ± 2.3%), whereas no differences were found in the BA (SCI: 12.5 ± 2.9%; C: 14.2 ± 3.3%). Because the FMD response is directly proportional to the magnitude of the stimulus, the FMD response was also expressed relative to the shear rate. No differences between the groups were found for the FMD-to-shear rate ratio in the SFA (SCI:0.061 ± 0.023%/s−1; C: 0.049 ± 0.024%/s−1), whereas the FMD-to-shear rate ratio was significantly decreased in the BA of SCI individuals (SCI: 0.037 ± 0.01%/s−1; C: 0.061 ± 0.027%/s−1). The relative dilatory response to nitroglycerine did not differ between the groups. (SCI: 15.6 ± 2.0%; C: 13.4 ± 2.3%). In conclusion, our results indicate that SCI individuals have a preserved endothelial function in the inactive legs and possibly an attenuated endothelial function in the active arms compared with controls.


2020 ◽  
Vol 129 (4) ◽  
pp. 637-645 ◽  
Author(s):  
Myles W. O’Brien ◽  
Jarrett A. Johns ◽  
Amera Al-Hinnawi ◽  
Derek S. Kimmerly

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.


2019 ◽  
Vol 127 (6) ◽  
pp. 1754-1762
Author(s):  
Gemma Kate Lyall ◽  
Matthew John Davies ◽  
Carrie Ferguson ◽  
Karen E. Porter ◽  
Karen M. Birch

Endothelial cell phenotype and endothelial function are regulated by hemodynamic forces, particularly wall shear stress (WSS). During a single bout of exercise, the specific exercise protocol can affect in-exercise WSS patterns and, consequently, endothelial function. MicroRNAs might provide a biomarker of in-exercise WSS pattern to indicate whether a specific exercise bout will have a positive effect on endothelial function. We evaluated the effect of acute interval (IT) and continuous (CON) in-exercise WSS patterns upon postexercise endothelial function and circulating microRNA (miR)-21 expression. Methods and results: 13 participants performed CON and 3 different IT exercise protocols matched for duration and intensity on separate days. Oxygen uptake, heart rate, and brachial artery blood flow were recorded throughout the exercise. Brachial artery flow-mediated dilation (FMD) was performed pre-exercise and 15 min postexercise. Plasma samples were acquired pre-exercise and 6 h postexercise to determine miR-21 expression. In-exercise shear rate (SR) patterns (a surrogate of WSS) differed according to the CON or IT work-rate profile. In-exercise anterograde SR was greater in CON than IT exercise ( P < 0.05), but retrograde SR was equivalent between exercise protocols ( P > 0.05). Oscillatory shear index was higher during IT versus CON exercise ( P < 0.05). Postexercise FMD increased (pre: 7.08% ± 2.95%, post: 10.54% ± 4.24%, P < 0.05), whereas miR-21 expression was unchanged (pre: 12.0% ± 20.7% cel-miR-39, post: 11.1 ± 19.3% cel-miR-39, P > 0.05) with no effect of exercise protocol ( P > 0.05). Conclusions: CON and IT exercise induced different SR patterns but equivalent improvements in acute endothelial function. The absence of change in miR-21 expression suggests that miR-21 is not a suitable biomarker of exercise-induced SR. NEW & NOTEWORTHY Interval exercise has the potential to negatively impact vascular adaptations because of repeated oscillations in vascular shear. To our knowledge, we are the first to continuously assess exercise-induced shear throughout different acute exercise protocols and examine its relationship with acute endothelial function and a circulating biomarker of shear (miR-21). These experiments provide clear data indicating enhancement of the acute vascular response from differing interval exercise protocols, with the study also providing detailed vascular and shear responses for future reference.


2021 ◽  
Vol 130 (1) ◽  
pp. 17-25
Author(s):  
Jennifer L. Petterson ◽  
Myles W. O’Brien ◽  
Jarrett A. Johns ◽  
Jack Chiasson ◽  
Derek S. Kimmerly

We compared changes in upper- and lower-limb artery endothelial-dependent vasodilatory and vasoconstrictor responses between control, prostaglandin inhibition, and endothelial-derived hyperpolarizing factor inhibition conditions. Neither prostaglandins nor endothelial-derived hyperpolarizing factor influenced flow-mediated dilation responses in either the brachial or popliteal artery. In contrast, endothelial-derived hyperpolarizing factor, but not prostaglandins, reduced resting brachial artery blood flow and shear rate and resting popliteal artery diameter, as well as low-flow-mediated constriction responses in both the popliteal and brachial arteries.


2005 ◽  
Vol 98 (6) ◽  
pp. 2185-2190 ◽  
Author(s):  
M. Rakobowchuk ◽  
C. L. McGowan ◽  
P. C. de Groot ◽  
J. W. Hartman ◽  
S. M. Phillips ◽  
...  

Given the increasing emphasis on performance of resistance exercise as an essential component of health, we evaluated, using a prospective longitudinal design, the potential for resistance training to affect arterial endothelial function. Twenty-eight men (23 ± 3.9 yr old; mean ± SE) engaged in 12 wk of whole body resistance training five times per week using a repeating split-body 3-day cycle. Brachial endothelial function was measured using occlusion cuff-induced flow-mediated dilation. After occlusion of the forearm for 4.5 min, brachial artery dilation and postocclusion blood flow was measured continuously for 15 and 70 s, respectively. Peak and 10-s postocclusion blood flow, shear rate, and brachial artery flow-mediated dilation (relative and normalized to shear rate) were measured pretraining (Pre), at 6 wk of training (Mid), and at 13 wk of training (Post). Results indicated an increase of mean brachial artery diameter by Mid and Post vs. Pre. Peak and 10-s postocclusion blood flow increased by Mid and remained elevated at Post; however, shear rates were not different at any time point. Relative and normalized flow-mediated dilation was also not different at any time point. This study is the first to show that peripheral arterial remodeling does occur with resistance training in healthy young men. In addition, the increase in postocclusion blood flow may indicate improved resistance vessel function. However, unlike studies involving endurance training, flow-mediated dilation did not increase with resistance training. Thus arterial adaptations with high-pressure loads, such as those experienced during resistance exercise, may be quite different compared with endurance training.


2012 ◽  
Vol 303 (5) ◽  
pp. H533-H538 ◽  
Author(s):  
Tom G. Bailey ◽  
Gurpreet K. Birk ◽  
N. Timothy Cable ◽  
Greg Atkinson ◽  
Daniel J. Green ◽  
...  

Strenuous exercise is associated with an immediate decrease in endothelial function. Repeated bouts of ischemia followed by reperfusion, known as remote ischemic preconditioning (RIPC), is able to protect the endothelium against ischemia-induced injury beyond the ischemic area. We examined the hypothesis that RIPC prevents the decrease in endothelial function observed after strenuous exercise in healthy men. In a randomized, crossover study, 13 healthy men performed running exercise preceded by RIPC of the lower limbs (4 × 5-min 220-mmHg bilateral occlusion) or a sham intervention (sham; 4 × 5-min 20-mmHg bilateral occlusion). Participants performed a graded maximal treadmill running test, followed by a 5-km time trial (TT). Brachial artery endothelial function was examined before and after RIPC or sham, as well as after the 5-km TT. We measured flow-mediated dilation (FMD), an index of endothelium-dependent function, using high-resolution echo-Doppler. We also calculated the shear rate area-under-the-curve (from cuff deflation to peak dilatation; SRAUC). Data are described as mean and 95% confidence intervals. FMD changed by <0.6% immediately after both ischemic preconditioning (IPC) and sham interventions ( P > 0.30). In the sham trial, FMD changed from 5.1 (4.4–5.9) to 3.7% (2.6–4.8) following the 5-km TT ( P = 0.02). In the RIPC trial, FMD changed negligibly from 5.4 (4.4–6.4) post-IPC and 5.7% (4.6–6.8) post 5-km TT ( P = 0.60). Baseline diameter, SRAUC, and time-to-peak diameter were all increased following the 5-km TT ( P < 0.05), but these changes did not influence the IPC-mediated maintenance of FMD. In conclusion, these data indicate that strenuous lower-limb exercise results in an acute decrease in brachial artery FMD of ∼1.4% in healthy men. However, we have shown for the first time that prior RIPC of the lower limbs maintains postexercise brachial artery endothelium-dependent function at preexercise levels.


2015 ◽  
Vol 100 (10) ◽  
pp. 1107-1117 ◽  
Author(s):  
J. O. Totosy de Zepetnek ◽  
D. S. Ditor ◽  
J. S. Au ◽  
M. J. MacDonald

2014 ◽  
Vol 307 (3) ◽  
pp. H418-H425 ◽  
Author(s):  
Ralph R. Scholten ◽  
Marc E. A. Spaanderman ◽  
Daniel J. Green ◽  
Maria T. E. Hopman ◽  
Dick H. J. Thijssen

Blood flow patterns in conduit arteries characterized by high levels of retrograde shear stress can be detrimental for vascular health. In this study we examined whether retrograde shear rate and endothelial function are related in healthy and formerly preeclamptic (PE) women and whether this relationship is altered by exercise training. Formerly PE women (32 ± 4 yr, n = 20) and controls (32 ± 4 yr, n = 20), all 6–12 mo postpartum, performed 12-wk aerobic exercise training. We measured brachial artery shear rate (SR) and endothelial function by flow-mediated dilation (FMD, echo-Doppler). We additionally performed power spectral analysis of heart rate variability and calculated low-frequency/high-frequency (LF/HF) ratio. Antegrade SR was not different between groups, while retrograde SR was significantly higher and FMD% lower in PE women compared with controls (both P < 0.05). Retrograde shear correlated strongly with FMD% in PE women and controls ( P < 0.05). LF/HF ratio inversely correlated with brachial artery retrograde SR and FMD% (both P < 0.05) in PE women and controls. Exercise training reduced retrograde shear, improved FMD%, and reduced LF/HF ratios similarly in both groups (all P < 0.05). Training-induced changes in retrograde SR correlated with changes in FMD% and LF/HF ratio. A higher brachial artery retrograde SR relates to lower brachial artery endothelial function, in both controls and formerly PE women. Exercise training improves retrograde SR, while the magnitude of this change correlated strongly with improvements in FMD and reductions in LF/HF ratio. Therefore, the impact of PE and exercise training on endothelial health may, at least partly, be related to retrograde shear rate.


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