scholarly journals Contribution of nitric oxide to brachial artery vasodilation during progressive handgrip exercise in the elderly

2013 ◽  
Vol 305 (8) ◽  
pp. R893-R899 ◽  
Author(s):  
Joel D. Trinity ◽  
D. Walter Wray ◽  
Melissa A. H. Witman ◽  
Gwenael Layec ◽  
Zachary Barrett-O'Keefe ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Shear Rate ◽  
Brachial Artery ◽  
Vascular Function ◽  
The Elderly ◽  
Flow Mediated Dilation ◽  
Handgrip Exercise ◽  
Modest Contribution ◽  
Older Subjects ◽  
The Relationship

The reduction in nitric oxide (NO)-mediated vascular function with age has largely been determined by flow-mediated dilation (FMD). However, in light of recent uncertainty surrounding the NO dependency of FMD and the recognition that brachial artery (BA) vasodilation during handgrip exercise is predominantly NO-mediated in the young, we sought to determine the contribution of NO to BA vasodilation in the elderly using the handgrip paradigm. BA vasodilation during progressive dynamic (1 Hz) handgrip exercise performed at 3, 6, 9, and 12 kg was assessed with and without NO synthase (NOS) inhibition [intra-arterial NG-monomethyl-l-arginine (l-NMMA)] in seven healthy older subjects (69 ± 2 yr). Handgrip exercise in the control condition evoked significant BA vasodilation at 6 (4.7 ± 1.4%), 9 (6.5 ± 2.2%), and 12 kg (9.5 ± 2.7%). NOS inhibition attenuated BA vasodilation, as the first measurable increase in BA diameter did not occur until 9 kg (4.0 ± 1.8%), and the change in BA diameter at 12 kg was reduced by ∼30% (5.1 ± 2.2%), with unaltered shear rate (Control: 407 ± 57, l-NMMA: 427 ± 67 s−1). Although shifted downward, the slope of the relationship between BA diameter and shear rate during handgrip exercise was unchanged (Control: 0.0013 ± 0.0004, l-NMMA: 0.0011 ± 0.007, P = 0.6) as a consequence of NOS inhibition. Thus, progressive handgrip exercise in the elderly evokes a robust BA vasodilation, the magnitude of which was only minimally attenuated following NOS inhibition. This modest contribution of NO to BA vasodilation in the elderly supports the use of the handgrip exercise paradigm to assess NO-dependent vasodilation across the life span.

scholarly journals Ascorbic acid improves brachial artery vasodilation during progressive handgrip exercise in the elderly through a nitric oxide-mediated mechanism

2016 ◽  
Vol 310 (6) ◽  
pp. H765-H774 ◽  
Author(s):  
Joel D. Trinity ◽  
D. Walter Wray ◽  
Melissa A. H. Witman ◽  
Gwenael Layec ◽  
Zachary Barrett-O'Keefe ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Ascorbic Acid ◽  
Free Radical ◽  
Brachial Artery ◽  
Vascular Function ◽  
The Elderly ◽  
Voluntary Contraction ◽  
Dependent Manner ◽  
Handgrip Exercise ◽  
Age Related

The proposed mechanistic link between the age-related attenuation in vascular function and free radicals is an attractive hypothesis; however, direct evidence of free radical attenuation and a concomitant improvement in vascular function in the elderly is lacking. Therefore, this study sought to test the hypothesis that ascorbic acid (AA), administered intra-arterially during progressive handgrip exercise, improves brachial artery (BA) vasodilation in a nitric oxide (NO)-dependent manner, by mitigating free radical production. BA vasodilation (Doppler ultrasound) and free radical outflow [electron paramagnetic resonance (EPR) spectroscopy] were measured in seven healthy older adults (69 ± 2 yr) during handgrip exercise at 3, 6, 9, and 12 kg (∼13–52% of maximal voluntary contraction) during the control condition and nitric oxide synthase (NOS) inhibition via NG-monomethyl-l-arginine (l-NMMA), AA, and coinfusion of l-NMMA + AA. Baseline BA diameter was not altered by any of the treatments, while l-NMMA and l-NMMA + AA diminished baseline BA blood flow and shear rate. AA improved BA dilation compared with control at 9 kg (control: 6.5 ± 2.2%, AA: 10.9 ± 2.5%, P = 0.01) and 12 kg (control: 9.5 ± 2.7%, AA: 15.9 ± 3.7%, P < 0.01). NOS inhibition blunted BA vasodilation compared with control and when combined with AA eliminated the AA-induced improvement in BA vasodilation. Free radical outflow increased with exercise intensity but, interestingly, was not attenuated by AA. Collectively, these results indicate that AA improves BA vasodilation in the elderly during handgrip exercise through an NO-dependent mechanism; however, this improvement appears not to be the direct consequence of attenuated free radical outflow from the forearm.

Low flow-mediated constriction occurs in the radial but not the brachial artery in healthy pregnant and nonpregnant women

2010 ◽  
Vol 108 (5) ◽  
pp. 1097-1105 ◽  
Author(s):  
Tracey L. Weissgerber ◽  
Gregory A. L. Davies ◽  
Michael E. Tschakovsky
Keyword(s):  
Shear Rate ◽  
Pregnant Women ◽  
Radial Artery ◽  
Brachial Artery ◽  
Vascular Function ◽  
Low Flow ◽  
Flow Mediated Dilation ◽  
Brachial Artery Diameter ◽  
Function Test ◽  
Positive Correlations

Radial artery diameter decreases when a wrist cuff is inflated to stop blood flow to distal tissue. This phenomenon, referred to as low flow-mediated vasoconstriction (L-FMC), was proposed as a vascular function test. Recommendations that L-FMC be measured concurrently with flow-mediated dilation (FMD) were based on radial artery data. However, cardiovascular disease prediction studies traditionally measure brachial artery FMD. Therefore, studies should determine whether L-FMC occurs in the brachial artery. The hypothesis that reduced shear causes L-FMC has not been tested. Brachial and radial artery L-FMC and FMD were assessed in active nonpregnant ( n = 17), inactive nonpregnant ( n = 10), active pregnant ( n = 15, 34.1 ± 1.2 wk gestation), and inactive pregnant ( n = 8, 34.2 ± 2.2 wk gestation) women. Radial artery diameter decreased significantly during occlusion in all groups (nonpregnant, −4.4 ± 4.2%; pregnant, −6.4 ± 3.2%). Brachial artery diameter did not change in active and inactive nonpregnant, and inactive pregnant women; however, the small decrease in active pregnant women was significant. Occlusion decreased shear rate in both arteries, yet L-FMC only occurred in the radial artery. Radial artery L-FMC was not correlated with the reduction in shear rate. L-FMC occurs in the radial but not the brachial artery and is not related to changes in shear rate. Positive correlations between L-FMC (negative values) and FMD (positive values) suggest that radial artery FMD may be reduced among women who experience greater L-FMC. Studies should clarify the underlying stimulus and mechanisms regulating L-FMC, and test the hypothesis that endothelial dysfunction is manifested as enhanced brachial artery L-FMC, but attenuated radial artery L-FMC.

scholarly journals Does arterial shear explain the magnitude of flow-mediated dilation?: a comparison between young and older humans

2009 ◽  
Vol 296 (1) ◽  
pp. H57-H64 ◽  
Author(s):  
Dick H. J. Thijssen ◽  
Lauren M. Bullens ◽  
Marieke M. van Bemmel ◽  
Ellen A. Dawson ◽  
Nicola Hopkins ◽  
...  
Keyword(s):  
Brachial Artery ◽  
Vascular Function ◽  
Ultrasound Images ◽  
Flow Mediated Dilation ◽  
Healthy Children ◽  
Time To Peak ◽  
Flow Mediated Dilatation ◽  
Young Subjects ◽  
S Peak ◽  
The Relationship

Flow-mediated dilatation (FMD) has become a commonly applied approach for the assessment of vascular function and health in humans. Recent studies emphasize the importance of normalizing the magnitude of FMD to its apparent eliciting stimulus, the postdeflation arterial shear. However, the relationship between shear stress and the magnitude of FMD may differ between groups. The aim of this study was to examine the relationship between the brachial FMD and four different indexes of postdeflation shear rate (SR) in healthy children ( n = 51, 10 ± 1 yr) and young ( n = 57, 27 ± 6 yr) and older ( n = 27, 58 ± 4 yr) adults. SR was calculated from deflation ( time 0) until 9 s (peak), 30 s (0–30), 60 s (0–60), or until the time-to-peak diameter in each individual (0-ttp). Edge detection and wall tracking of high resolution B-mode arterial ultrasound images were used to calculate the conduit artery diameter. In young adults, the brachial artery FMD demonstrated a significant correlation with the area under the SR curve (SRAUC) 0–30 s ( r2 = 0.12, P = 0.009), 0–60 s ( r2 = 0.14, P = 0.005), and 0-ttp ( r2 = 0.14, P = 0.005) but not for the peak SRAUC 0–9 s ( r2 = 0.04, P = 0.12). In children and older adults, the magnitude of the brachial artery FMD did not correlate with any of the four SRAUC stimuli. These findings suggest that in young subjects, postdeflation SRAUC correlates moderately with the magnitude of the FMD response. However, the relationship between FMD and postdeflation shear appears to be age dependent, with less evidence for an association in younger and older subjects. Therefore, we support presenting SRAUC stimuli but not normalizing FMD responses for the SRAUC when using this technique.

scholarly journals Exercise-induced brachial artery vasodilation: effects of antioxidants and exercise training in elderly men

2010 ◽  
Vol 298 (2) ◽  
pp. H671-H678 ◽  
Author(s):  
Anthony J. Donato ◽  
Abhimanyu Uberoi ◽  
Damian M. Bailey ◽  
D. Walter Wray ◽  
Russell S. Richardson
Keyword(s):  
Exercise Training ◽  
Brachial Artery ◽  
Vascular Function ◽  
Knee Extensor ◽  
The Elderly ◽  
Young Group ◽  
Handgrip Exercise ◽  
Age Related ◽  
Young Subjects ◽  
Exercise Induced

Aging, vascular function, and exercise are thought to have a common link in oxidative stress. Of the 28 subjects studied (young, 26 ± 2 yr; old, 71 ± 6 yr), 12 took part in a study to validate an antioxidant cocktail (AOC: vitamins C, E, and α-lipoic acid), while the remaining 8 young and 8 old subjects performed submaximal forearm handgrip exercise with placebo or AOC. Old subjects repeated forearm exercise with placebo or AOC following knee-extensor (KE) exercise training. Brachial arterial diameter and blood velocity (Doppler ultrasound) were measured at rest and during exercise. During handgrip exercise, brachial artery vasodilation in the old subjects was attenuated compared with that in young subjects following placebo (maximum = ∼3.0 and ∼6.0%, respectively). In contrast to the previously documented attenuation in exercise-induced brachial artery vasodilation in the young group with AOC, in the old subjects the AOC restored vasodilation (maximum = ∼7.0%) to match the young. KE training also improved exercise-induced brachial artery vasodilation. However, in the trained state, AOC administration no longer augmented brachial artery vasodilation in the elderly, but rather attenuated it. These data reveal an age-related pro-/antioxidant imbalance that impacts vascular function and show that exercise training is capable of restoring equilibrium such that vascular function is improved and the AOC-mediated reduction in free radicals now negatively impacts brachial artery vasodilation, as seen in the young.

scholarly journals Progressive handgrip exercise: evidence of nitric oxide-dependent vasodilation and blood flow regulation in humans

2011 ◽  
Vol 300 (3) ◽  
pp. H1101-H1107 ◽  
Author(s):  
D. Walter Wray ◽  
Melissa A. H. Witman ◽  
Stephen J. Ives ◽  
John McDaniel ◽  
Anette S. Fjeldstad ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Shear Stress ◽  
Shear Rate ◽  
Vascular Endothelial Cells ◽  
Peripheral Circulation ◽  
No Synthase ◽  
Handgrip Exercise ◽  
Endothelial No Synthase ◽  
Exercise Induced ◽  
The Relationship

In the peripheral circulation, nitric oxide (NO) is released in response to shear stress across vascular endothelial cells. We sought to assess the degree to which NO contributes to exercise-induced vasodilation in the brachial artery (BA) and to determine the potential of this approach to noninvasively evaluate NO bioavailability. In eight young (25 ± 1 yr) healthy volunteers, we used ultrasound Doppler to examine BA vasodilation in response to handgrip exercise (4, 8, 12, 16, 20, and 24 kg) with and without endothelial NO synthase blockade [intra-arterial NG-monomethyl-l-arginine (l-NMMA), 0.48 mg·dl−1·min−1]. Higher exercise intensities evoked significant BA vasodilation (4–12%) that was positively correlated with the hyperemic stimulus ( r = 0.98 ± 0.003, slope = 0.005 ± 0.001). During NO blockade, BA vasodilation at the highest exercise intensity was reduced by ∼70% despite similar exercise-induced increases in shear rate (control, +224 ± 30 s−1; l-NMMA, +259 ± 46 s−1). The relationship and slope of BA vasodilation with increasing shear rate was likewise reduced ( r = 0.48 ± 0.1, slope = 0.0007 ± 0.0005). We conclude that endothelial NO synthase inhibition with l-NMMA abolishes the relationship between shear stress and BA vasodilation during handgrip exercise, providing clear evidence of NO-dependent vasodilation in this experimental model. These results support this paradigm as a novel and valid approach for a noninvasive assessment of NO-dependent vasodilation in humans.

scholarly journals The impact of baseline diameter on flow-mediated dilation differs in young and older humans

2008 ◽  
Vol 295 (4) ◽  
pp. H1594-H1598 ◽  
Author(s):  
Dick H. J. Thijssen ◽  
Marieke M. van Bemmel ◽  
Lauren M. Bullens ◽  
Ellen A. Dawson ◽  
Nicola D. Hopkins ◽  
...  
Keyword(s):  
Brachial Artery ◽  
Vascular Function ◽  
Flow Mediated Dilation ◽  
Healthy Children ◽  
Cuff Inflation ◽  
Brachial Artery Diameter ◽  
Age Dependent ◽  
Older Subjects ◽  
The Impact ◽  
Baseline Diameter

Flow-mediated dilation (FMD) has become a commonly applied approach for the assessment of vascular function and health, but methods used to calculate FMD differ between studies. For example, the baseline diameter used as a benchmark is sometimes assessed before cuff inflation, whereas others use the diameter during cuff inflation. Therefore, we compared the brachial artery diameter before and during cuff inflation and calculated the resulting FMD in healthy children ( n = 45; 10 ± 1 yr), adults ( n = 31; 28 ± 6 yr), and older subjects ( n = 22; 58 ± 5 yr). Brachial artery FMD was examined after 5 min of distal ischemia. Diameter was determined from either 30 s before cuff inflation or from the last 30 s during cuff inflation. Edge detection and wall tracking of high resolution B-mode arterial ultrasound images was used to calculate conduit artery diameter. Brachial artery diameter during cuff inflation was significantly larger than before inflation in children ( P = 0.02) and adults ( P < 0.001) but not in older subjects ( P = 0.59). Accordingly, FMD values significantly differed in children (11.2 ± 5.1% vs. 9.4 ± 5.2%; P = 0.02) and adults (7.3 ± 3.2% vs. 4.6 ± 3.3%; P < 0.001) but not in older subjects (6.3 ± 3.4% vs. 6.0 ± 4.2%; P = 0.77). When the diameter before cuff inflation was used, an age-dependent decline was evident in FMD, whereas FMD calculated using the diameter during inflation was associated with higher FMD values in older than younger adults. In summary, the inflation of the cuff significantly increases brachial artery diameter, which results in a lower FMD response. This effect was found to be age dependent, which emphasizes the importance of using appropriate methodology to calculate the FMD.

The Influence of Muscle Mass on Shear Rate and Brachial Artery Flow Mediated Dilation in the Elderly

2007 ◽  
Vol 39 (Supplement) ◽  
pp. S428
Author(s):  
Devon A. Dobrosielski ◽  
Arturo A. Arce Esquivel ◽  
Kim Landry ◽  
Eric Ravussin ◽  
Michael A. Welsch
Keyword(s):  
Shear Rate ◽  
Muscle Mass ◽  
Brachial Artery ◽  
The Elderly ◽  
Flow Mediated Dilation ◽  
Artery Flow

P8.08 THE RELATIONSHIP BETWEEN BRACHIAL ARTERY FLOW-MEDIATED DILATION AND SHEAR RATE IN INDIVIDUALS WITH INCREASED CARDIOVASCULAR RISK

2011 ◽  
Vol 5 (4) ◽  
pp. 184
Author(s):  
K. Aizawa ◽  
S. Elyas ◽  
F. D’Abate ◽  
D. Majekolagbe ◽  
A.C. Shore ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
Shear Rate ◽  
Brachial Artery ◽  
Flow Mediated Dilation ◽  
Artery Flow ◽  
The Relationship

Are the dynamic response characteristics of brachial artery flow-mediated dilation sensitive to the magnitude of increase in shear stimulus?

2008 ◽  
Vol 105 (1) ◽  
pp. 282-292 ◽  
Author(s):  
K. E. Pyke ◽  
J. A. Hartnett ◽  
M. E. Tschakovsky
Keyword(s):  
Shear Stress ◽  
Shear Rate ◽  
Dynamic Response ◽  
Phase I ◽  
Brachial Artery ◽  
Flow Mediated Dilation ◽  
Final Phase ◽  
Stimulus Magnitude ◽  
Brachial Artery Diameter ◽  
Response Characteristics

The purpose of this study was to determine the dynamic characteristics of brachial artery dilation in response to step increases in shear stress [flow-mediated dilation (FMD)]. Brachial artery diameter (BAD) and mean blood velocity (MBV) (Doppler ultrasound) were obtained in 15 healthy subjects. Step increases in MBV at two shear stimulus magnitudes were investigated: large (L; maximal MBV attainable), and small (S; MBV at 50% of the large step). Increase in shear rate (estimate of shear stress: MBV/BAD) was 76.8 ± 15.6 s−1 for L and 41.4 ± 8.7 s−1 for S. The peak %FMD was 14.5 ± 3.8% for L and 5.7 ± 2.1% for S ( P < 0.001). Both the L (all subjects) and the S step trials (12 of 15 subjects) elicited a biphasic diameter response with a fast initial phase (phase I) followed by a slower final phase. Relative contribution of phase I to total FMD when two phases occurred was not sensitive to shear rate magnitude ( r2 = 0.003, slope P = 0.775). Parameters quantifying the dynamics of the FMD response [time delay (TD), time constant (τ)] were also not sensitive to shear rate magnitude for both phases (phase I: TD r2 = 0.03, slope P = 0.376, τ r2 = 0.04, slope P = 0.261; final phase: TD r2 = 0.07, slope P = 0.169, τ r2 = 0.07, slope P = 0.996). These data support the existence of two distinct mechanisms, or sets of mechanisms, in the human conduit artery FMD response that are proportionally sensitive to shear stimulus magnitude and whose dynamic response is not sensitive to shear stimulus magnitude.

scholarly journals CORP: Ultrasound assessment of vascular function with the passive leg movement technique

2017 ◽  
Vol 123 (6) ◽  
pp. 1708-1720 ◽  
Author(s):  
Jayson R. Gifford ◽  
Russell S. Richardson
Keyword(s):  
Vascular Function ◽  
Cardiovascular Health ◽  
Vascular System ◽  
The Elderly ◽  
Passive Movement ◽  
Flow Mediated Dilation ◽  
Peripheral Vascular ◽  
Ultrasound Assessment ◽  
Leg Movement ◽  
Hyperemic Response

As dysfunction of the vascular system is an early, modifiable step in the progression of many cardiovascular diseases, there is demand for methods to monitor the health of the vascular system noninvasively in clinical and research settings. Validated by very good agreement with more technical assessments of vascular function, like intra-arterial drug infusions and flow-mediated dilation, the passive leg movement (PLM) technique has emerged as a powerful, yet relatively simple, test of peripheral vascular function. In the PLM technique, the change in leg blood flow elicited by the passive movement of the leg through a 90° range of motion is quantified with Doppler ultrasound. This relatively easy-to-learn test has proven to be ≤80% dependent on nitric oxide bioavailability and is especially adept at determining peripheral vascular function across the spectrum of cardiovascular health. Indeed, multiple reports have documented that individuals with decreased cardiovascular health such as the elderly and those with heart failure tend to exhibit a substantially blunted PLM-induced hyperemic response (~50 and ~85% reduction, respectively) compared with populations with good cardiovascular health such as young individuals. As specific guidelines have not yet been put forth, the purpose of this Cores of Reproducibility in Physiology (CORP) article is to provide a comprehensive reference for the assessment and interpretation of vascular function with PLM with the aim to increase reproducibility and consistency among studies and facilitate the use of PLM as a research tool with clinical relevance.

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