Normal pregnancy is associated with enhanced endothelium-dependent flow-mediated vasodilation

1999 ◽  
Vol 276 (3) ◽  
pp. H821-H825 ◽  
Author(s):  
Inge Dørup ◽  
Kristjar Skajaa ◽  
Keld E. Sørensen

Normal pregnancy is characterized by reduced systemic vascular resistance, which may be mediated by nitric oxide (NO). We compared endothelial vasomotor function in 71 normal pregnant women (13 in first, 29 in middle, and 29 in last trimester) to 37 healthy age-matched controls. With external ultrasound, brachial artery diameter was measured at rest, during reactive hyperemia [with increased flow causing endothelium-dependent dilation (FMD)], and after sublingual nitroglycerin (causing endothelium-independent dilation). Compared with controls, resting flow and brachial artery diameter were significantly higher during the middle and last trimesters. Reactive hyperemia was reduced in all pregnant groups. FMD increased from the first trimester (by 26%), reaching the highest value in the last trimester (to 47% above nonpregnant values). FMD was significantly correlated to pregnancy status (nonpregnant or pregnant) and to vessel size. Nitroglycerin-induced dilation was similar in pregnant and nonpregnant women. A longitudinal study of eight women evaluated in the first, middle, and last trimesters confirmed an increase in FMD throughout pregnancy. The study supports the idea that basal and stimulated NO activity is enhanced in normal pregnancy and may contribute to the decrease in peripheral resistance.

2004 ◽  
Vol 97 (2) ◽  
pp. 499-508 ◽  
Author(s):  
Kyra E. Pyke ◽  
Erin M. Dwyer ◽  
Michael E. Tschakovsky

The reactive hyperemia test (RHtest) evokes a transient increase in shear stress as a stimulus for endothelial-dependent flow-mediated vasodilation (EDFMD). We developed a noninvasive method to create controlled elevations in brachial artery (BA) shear rate (SR, estimate of shear stress), controlled hyperemia test (CHtest), and assessed the impact of this vs. the RHtest approach on EDFMD. Eight healthy subjects participated in two trials of each test on 3 separate days. For the CHtest, SR was step increased from 8 to 50 s−1, created by controlled release of BA compression during forearm heating. For the RHtest, transient increases in SR were achieved after 5 min of forearm occlusion. BA diameter and blood flow velocity (ultrasound) were measured upstream of compression and occlusion sites. Both tests elicited significant dilation (RHtest: 6.33 ± 3.12%; CHtest: 3.00 ± 1.05%). The CHtest resulted in 1) reduced between-subject SR and EDFMD variability vs. the RHtest [SR coefficient of variation (CV): 4.9% vs. 36.6%; EDFMD CV: 36.16% vs. 51.80%] and 2) virtual elimination of the impact of BA diameter on the peak EDFMD response (peak EDFMD vs. baseline diameter for RHtest, r2 = 0.64, P < 0.01, vs. CHtest, r2 = 0.14, P < 0.01). Normalization of the RHtest EDFMD response to the magnitude of the SR stimulus eliminated test differences in between-subject response variability. Reductions in trial-to-trial and day-to-day SR variability with the CHtest did not reduce EDFMD variability. Between-subject SR variability contributes to EDFMD variability with the RHtest. SR controls with the CHtest or RHtest response normalization are essential for examining EDFMD between groups differing in baseline arterial diameter.


2001 ◽  
Vol 86 (1) ◽  
pp. 158-161 ◽  
Author(s):  
Samantha Worboys ◽  
Dimitra Kotsopoulos ◽  
Helena Teede ◽  
Barry McGrath ◽  
Susan R. Davis

The gender difference in cardiovascular disease has been partly attributed to higher androgenic hormone levels. Although testosterone in women may not affect lipids, it remains unknown whether it negates favorable estrogenic effects on endothelial function. We have investigated the effects of testosterone implant therapy on arterial reactivity encompassing endothelial-dependent and -independent vasodilation in women using hormone replacement therapy (HRT). B-mode ultrasound measurements of resting brachial artery diameter, following reactive hyperemia [endothelium-dependent flow- mediated dilation (FMD)] and following glyceryl trinitrate (GTN) (endothelium-independent dilation), were recorded in 33 postmenopausal women stabilized on HRT (&gt;6 months), at baseline, and 6 weeks after a testosterone implant (50 mg), with 15 postmenopausal nonusers of HRT serving as controls. In the brachial artery, baseline resting diameter was similar (0.40 ± 0.01 vs. 0.41 ± 0.01 cm, P = 0.5). In the treated group, testosterone levels increased (0.99 ± 0.08 to 4.99 ± 0.3 nmol/L, P &lt; 0.001), associated with a mean 42% increase in FMD (6.4% ± 0.7 to 9.1% ± 1.1, P = 0.03). The control group did not change (8.1% ± 1.4 to 5.6% ± 1.0, P = 0.4). ANOVA of repeated measures (P = 0.04) and mean change (P = 0.02) in FMD both demonstrated significantly greater improvement with testosterone compared with controls. GTN induced vasodilation increased with testosterone treatment (14.9% ± 0.9 to 17.8% ± 1.2, P = 0.03). Our preliminary data indicate that parenteral testosterone therapy improves both endothelial-dependent (flow-mediated) and endothelium-independent (GTN-mediated) brachial artery vasodilation in postmenopausal women using long-term estrogen therapy. The mechanisms underlying these potentially beneficial cardiovascular effects require further investigation.


2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Michelle M Harbin ◽  
Joseph D Ostrem ◽  
Nicholas G Evanoff ◽  
Aaron S Kelly ◽  
Donald R Dengel

Purpose: When assessing vasomotor endothelial function of the brachial artery by reactive hyperemia, blood flow is stopped and creates a period of low-flow mediated constriction (L-FMC). Little is known about how this parameter influences flow-mediated vasodilation (FMD). The purpose of this study was to better understand this relationship and to determine the intra- and inter-day reproducibility of brachial L-FMC in healthy adults. Methods: Brachial L-FMC and FMD were measured on 26 healthy, young adults (13 males, 13 females; 24.6 ± 2.7 years). Each subject had two assessments conducted on two separate visits, separated by a minimum of seven days. Brachial artery pre-occlusion baseline diameter was imaged during rest and prior to cuff-occlusion. Continuous imaging of the artery was captured during the last 20 seconds of cuff-occlusion to 180 seconds post-cuff release. An L-FMC was considered present if the relative change from pre-occlusion baseline to L-FMC artery diameter was less than -0.1%. Peak FMD was measured as the greatest 10-second average in brachial artery diameter following occlusion compared to pre-occlusion baseline. Results: Overall, there was a strong, positive correlation between increased brachial L-FMC and blunted FMD (visit 1 test 1: r=0.758, p <0.001; visit 1 test 2: r=0.706, p <0.001; visit 2 test 1: r=0.836, p <0.001; visit 2 test 2: 0.857, p <0.001). The reproducibility of intra- and inter-day L-FMC diameter were ICC = 0.627, CV = 54.4% and ICC = 0.734, CV = 43.5%, respectively. Conclusion: The results of the present study suggest that the degree of vasoconstriction to low-flow conditions influences the subsequent maximal dilation during reactive hyperemia. However, L-FMC in young adults is variable as evidenced by the weak inter- and intra-day reproducibility of the measure. Further research is needed to study brachial L-FMC reproducibility among varying subject populations and the implications L-FMC has on the interpretation of FMD results.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Keiichiro Yoshinaga ◽  
Yuuki Tomiyama ◽  
Satoshi Fujii ◽  
Saori Nishio ◽  
Noriki Ochi ◽  
...  

Introduction: Simple vascular function measurements are desirable for atherosclerosis risk assessments. Recently, we developed a novel modality of automated oscillometric method to measure a brachial artery’s vascular elastic modulus (V E ) and reported that V E is uninfluenced by blood pressure. Galectin-3 (Gal-3) expressed in endothelial cells regulates vascular fibrosis and is a molecular determinant of vascular stiffness. Hypothesis: We aimed to clarify whether V E selectively correlates with marker of vascular stiffness in chronic kidney disease (CKD). Methods: 12 moderate-to-severe CKD pts (mean eGFR 25.9±23.5 mL/min/1.73m 2 ) and 15 controls were studied. Rest V E in brachial artery was measured by new automated oscillometric detector. V E was defined as follows [VE =ΔPressure/ (100XΔarea/Area) mmHg/%]. Using ultrasound, the brachial artery diameter at rest and during reactive hyperemia [flow mediated dilatation (FMD) with endothelial-dependent dilatation] was measured. Gal-3 and interleukin-6 (IL-6), a representative inflammatory marker, were measured by enzyme-linked immune assay. Results: CKD had lower FMD (4.86±3.37 vs 9.05±2.98 %, P=0.003) and had attenuated V E than control (1.08±0.26 vs 0.83±0.17 mmHg/%, P=0.002). CKD had higher IL-6 (0.67±0.29 vs 0.29±0.33 pg/mL, P=0.003) and higher Gal-3 (20.0±12.4 vs. 5.84±2.83 pg/mL, P<0.001). V E was negatively correlated with %FMD (r=-0.46, P=0.015) and correlated with Gal-3 (r=0.40, P=0.036) but not in IL-6 (r=0.21, P=0.28). Conclusions: Attenuated vascular elasticity detected by this novel approach closely correlated with increase in Gal-3 and reduced FMD in CKD. This may indicate that the attenuated vascular elasticity selectively reflects vascular fibrosis as evidenced by Gal-3 and subsequent endothelial responses to vascular stiffness. Thus, this oscillometric measurement may be useful for detecting vascular fibrosis information and dysfunction in endothelium level.


2005 ◽  
Vol 98 (6) ◽  
pp. 2311-2315 ◽  
Author(s):  
Louise H. Naylor ◽  
Cara J. Weisbrod ◽  
Gerry O'Driscoll ◽  
Daniel J. Green

The purpose of this study was to establish valid indexes of conduit and resistance vessel structure in humans by using edge detection and wall tracking of high-resolution B-mode arterial ultrasound images, combined with synchronized Doppler waveform envelope analysis, to calculate conduit artery blood flow and diameter continuously across the cardiac cycle. Nine subjects aged 36.7 (9.2) yr underwent, on separate days, assessment of brachial artery blood flow and diameter response to 5-, 10-, and 15-min periods of forearm ischemia in the presence and absence of combined sublingual glyceryl trinitrate (GTN) administration. Two further sessions examined responses to ischemic exercise, one in combination with GTN. The peak brachial artery diameter was observed in response to the combination of ischemic exercise and GTN; a significant difference existed between resting brachial artery diameter and peak brachial artery diameter, indicating that resting diameter may be a poor measure of conduit vessel structure in vivo. Peak brachial artery flow was also observed in response to a combination of forearm ischemia exercise and GTN administration, the response being greater than that induced by periods of ischemia, GTN, or ischemic exercise alone. These data indicate that noninvasive indexes of conduit and resistance vessel structure can be simultaneously determined in vivo in response to a single, brief, stimulus and that caution should be applied in using resting arterial diameter as a surrogate measure of conduit artery structure in vivo.


2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Heli Saarelainen ◽  
Henna Kärkkäinen ◽  
Pirjo Valtonen ◽  
Kari Punnonen ◽  
Tomi Laitinen ◽  
...  

Background. Our objective was to evaluate endothelial function and markers of inflammation during and after pregnancy in normal pregnancies compared to pregnancies complicated with hypertension or preeclampsia (PE). Methods and Results. We measured endothelium-dependent brachial artery flow-mediated vasodilation (FMD) and high sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α) in 32 women with normal pregnancy and in 28 women whose pregnancy was complicated with hypertensive disorder in the second half of pregnancy and minimum 3-month postpartum. Enhancement of endothelial function was greater in hypertensive than normal pregnancies, the mean FMD% being 11.0% versus 8.8% during pregnancy (P=0.194) and 8.0% versus 7.9% postpartum (P=0.978). Concentrations of markers of inflammation were markedly increased in pregnant hypertensive group compared to those after delivery (hsCRP 4.5 versus 0.80 mg/L, P=0.023, IL-6 2.1 versus 1.2 pg/mL, P=0.006; TNF-α 1.9 versus 1.5 pg/mL, P=0.030). There were no statistically significant associations between the markers of inflammation and FMD. Conclusions. Brachial artery FMD was not attenuated in the third trimester hypertensive pregnancies compared to normal pregnancies, whereas circulating concentrations of hsCRP and IL-6 and TNF-α reacted to hypertensive complications.


1997 ◽  
Vol 2 (2) ◽  
pp. 87-92 ◽  
Author(s):  
Akimi Uehata ◽  
Eric H Lieberman ◽  
Marie D Gerhard ◽  
Todd J Anderson ◽  
Peter Ganz ◽  
...  

Coronary atherosclerosis is characterized by an early loss of endothelium-dependent vasodilation. However, the methods of assessing coronary endothelial function are invasive and difficult to repeat over time. Recently, a noninvasive ultrasound method has been widely used to measure flow-mediated dilation in the brachial artery as a surrogate test for endothelial function. We seek to further validate this method of measuring vascular function. The brachial artery diameters and blood flow of 20 normal volunteers (10 males and 10 females) were measured using high resolution (7.5 MHz) ultrasound and strain gauge plethysmography. Flow-mediated endothelium-dependent vasodilation was measured in the brachial artery during reactive hyperemia after 5 minutes of cuff occlusion in the upper arm. The brachial artery diameter increased maximally by 9.7 ± 4.3% from baseline at 1 min after cuff release and blood flow increased by 1002 ± 376%. Five min of cuff occlusion was sufficient to achieve 97 ± 6% of maximal brachial artery dilation and degree of dilation was not different whether the cuff was inflated proximally or distally to the image site. The intraobserver variability in measuring brachial diameters was 2.9 % and the variability of the hyperemic response was 1.4%. In young, healthy men and women, the baseline brachial artery diameter was the only factor that was predictive of the flow-mediated vasodilation response. The brachial noninvasive technique has been further validated by the determination of flow-mediated dilation. This method of assessing endothelial function may help to determine the importance of vasodilator dysfunction as a risk factor in the development of atherosclerosis.


2016 ◽  
Vol 41 (5) ◽  
pp. 528-537 ◽  
Author(s):  
David J. Slattery ◽  
Troy J.R. Stuckless ◽  
Trevor J. King ◽  
Kyra E. Pyke

Flow mediated dilation (FMD) stimulated by different shear stress stimulus profiles may recruit distinct transduction mechanisms, and provide distinct information regarding endothelial function. The purpose of this study was to determine whether obesity influences brachial artery FMD differently depending on the shear stress profile used for FMD assessment. The FMD response to a brief, intermediate, and sustained shear stress profile was assessed in obese (n = 9) and lean (n = 19) young men as follows: brief stimulus, standard reactive hyperemia (RH) following a 5 min forearm occlusion (5 min RH); intermediate stimulus, RH following a 15 min forearm occlusion (15 min RH); sustained stimulus, 10 min of handgrip exercise (HGEX). Brachial artery diameter and mean shear stress were assessed using echo and Doppler ultrasound, respectively, during each FMD test. There was no group difference in HGEX shear stress (p = 0.390); however, the obese group had a lower HGEX-FMD (5.2 ± 3.0% versus 11.5 ± 4.4%, p < 0.001). There was no group difference in 5 min RH-FMD (p = 0.466) or 15 min RH-FMD (p = 0.181); however, the shear stress stimulus was larger in the obese group. After normalization to the stimulus the 15 min RH-FMD (p = 0.002), but not the 5 min RH-FMD (p = 0.118) was lower in the obese group. These data suggest that obesity may have a more pronounced impact on the endothelium’s ability to respond to prolonged increases in shear stress.


2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Carlo Maria Avallone ◽  
Martina Nuzzo ◽  
Irene Rota ◽  
Nicola Persico ◽  
Stefano Carugo ◽  
...  

Abstract Aims Arterial hypertension (AH) is one of the main determinants of clinical disorders during pregnancy affecting 2% to 10% of pregnancies with a substantial public health impact. Both endothelial injury and increased vascular reactivity have been reported to be involved in the pathogenesis of pre-eclampsia syndrome. Abnormal patterns in brachial artery Doppler velocities have been shown to be predictive of pre-eclampsia in first trimester. The aim of this study is to investigate whether flow-mediated dilation (FMD) and Doppler flow derived-parameters can predict the occurrence of AH. Methods and results The study population consisted of pregnant women (mean age 32 years) who had been referred to the IRCCS Fondazione Ca’ Granda Policlinico of Milan. None of them had any medical issues and was taking any medications at the time of pregnancy. FMD was performed on left brachial artery according to expert recommendation. Measurements of brachial artery diameter and flow have been collected at rest, shortly before cuff release and then 5-, 15-, 30-, 60-, and 90-s during hyperaemia phase. Among Doppler measurements, systolic and diastolic velocity (Vs and Vd, respectively) as well as mean velocity (mean V) were considered. In addition, the pulsatility index (PI) and resistance index (RI) were calculated. A 3-months follow-up was planned in order to detect the presence of AH. All data were expressed as the median. U-test (Mann–Whitney analysis) was performed to test difference among hypertensives and non-hypertensives We recruited 48 women (median age 32 yeas) whose 4 (8.5%) developed AH during pregnancy. These latter had statistically significant higher systolic velocity measured at 5 s after the release of distal occlusion (126 cm/s vs. 173 cm/s; P &lt; 0.05). No other velocity Doppler data [diastolic velocity (Vd), mean velocity (mean V), PI, RI, TAMAX, and TAMEAN] showed a statistical significant association with AH development. Conclusions The present study suggests that the vascular assessment through Doppler during FMD procedure may foresee the development of hypertensive disorder in pregnancy. Our result provides the first evidence that the peak systolic velocity of brachial artery may represent a marker of early endothelial activation or damage, that can be directly involved in the pathophysiological mechanisms of the hypertensive disorders in pregnancy.


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