Flow-mediated Dilation In Humans Research Articles

The effects of alcohol consumption on flow-mediated dilation in humans: A systematic review.

Changes in endothelial function may contribute to the positive and negative effects of alcohol consumption on cardiovascular conditions, such as hypertension and coronary artery disease. Numerous studies have used brachial artery flow‐mediated dilation (FMD) to examine the effects of alcohol consumption on endothelial function in humans. However, the findings are inconsistent and may be due to multiple factors such as heterogeneity in subject characteristics, the alcohol use pattern, and amount/dose of alcohol consumed. Therefore, the aim of this systematic review was to investigate the effect of alcohol consumption on brachial artery FMD in humans considering the above‐mentioned factors. This review found that while light to moderate alcohol consumption may have minimal effects on FMD, heavy alcohol consumption was associated with a decrease in FMD. However, most of the published studies included healthy, younger, and male individuals, limiting generalizability to other populations. Future studies should include more women, older subjects, and those from diverse and underrepresented backgrounds.

Expert consensus and evidence-based recommendations for the assessment of flow-mediated dilation in humans.

Endothelial dysfunction is involved in the development of atherosclerosis, which precedes asymptomatic structural vascular alterations as well as clinical manifestations of cardiovascular disease (CVD). Endothelial function can be assessed non-invasively using the flow-mediated dilation (FMD) technique. Flow-mediated dilation represents an endothelium-dependent, largely nitric oxide (NO)-mediated dilatation of conduit arteries in response to an imposed increase in blood flow and shear stress. Flow-mediated dilation is affected by cardiovascular (CV) risk factors, relates to coronary artery endothelial function, and independently predicts CVD outcome. Accordingly, FMD is a tool for examining the pathophysiology of CVD and possibly identifying subjects at increased risk for future CV events. Moreover, it has merit in examining the acute and long-term impact of physiological and pharmacological interventions in humans. Despite concerns about its reproducibility, the available evidence shows that highly reliable FMD measurements can be achieved when specialized laboratories follow standardized protocols. For this purpose, updated expert consensus guidelines for the performance of FMD are presented, which are based on critical appraisal of novel technical approaches, development of analysis software, and studies exploring the physiological principles underlying the technique. Uniformity in FMD performance will (i) improve comparability between studies, (ii) contribute to construction of reference values, and (iii) offer an easy accessible and early marker of atherosclerosis that could complement clinical symptoms of structural arterial disease and facilitate early diagnosis and prediction of CVD outcomes.

Effects of Allopurinol on Endothelial Function: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials.

Uric acid (UA), the final product of purine catabolism, may be associated with an increased risk of cardiovascular disease. The aim of this meta-analysis of randomized placebo-controlled trials was to evaluate whether lowering serum UA (SUA) levels with allopurinol is associated with improved flow-mediated dilation (FMD), a validated marker of early vascular damage. A literature search was carried out from inception until 20 June 2017. Meta-analysis was performed using an inverse variance-weighted, random-effects model with standardized mean difference (SMD) as the effect size estimate. Meta-analysis of data from the ten eligible randomized controlled trials (RCTs), with 670 subjects, suggested a significant increase in FMD following allopurinol treatment (weighted mean difference [WMD] 1.79%, 95% confidence interval [CI] 1.01-2.56, p<0.001; I 2: 86.77%). The effect size was robust and remained significant after omission of each single study. Subgroup analyses of RCTs based on the administered dose or duration of treatment did not reveal any significant impact of these variables on FMD change. Nor was a significant association found between allopurinol-induced changes in SUA levels and FMD (slope 0.46, p=0.253), whereas baseline FMD significantly influenced the degree of FMD improvement following allopurinol treatment (slope 0.52, p=0.022). Nitroglycerin-mediated dilation was not altered by allopurinol treatment (WMD 0.88%, 95% CI -1.15-2.91, p=0.395; I 2: 80.88%). This meta-analysis of available RCTs suggests a significant benefit from allopurinol intake in increasing FMD in humans, independent of its effect on SUA levels.

Ultrasound Assessment of Flow-Mediated Dilation of the Brachial and Superficial Femoral Arteries in Rats

Arterial vasodilation to increases in wall shear rate is indicative of vascular endothelial function. In humans, the non-invasive measurement of endothelial function can be achieved by employing the flow-mediated dilation technique, typically performed in the brachial or superficial femoral artery. Briefly, a blood pressure cuff placed distal to an ultrasound probe is inflated to a suprasystolic pressure, which results in limb ischemia. After 5 min of occlusion the cuff is deflated, resulting in reactive hyperemia and increases in wall shear rate that signal vasodilatory molecules to be released from the endothelium eliciting vasodilation. Despite the thousands of studies performing flow-mediated dilation in humans, surprisingly, no studies have performed this technique non-invasively in living rats. Considering the recent shift in focus to translational research, the establishment of guidelines for non-invasive measurement of flow-mediated dilation in rats and other rodents would be extremely valuable. In the following article, a protocol is presented for the non-invasive measurement of flow-mediated dilation in brachial and superficial femoral arteries of rats, as those sites are most commonly measured in humans.

High dietary sodium reduces brachial artery flow-mediated dilation in humans with salt-sensitive and salt-resistant blood pressure.

Recent studies demonstrate that high dietary sodium (HS) impairs endothelial function in those with salt-resistant (SR) blood pressure (BP). The effect of HS on endothelial function in those with salt-sensitive (SS) BP is not currently known. We hypothesized that HS would impair brachial artery flow-mediated dilation (FMD) to a greater extent in SS compared with SR adults. Ten SR (age 42 ± 5 yr, 5 men, 5 women) and 10 SS (age 39 ± 5 yr, 5 men, 5 women) healthy, normotensive participants were enrolled in a controlled feeding study consisting of a run-in diet followed by a 7-day low dietary sodium (LS) (20 mmol/day) and a 7-day HS (300 mmol/day) diet in random order. Brachial artery FMD and 24-h BP were assessed on the last day of each diet. SS BP was individually assessed and defined as a change in 24-h mean arterial pressure (MAP) of >5 mmHg between the LS and HS diets (ΔMAP: SR -0.6 ± 1.2, SS 7.7 ± 0.4 mmHg). Brachial artery FMD was lower in both SS and SR individuals during the HS diet (P < 0.001), and did not differ between groups (P > 0.05) (FMD: SR LS 10.6 ± 1.3%, SR HS 7.2 ± 1.5%, SS LS 12.5 ± 1.7%, SS HS 7.8 ± 1.4%). These data indicate that an HS diet impairs brachial artery FMD to a similar extent in adults with SS BP and SR BP.

Acute impact of retrograde shear rate on brachial and superficial femoral artery flow-mediated dilation in humans.

Retrograde shear rate (SR) in the brachial artery (BA) is associated with endothelial dysfunction; a precursor to atherosclerosis. The BA does not typically manifest clinical atherosclerosis, whereas the superficial femoral artery (SFA) is more prone to developing plaque. Examine whether the impact of incremental levels of retrograde SR differs between atherosclerosis‐prone (i.e., SFA) and ‐resistant vessels (i.e., BA) in healthy men. Thirteen healthy young men reported three times to the laboratory. We examined BA flow‐mediated dilation (FMD) before and after 30‐min exposure to cuff inflation around the forearm at 0, 30, and 60 mmHg, to manipulate retrograde SR. Subsequently, the 30‐min intervention was repeated in the SFA, using the same cuff pressure as in the forearm. Order of testing (vessel and intervention) was randomized among subjects. We found a dose‐dependent increase in retrograde SR with 30 and 60 mmHg cuff inflation, which was present in both the BA and SFA (all P < 0.05). BA and SFA FMD decreased after the 30‐min intervention (“time”: P = 0.012), and this was dependent on cuff pressure (“cuff × time”: P = 0.024). A significant decrease in FMD was observed after 60 mmHg only and this change was similarly present in both arteries (“time × artery”: P = 0.227). Moreover, the BA and SFA demonstrate a similar relationship between changes in retrograde SR and FMD (r = 0.498 and 0.475, respectively). Our study demonstrates that acute exposure to an increase in retrograde shear leads to comparable decreases in FMD in atherosclerotic‐prone and ‐resistant conduit arteries in humans.

Enhanced external counterpulsation creates acute blood flow patterns responsible for improved flow-mediated dilation in humans

Enhanced external counterpulsation (EECP) is a FDA-approved treatment for patients with coronary artery disease and unstable angina. Although beneficial effects of EECP have been linked to central/cardiac adaptations, recent findings have shown peripheral/vascular effects. Here, we sought to determine EECP-induced blood flow patterns and their association with vascular function. The present study was designed to investigate endothelium-mediated arterial vasodilation changes after one 45-min session of either EECP or Sham EECP in 18 randomly assigned apparently healthy, young men (25±4 years). Brachial (b) and femoral (f) flow-mediated dilation (FMD) were assessed before and within 10 min after completing EECP or Sham. After 20 min of EECP, peak blood flow velocity (V) and brachial and femoral artery diameters (D) were recorded live for 2 min. In addition, a blood sample was drawn from the earlobe to determine hematocrit and then to calculate blood viscosity (μ) and density (ρ), Reynolds number (Re=V*D*ρ/μ), and endothelial shear stress (ESS=2μ*V/D). EECP increased retrograde shear stress and retrograde-turbulent blood flow in the femoral artery and antegrade-laminar shear stress in the brachial artery. fFMD was increased after EECP compared with Sham and baseline (fFMD=13.1±3.7 vs. 7.9±4.6% and 7.8±4.5%, respectively, P<0.05) and bFMD was increased after EECP compared with baseline (bFMD=10.6±4.8 vs. 7.0±3.5%, P<0.05), despite different blood flow patterns. These results provide novel evidence that a single session of EECP-induced blood flow patterns improve endothelial function in peripheral muscular conduit arteries.

Parameters of blood viscosity do not correlate with the extent of coronary and carotid atherosclerosis and with endothelial function in patients undergoing coronary angiography

While the role of physical forces on the control of atherogenesis and the modulation of endothelial function is well known, studies investigating the impact of shear stress on the extent of central atherosclerosis and flow-mediated dilation in humans produced controversial results. We investigated the relationship between viscosity, coronary atherosclerosis, carotid intima-media thickness and flow-mediated dilation in patients undergoing coronary angiography. 451 patients (306 males, mean age 66 ± 10) were enrolled. Viscosity, which was calculated using a validated formula, showed a positive association with platelet activation (P = 0.01), leukocyte counts (P = 0.006) and C-reactive protein (P = 0.03), a marker of inflammation; surprisingly, visocsity showed a negative association with FMD (FMD decreased 0.14 ± 0.05% per each cPoise increase in viscosity) but only in patients without coronary artery disease. Viscosity showed no association with the extent of coronary or carotid artery disease. We provide cross-sectional data on the relationship between whole blood viscosity and parameters of vascular structure and function. While viscosity correlated with parameters of vascular inflammation, it showed no relationship with the presence and severity of central atherosclerosis.

α1-Adrenoreceptor activity does not explain lower morning endothelial-dependent, flow-mediated dilation in humans

Early morning reduction in endothelium-dependent, flow-mediated dilation (FMD) may contribute to the high incidence of sudden cardiac death at this time of day. The mechanisms underpinning diurnal variation in FMD are unclear, but potentially relate to a circadian rhythm in sympathetic nerve activity. We hypothesized that blockade of α(1)-mediated sympathetic nerve activity would act to attenuate the diurnal variation in FMD. In a randomized and placebo-controlled design, we measured brachial artery FMD in 12 participants (mean age = 26 yr, SD = 3) at 0600 and 1600 after ingestion of an α(1)-blocker (prazosin, 1 mg/20 kg body mass) or placebo. Arterial diameter and shear rate were assessed using edge-detection software. Heart rate and blood pressure were also measured. Data were analyzed using linear mixed modeling. Following placebo, FMD was 8 ± 2% in the morning compared with 10 ± 3% in the afternoon (P = 0.04). Blockade with prazosin led to a slight but nonsignificant increase in morning FMD (P = 0.24) and a significant (P = 0.04) decrease in afternoon FMD, resulting in no diurnal variation (P = 0.20). Shear rate did not differ in the morning or afternoon under either condition (P > 0.23). Blood pressure was lower following prazosin compared with placebo (P < 0.02), an effect that was similar at both times of day (P > 0.34). Heart rate and norepinephrine levels were higher in the afternoon following prazosin. These data indicate that α(1)-adrenoreceptor activity does not explain lower morning endothelium-dependent FMD.

Reply to “Letter to the editor: ‘Assessment of flow-mediated dilation in humans: a methodological and physiological guideline'”

reply: We would like to thank Mc Loughlin and Mc Loughlin (4a) for their response and for bringing attention to the appropriate selection of transducer operating frequency for flow-mediated dilation investigations. We agree that employing a transducer with a higher central frequency (i.e., 12 MHz) will yield a greater detail resolution in the axial plane when interrogating vessels such as the brachial artery, and this would provide a greater sensitivity in detecting small changes in flow-evoked vasodilatation. However, in our review (8), we discussed not only the brachial artery but also the common femoral (9), profunda femoris (12), superficial femoral (1, 2, 10, 12), popliteal (5, 6, 11), and posterior tibial (3, 7) arteries. When these lower-limb vessels are insonated at an optimal region in terms of flow conditions, for example, at a distance where entrance effects are minimized, the artery depth is often greater than that expected for a typical brachial artery. Given that the average attenuation coefficient is 0.5 dB·cm−1·MHz−1 (4), there is considerable degradation of image quality when employing a high-frequency probe while imaging a deeper lying vessel. This can render the image unusable when combined with automated analysis software. The subsequent trade-off between detail resolution and depth penetration is a further consideration for researchers when performing flow-mediated dilation investigations; however, the minimum transducer recommended is 7.5 MHz for all peripheral arteries so as to maintain adequate detail resolution. Certainly, we advocate the use of higher transducer frequencies (i.e., 12 MHz) when investigating more superficial vessels such as the brachial and radial arteries.

Assessment of flow-mediated dilation in humans: a methodological and physiological guideline

Endothelial dysfunction is now considered an important early event in the development of atherosclerosis, which precedes gross morphological signs and clinical symptoms. The assessment of flow-mediated dilation (FMD) was introduced almost 20 years ago as a noninvasive approach to examine vasodilator function in vivo. FMD is widely believed to reflect endothelium-dependent and largely nitric oxide-mediated arterial function and has been used as a surrogate marker of vascular health. This noninvasive technique has been used to compare groups of subjects and to evaluate the impact of interventions within individuals. Despite its widespread adoption, there is considerable variability between studies with respect to the protocols applied, methods of analysis, and interpretation of results. Moreover, differences in methodological approaches have important impacts on the response magnitude, can result in spurious data interpretation, and limit the comparability of outcomes between studies. This review results from a collegial discussion between physiologists with the purpose of developing considered guidelines. The contributors represent several distinct research groups that have independently worked to advance the evidence base for improvement of the technical approaches to FMD measurement and analysis. The outcome is a series of recommendations on the basis of review and critical appraisal of recent physiological studies, pertaining to the most appropriate methods to assess FMD in humans.

Should we be on the fence or can we open the gate? Evidence that QRS gating in FMD analysis is not essential

the function of arterial endothelial cells is now recognized as an important factor in the pathogenesis of atherosclerosis. Almost two decades ago, Celermajer and colleagues ([2][1]) introduced a noninvasive assessment technique to evaluate endothelial function in humans. In this test, the magnitude

Intermittent exercise abolishes the diurnal variation in endothelial-dependent flow-mediated dilation in humans

It is currently unclear to what extent diurnal variation and exercise effect endothelium-dependent nitric oxide (NO)-mediated vasodilation. Therefore, we measured brachial artery flow-mediated dilation (FMD) in 10 males (mean age = 28 yr, SD = 7), before and after a bout of intermittent cycling at 70% peak oxygen uptake on separate days beginning either at 0800 or 1600. Edge-detection and wall-tracking software was used to measure changes in arterial diameter, while shear rate (SR) was assessed using simultaneously derived blood flow velocity and B-mode diameter data. The FMD data were analyzed before and after normalization for SR with repeated-measures models. Before exercise, mean + or - SD FMD was 7 + or - 3% in the morning compared with 11 + or - 6% in the afternoon (P = 0.01). This diurnal variation persisted after data were normalized for SR, which was found to be unaffected by time of day (P = 0.33). Postexercise SR was higher than at baseline (pre-exercise) (P = 0.01) to a similar extent at both times of day. FMD was unaffected by exercise in the morning (P = 0.96) but decreased by 4 + or - 3% following exercise in the afternoon (P = 0.01) so that postexercise measurements did not differ between times of day. These data indicate that endothelium-dependent FMD is lower in the morning, and this finding was not altered by normalization of FMD for diurnal variation in SR. This infers a reduced function of the intrinsic endothelial NO-vasodilator system in the morning. We also report, for the first time, that a bout of intermittent exercise abolishes this diurnal variation in endothelium-dependent FMD.

Effects of a low-salt diet on flow-mediated dilatation in humans

Background:The effect of salt reduction on vascular function, assessed by brachial artery flow-mediated dilatation (FMD), is unknown.Objective: Our aim was to compare the effects of a low-salt (LS; 50 mmol Na/d) diet with those of a usual-salt (US; 150 mmol Na/d) diet on FMD.Design: This was a randomized crossover design in which 29 overweight and obese normotensive men and women followed an LS diet and a US diet for 2 wk. Both diets had similar potassium and saturated fat contents and were designed to ensure weight stability. After each intervention, FMD, pulse wave velocity, augmentation index, and blood pressure were measured.Results: FMD was significantly greater (P = 0.001) with the LS diet (4.89 ± 2.42%) than with the US diet (3.37 ± 2.10%), systolic blood pressure was significantly (P = 0.02) lower with the LS diet (112 ± 11 mm Hg) than with the US diet (117 ± 13 mm Hg), and 24-h sodium excretion was significantly lower (P = 0.0001) with the LS diet (64.1 ± 41.3 mmol) than with the US diet (156.3 ± 56.7 mmol). There was no correlation between change in FMD and change in 24-h sodium excretion or change in blood pressure. No significant changes in augmentation index or pulse wave velocity were observed.Conclusions: Salt reduction improves endothelium-dependant vasodilation in normotensive subjects independently of the changes in measured resting clinic blood pressure. These findings suggest additional cardioprotective effects of salt reduction beyond blood pressure reduction. The trial is registered with the Australian and New Zealand Clinical Trials Registry (unique identifier: ANZCTR12607000381482; >http://www.anzctr.org.au/trial_view.aspx?ID=82159).

Importance of Measuring the Time Course of Flow-Mediated Dilatation in Humans

Flow-mediated dilatation (FMD) is widely used to describe conduit artery endothelial function. The traditional approaches to FMD calculation assess diameter change at arbitrary time points after occluding cuff deflation. The aim of this study was to examine the time course of brachial artery FMD after a 5-minute period of forearm ischemia in 12 young, 12 fitness matched older and 12 older untrained subjects. Edge-detection and wall tracking of high resolution B-mode arterial ultrasound images, combined with synchronized Doppler waveform envelope analysis, were used to calculate brachial artery diameter, blood flow, and shear rate continuously across the cardiac cycle after forearm ischemia. FMD was significantly higher in young healthy subjects (7.8+/-3.2%) compared with sedentary older subjects (5.2+/-2.8%, P<0.05) but not trained older subjects (6.4+/-2.3%). Time to peak diameter differed between young (50+/-11 seconds) and both older groups (trained; 80+/-21, P<0.001; sedentary: 83+/-36 seconds, P<0.001). A large proportion (>42%) of true peak diameters fell outside the time frames typically used to assess FMD in the literature. When calculated according to the commonly used approach, ie, 60 s after cuff deflation, FMD was significantly lower compared with true peak FMD in all groups (P<0.001), and no differences were evident between the groups. The time course of FMD differs significantly between young and older subjects. Studies assuming that peak dilation occurs at an arbitrary time point, or within limited time windows, may draw misleading conclusions regarding differences between groups. More sophisticated approaches to measurement of FMD are required if it is to be considered a valid biomarker of vascular disease.

Cytochrome P450 2C9 is involved in flow‐dependent vasodilation of peripheral conduit arteries in healthy subjects and in patients with chronic heart failure

Flow-mediated dilation (FMD) of human conduit arteries is, in part, related to shear stress-induced release of endothelium-derived nitric oxide (NO). However, NO synthase inhibitors do not completely abolish this FMD-response. Recently, a cytochrome P450 (CYP) epoxygenase of the 2C family was linked to NO- and prostacyclin-independent relaxation of conduit arteries. We therefore evaluated the contribution of CYP 2C9 to FMD in humans. FMD of the radial artery was determined in 12 healthy volunteers by high-resolution ultrasound and analyzed before and after intra-arterial infusion of sulfaphenazole, a specific CYP 2C9 inhibitor, L-NMMA (NO synthase inhibitor) and co-infusion of both. Endothelium-independent vasodilation was characterized after intra-arterial infusion of SNP. FMD was reduced after sulfaphenazole (11.5+/-0.87% vs. 7.4+/-0.95%, p<0.01), after L-NMMA (6.0+/-0.71%; p<0.01), and after co-infusion 3.9+/-0.73% (p<0.05 vs. L-NMMA; p<0.01 vs. sulfaphenazole). Sulfaphenazole had no effect on endothelium-independent vasodilation. In patients with chronic heart failure, the portion of FMD blocked by sulfaphenazole was not affected. CYP 2C was detected by immunohistochemistry in radial artery samples obtained from patients undergoing coronary bypass surgery. FMD in human conductance arteries is reduced after inhibition of CYP 2C9, supporting the concept that CYP 2C metabolites contribute to endothelium-mediated vasodilation of peripheral conduit arteries in vivo. In patients with heart failure, the CYP-dependent FMD appears to be preserved.

Crucial Role of NO and Endothelium-Derived Hyperpolarizing Factor in Human Sustained Conduit Artery Flow-Mediated Dilatation

Whether NO is involved or not in sustained conduit artery flow-mediated dilatation in humans remains unclear. Moreover, the role of endothelium-derived hyperpolarizing factor (EDHF), synthesized by cytochrome epoxygenases and acting through calcium-activated potassium channels, and its relationship with NO during flow-mediated dilatation have never been investigated previously. In 12 healthy subjects we measured radial artery diameter (echotracking) and blood flow (Doppler) during flow-mediated dilatation induced by gradual distal hand skin heating (34 to 44 degrees C), during the local infusion of saline and inhibitors of NO synthase (N(G)-monomethyl-l-arginine [l-NMMA]: 8 to 20 micromol/min per liter), calcium-activated potassium channels (tetraethylammonium chloride: 9 micromol/min per liter), and cytochrome epoxygenases (fluconazole: 0.4 to 1.6 micromol/min per liter), alone and in combination. Mean wall shear stress, the flow-mediated dilatation stimulus, was calculated at each level of flow, and the diameter-wall shear stress relationship was constructed. During heating, compared with saline, the diameter-shear stress relationship was shifted downward by l-NMMA, tetraethylammonium, fluconazole, and, in a more pronounced manner, by the combinations of l-NMMA with tetraethylammonium or with fluconazole. Therefore, maximal radial artery flow-mediated dilatation, compared with saline (0.62+/-0.03 mm), was decreased under our experimental conditions by l-NMMA (-39+/-4%), tetraethylammonium chloride (-14+/-4%), fluconazole (-18+/-6%), and to a greater extent, by the combinations of l-NMMA with tetraethylammonium (-64+/-4%) or with fluconazole (-71+/-3%). This study demonstrates that NO and a cytochrome-related EDHF are involved in peripheral conduit artery flow-mediated dilatation in humans during sustained flow conditions. Moreover, the synergistic effects of the inhibitors strongly suggest a functional interaction between NO and EDHF pathways.

Addition of milk prevents vascular protective effects of tea

Experimental and clinical studies indicate that tea exerts protection against cardiovascular diseases. However, a question of much debate is whether addition of milk modifies the biological activities of tea. We studied the vascular effects of tea, with or without milk, in humans and elucidated the impact of individual milk proteins in cell culture experiments, with isolated rat aortic rings and by HPLC analysis. A total of 16 healthy female volunteers consumed either 500 mL of freshly brewed black tea, black tea with 10% skimmed milk, or boiled water as control. Flow-mediated dilation (FMD) was measured by high-resolution vascular ultrasound before and 2 h after consumption. Black tea significantly improved FMD in humans compared with water, whereas addition of milk completely blunted the effects of tea. To support these findings, similar experiments were performed in isolated rat aortic rings and endothelial cells. Tea induced vasorelaxation in rat aortic rings and increased the activity of endothelial nitric oxide synthase by phosphorylation of the enzyme in endothelial cells. All effects were completely inhibited by the addition of milk to tea. Of the various kinds of milk proteins, the caseins accounted for these inhibiting effects of milk, probably by formation of complexes with tea catechins. Milk counteracts the favourable health effects of tea on vascular function. This finding indicates the need for particular awareness in the interpretation and design of studies comprising nutritional flavonoids.

Counterpoint: Flow-mediated dilation does not reflect nitric oxide-mediated endothelial function

The phenomenon of flow-mediated dilation (FMD) relevant to this debate describes the vasodilation in a conduit vessel in response to elevations in flow-associated shear stress. Nitric oxide (NO) is thought to play a key role in vascular health due to its established vasoprotective characteristics (

Flow-mediated and reflex changes in large peripheral artery tone in humans.

Studies of peripheral blood vessels in humans have focused primarily on regulation of blood flow and vascular resistance, which are thought to reflect small vessel caliber. Recent studies in animals have identified flow-mediated and neurogenic changes in large artery diameter. This study tested for flow-mediated dilatation and reflex constriction of the brachial artery in humans. A dual-crystal pulsed Doppler system was used to measure brachial artery diameter and blood flow proximal to the antecubital fossa. To test for flow-mediated dilatation, flow through the brachial artery was altered by an occluding cuff placed on the forearm distal to the site of brachial artery flow and diameter measurement. Control blood flow was 123 +/- 20 ml/min, and brachial artery diameter was 4.74 +/- 0.17 mm (mean +/- SEM). By inflating the distal occluding cuff (distal circulatory arrest), flow was reduced through the brachial artery to 21 +/- 5 ml/min (p less than 0.005), and brachial artery diameter was reduced to 4.35 +/- 0.20 mm (p less than 0.001). By deflating the distal occluding cuff after 10 minutes (reactive hyperemia), brachial artery flow was increased to 358 +/- 55 ml/min (p less than 0.001), and diameter was increased to 5.6 +/- 0.19 mm (p less than 0.001). These interventions did not change systemic arterial pressure and, as measured in three subjects, caused only small changes in local brachial artery distending pressure. Thus, both increased and decreased brachial artery blood flow produced significant changes in brachial artery diameter without altering arterial distending pressure. These data provide evidence for flow-mediated dilatation in humans.(ABSTRACT TRUNCATED AT 250 WORDS)