The impact of an acute oral phosphate load on endothelium dependent and independent brachial artery vasodilation in healthy males

Serum phosphate levels are associated with cardiovascular morbidity and mortality in the general population and endothelial dysfunction may be mechanistically involved. The purpose of this study was to investigate the effects of acute phosphate supplementation on endothelial-dependent (flow-mediated dilation; FMD) and -independent (glyceryl trinitrate; GTN)) vasodilation in young, healthy males. Seventeen healthy male participants (age, 23 ± 3 years) were exposed to an oral load of phosphate (PHOS; liquid supplement containing 1200 mg of phosphorous) and placebo (PLAC) over 2 experimental days. A brachial artery FMD test was performed pre-ingestion and at 20 min, 60 min, and 120 min following the ingestion of the phosphate load or the placebo. GTN tests were performed pre- and 140 min post-ingestion. Serum phosphate was not impacted differently by phosphate versus placebo ingestion (p = 0.780). In contrast, urinary phosphate excretion was markedly increased in the PHOS (p < 0.001) but not in the PLAC condition (p = 0.130) (Δ fractional excretion of phosphate in PHOS (29.2%) vs. PLAC (9.3%)). This indicates that circulating phosphate levels were homeostatically regulated. GTN-mediated vasodilation was not significantly affected by phosphate ingestion. In primary analysis no impact of phosphate ingestion on FMD was detected. However, when the shear stress stimulus was added as a covariate in a subset of participants, exploratory pairwise comparisons revealed a significantly lower FMD 20 min post-phosphate ingestion versus placebo (p = 0.024). The effects of phosphate ingestion on FMD and serum phosphate are in contrast with previous findings and the mechanisms that underlie the disparate results require further investigation.

Download Full-text

Impact of controlling shear rate on flow-mediated dilation responses in the brachial artery of humans

Journal of Applied Physiology ◽

10.1152/japplphysiol.01245.2003 ◽

2004 ◽

Vol 97 (2) ◽

pp. 499-508 ◽

Cited By ~ 179

Author(s):

Kyra E. Pyke ◽

Erin M. Dwyer ◽

Michael E. Tschakovsky

Keyword(s):

Shear Stress ◽

Shear Rate ◽

Brachial Artery ◽

Reactive Hyperemia ◽

Flow Mediated Dilation ◽

Response Peak ◽

Dependent Flow ◽

Flow Mediated Vasodilation ◽

The Impact ◽

Forearm Occlusion

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.

Download Full-text

Can we IMPROVE cardiovascular outcomes through phosphate lowering in CKD? Rationale and protocol for the IMpact of Phosphate Reduction On Vascular End-points in Chronic Kidney Disease (IMPROVE-CKD) study

BMJ Open ◽

10.1136/bmjopen-2018-024382 ◽

2019 ◽

Vol 9 (2) ◽

pp. e024382 ◽

Cited By ~ 8

Author(s):

Nicole Lioufas ◽

Nigel D Toussaint ◽

Eugenia Pedagogos ◽

Grahame Elder ◽

Sunil V Badve ◽

...

Keyword(s):

Cardiovascular Disease ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Arterial Compliance ◽

Left Ventricular ◽

Serum Phosphate ◽

Lanthanum Carbonate ◽

Cardiovascular Morbidity And Mortality ◽

Fgf 23 ◽

The Impact

IntroductionPatients with chronic kidney disease (CKD) are at heightened cardiovascular risk, which has been associated with abnormalities of bone and mineral metabolism. A deeper understanding of these abnormalities should facilitate improved treatment strategies and patient-level outcomes, but at present there are few large, randomised controlled clinical trials to guide management. Positive associations between serum phosphate and fibroblast growth factor 23 (FGF-23) and cardiovascular morbidity and mortality in both the general and CKD populations have resulted in clinical guidelines suggesting that serum phosphate be targeted towards the normal range, although few randomised and placebo-controlled studies have addressed clinical outcomes using interventions to improve phosphate control. Early preventive measures to reduce the development and progression of vascular calcification, left ventricular hypertrophy and arterial stiffness are crucial in patients with CKD.Methods and analysisWe outline the rationale and protocol for an international, multicentre, randomised parallel-group trial assessing the impact of the non-calcium-based phosphate binder, lanthanum carbonate, compared with placebo on surrogate markers of cardiovascular disease in a predialysis CKD population—the IMpact of Phosphate Reduction On Vascular End-points (IMPROVE)-CKD study. The primary objective of the IMPROVE-CKD study is to determine if the use of lanthanum carbonate reduces the burden of cardiovascular disease in patients with CKD stages 3b and 4 when compared with placebo. The primary end-point of the study is change in arterial compliance measured by pulse wave velocity over a 96-week period. Secondary outcomes include change in aortic calcification and biochemical parameters of serum phosphate, parathyroid hormone and FGF-23 levels.Ethics and disseminationEthical approval for the IMPROVE-CKD trial was obtained by each local Institutional Ethics Committee for all 17 participating sites in Australia, New Zealand and Malaysia prior to study commencement. Results of this clinical trial will be published in peer-reviewed journals and presented at conferences.Trial registration numberACTRN12610000650099.

Download Full-text

Impaired brachial artery endothelium dependent flow mediated dilation in systemic lupus erythematosus: preliminary observations

Lupus ◽

10.1191/0961203304lu1072oa ◽

2004 ◽

Vol 13 (8) ◽

pp. 590-593 ◽

Cited By ~ 35

Author(s):

S R Johnson ◽

P J Harvey ◽

J S Floras ◽

M Iwanochko ◽

D Ibanez ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Brachial Artery ◽

Lupus Erythematosus ◽

Flow Mediated Dilation ◽

Systemic Lupus ◽

Dependent Flow

Download Full-text

The impact of a cold pressor test on brachial artery handgrip exercise-induced flow-mediated dilation

Vascular Medicine ◽

10.1177/1358863x15586473 ◽

2015 ◽

Vol 20 (5) ◽

pp. 409-416 ◽

Cited By ~ 4

Author(s):

Troy JR Stuckless ◽

Kyra E Pyke

Keyword(s):

Brachial Artery ◽

Cold Pressor Test ◽

Cold Pressor ◽

Flow Mediated Dilation ◽

Handgrip Exercise ◽

Pressor Test ◽

Induced Flow ◽

Exercise Induced ◽

The Impact

Download Full-text

Acute psychological and physical stress transiently enhances brachial artery flow-mediated dilation stimulated by exercise-induced increases in shear stress

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2013-0384 ◽

2014 ◽

Vol 39 (8) ◽

pp. 927-936 ◽

Cited By ~ 9

Author(s):

Ingrid C. Szijgyarto ◽

Veronica J. Poitras ◽

Brendon J. Gurd ◽

Kyra E. Pyke

Keyword(s):

Shear Stress ◽

Shear Rate ◽

Brachial Artery ◽

Stress Responses ◽

Physical Stress ◽

Flow Mediated Dilation ◽

Trial Effect ◽

Condition Effect ◽

Exercise Induced ◽

The Impact

Exercise elevates conduit artery shear stress and stimulates flow-mediated dilation (FMD). However, little is known regarding the impact of acute psychological and physical stress on this response. The purpose of this study was to examine the impact of the Trier Social Stress Test (TSST (speech and arithmetic tasks)) and a cold pressor test (CPT) with and without social evaluation (SE) on exercise-induced brachial artery FMD (EX-FMD). A total of 59 healthy male subjects were randomly assigned to 1 of 3 conditions: TSST, CPT, or CPT with SE. During 6 min of handgrip exercise, brachial artery EX-FMD was assessed before and 15 and 35 min poststress with echo and Doppler ultrasound. Shear stress was estimated as shear rate, calculated as brachial artery mean blood velocity/brachial artery diameter. Results are means ± SD. All conditions elicited significant physiological stress responses. Salivary cortisol increased from 4.6 ± 2.4 nmol/L to 10.0 ± 5.0 nmol/L (p < 0.001; condition effect: p = 0.292). Mean arterial pressure increased from 98.6 ± 12.1 mm Hg to 131.9 ± 18.7 mm Hg (p < 0.001; condition effect: p = 0.664). Exercise shear rate did not differ between conditions (p = 0.592), although it was modestly lower poststress (prestress: 72.3 ± 4.5 s−1; 15 min poststress: 70.8 ± 5.4 s−1; 35 min poststress: 70.6 ± 6.1 s−1; trial effect: p = 0.011). EX-FMD increased from prestress to 15 min poststress in all conditions (prestress: 6.2% ± 2.8%; 15 min poststress: 7.9% ± 3.2%; 35 min poststress: 6.6% ± 2.9%; trial effect: p < 0.001; condition effect: p = 0.611). In conclusion, all conditions elicited similar stress responses that transiently enhanced EX-FMD. This response may help to support muscle perfusion during stress.

Download Full-text

Arteriovenous fistula and pre-surgery mapping: Potential role of physical exercise on endothelial function

The Journal of Vascular Access ◽

10.1177/1129729819838180 ◽

2019 ◽

Vol 20 (6) ◽

pp. 652-658 ◽

Cited By ~ 1

Author(s):

Giulio Distefano ◽

Luca Zanoli ◽

Antonio Basile ◽

Pasquale Fatuzzo ◽

Antonio Granata

Keyword(s):

Physical Exercise ◽

Endothelial Function ◽

Arteriovenous Fistula ◽

Radial Artery ◽

Upper Limb ◽

Brachial Artery ◽

Resistance Index ◽

Resistive Index ◽

Flow Mediated Dilation ◽

The Impact

Background: The success of the construction of an arteriovenous fistula for haemodialysis is related to the vascular function of the vessels involved in the anastomosis, with particular reference to radial artery distensibility after reactive hyperaemia test and to the fall of resistance index. Only few studies have evaluated the impact of exercise protocols on the endothelial and morphological characteristics of the vessels of the upper limb with inconclusive results. In this pilot longitudinal study, we aimed to evaluate the impact of a standardized exercise protocol on the haemodynamic and resistive index of the arteries of the upper limb of uraemic patients. Methods: A total of 17 uraemic patients planned to construct arteriovenous fistula at the distal third of the forearm were enrolled and followed up for 30 days. All patients performed repeated handgrips for 30 min/day. The arterial parameters were detected before and after an ischaemic stress of 5 min and radial and brachial artery flow-mediated dilation was evaluated as well as radial artery resistance index. Results: Pre-exercise measurements of radial artery diameter and resistance index and brachial artery diameter were not modified by 30 days hand physical exercise, whereas the post-exercise haemodynamic were improved. Consequently, flow-mediated dilation of the radial artery was improved (21% ± 14% vs 30% ± 19%; p = 0.03) and resistance index of the radial artery was reduced ( p = 0.02). Conclusion: Exercise has beneficial effects on endothelial function of the radial artery by resistive index and, potentially, on the outcome of the arteriovenous fistula. Further studies with larger sample size are needed to confirm our preliminary data.

Download Full-text

ASARM peptides: PHEX-dependent and -independent regulation of serum phosphate

AJP Renal Physiology ◽

10.1152/ajprenal.00304.2010 ◽

2011 ◽

Vol 300 (3) ◽

pp. F783-F791 ◽

Cited By ~ 34

Author(s):

Valentin David ◽

Aline Martin ◽

Anne-Marie Hedge ◽

Marc K. Drezner ◽

Peter S. N. Rowe

Keyword(s):

Vitamin D ◽

Fibroblast Growth Factor 23 ◽

Inverse Correlation ◽

Fractional Excretion ◽

Serum Phosphate ◽

Hypophosphatemic Rickets ◽

Separate Experiment ◽

Constitutive Overexpression ◽

Fractional Excretion Of Phosphate

Increased acidic serine aspartate-rich MEPE-associated motif (ASARM) peptides cause mineralization defects in X-linked hypophosphatemic rickets mice (HYP) and “directly” inhibit renal phosphate uptake in vitro. However, ASARM peptides also bind to phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX) and are a physiological substrate for this bone-expressed, phosphate-regulating enzyme. We therefore tested the hypothesis that circulating ASARM peptides also “indirectly” contribute to a bone-renal PHEX-dependent hypophosphatemia in normal mice. Male mice ( n = 5; 12 wk) were fed for 8 wk with a normal phosphorus and vitamin D3 diet (1% Pi diet) or a reduced phosphorus and vitamin D3 diet (0.1% Pi diet). For the final 4 wk, transplantation of mini-osmotic pumps supplied a continuous infusion of either ASARM peptide (5 mg·day−1·kg−1) or vehicle. HYP, autosomal recessive hypophosphatemic rickets (ARHR), and normal mice (no pumps or ASARM infusion; 0.4% Pi diet) were used in a separate experiment designed to measure and compare circulating ASARM peptides in disease and health. ASARM treatment decreased serum phosphate concentration and renal phosphate cotransporter (NPT2A) mRNA with the 1% Pi diet. This was accompanied by a twofold increase in serum ASARM and 1,25-dihydroxy vitamin D3 [1,25 (OH)2D3] levels without changes in parathyroid hormone. For both diets, ASARM-treated mice showed significant increases in serum fibroblast growth factor 23 (FGF23; +50%) and reduced serum osteocalcin (−30%) and osteopontin (−25%). Circulating ASARM peptides showed a significant inverse correlation with serum Pi and a significant positive correlation with fractional excretion of phosphate. We conclude that constitutive overexpression of ASARM peptides plays a “component” PHEX-independent part in the HYP and ARHR hypophosphatemia. In contrast, with wild-type mice, ASARM peptides likely play a bone PHEX-dependent role in renal phosphate regulation and FGF23 expression. They may also coordinate FGF23 expression by competitively modulating PHEX/DMP1 interactions and thus bone-renal mineral regulation.

Download Full-text

The impact of acute mental stress on brachial artery flow-mediated dilation differs when shear stress is elevated by reactive hyperemia versus handgrip exercise

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2012-0328 ◽

2013 ◽

Vol 38 (5) ◽

pp. 498-506 ◽

Cited By ~ 16

Author(s):

Ingrid C. Szijgyarto ◽

Trevor J. King ◽

Jennifer Ku ◽

Veronica J. Poitras ◽

Brendon J. Gurd ◽

...

Keyword(s):

Shear Stress ◽

Brachial Artery ◽

Mental Stress ◽

Stress Reactivity ◽

Reactive Hyperemia ◽

Blood Velocity ◽

Flow Mediated Dilation ◽

Handgrip Exercise ◽

Stress Task ◽

The Impact

Acute mental stress can impair brachial artery (BA) flow-mediated dilation (FMD) in response to reactive hyperemia (RH) induced increases in shear stress. Handgrip exercise (HGEX) is emerging as a useful tool to increase shear stress for FMD assessment; however, the impact of acute mental stress on HGEX-FMD is unknown. The purpose of this study was to determine whether acute mental stress attenuates RH- and HGEX-induced BA-FMD to a similar extent. In 2 counterbalanced visits, 16 healthy males (19–27 years of age) performed RH-FMD or HGEX-FMD tests after a counting control task (prestress FMD) and a speech and arithmetic stress task (poststress FMD). BA diameter and mean blood velocity were assessed with echo and Doppler ultrasound, respectively. Shear stress was estimated using shear rate (SR = BA blood velocity/BA diameter). Mean arterial pressure (MAP), heart rate (HR), and salivary cortisol were used to assess stress reactivity. Results are expressed as mean ± SE. The stress task elevated MAP (Δ24.0 ± 2.6 mm Hg) and HR (Δ15.5 ± 1.9 beats·min–1), but not cortisol (prestress vs. poststress: 4.4 ± 0.7 nmol·L–1 vs. 4.7 ± 0.7 nmol·L–1; p = 0.625). There was no difference between the pre- and poststress SR stimulus for RH (p = 0.115) or HGEX (p = 0.664). RH-FMD decreased from 5.2% ± 0.6% prestress to 4.1% ± 0.5% poststress (p = 0.071); however, stress did not attenuate HGEX-FMD (prestress vs. poststress: 4.1% ± 0.6% vs. 5.3% ± 0.6%; p = 0.154). The pre- to poststress change in FMD was significantly different in the RH-FMD vs. the HGEX-FMD test (–1.1% ± 0.6% vs. +1.1% ± 0.8%; p = 0.015). In conclusion, acute mental stress appears to have a disparate impact on FMD stimulated by RH vs. HGEX induced increases in shear stress.

Download Full-text