Skip to main content
SpringerLink
Log in

Impact of proximal and distal cuff inflation on brachial artery endothelial function in healthy individuals

  • Original Article
  • Published:
European Journal of Applied Physiology Aims and scope Submit manuscript

Abstract

Purpose

In this study, we examined whether the decrease in endothelial function associated with short-term exposure to elevated retrograde shear rate (SR), could be prevented when combined with a concurrent drop in transmural pressure in humans.

Methods

Twenty-five healthy individuals reported to our laboratory on three occasions to complete 30-min experimental conditions, preceded and followed by assessment of endothelial function using flow-mediated dilation (FMD). We used cuff inflation for 30-min to manipulate retrograde SR and transmural pressure in the brachial artery. Subjects underwent, in randomised order: (1) forearm cuff inflation to 60 mmHg (distal cuff; causing increase in retrograde SR), (2) upper arm cuff inflation to 60 mmHg (proximal cuff; causing increase in retrograde SR + decrease in transmural pressure), and (3) no cuff inflation (Control).

Results

The distal and proximal cuff conditions both increased brachial artery retrograde SR (p < 0.001) and oscillatory shear index (p < 0.001). The Control intervention did not alter SR patterns or FMD (p > 0.05). A significant interaction-effect was found for FMD (p < 0.05), with the decrease during distal cuff (from 6.9 ± 2.3% to 6.1 ± 2.5%), being reversed to an increase with proximal cuff (from 6.3 ± 2.0 to 6.9 ± 2.0%). The proximal cuff-related increase in FMD could not be explained by the decrease in antegrade or increase in retrograde shear.

Conclusion

This study suggests that a decrease in transmural pressure may ameliorate the decline in endothelial function that occurs following exposure to elevated retrograde shear in healthy individuals.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

ANOVA:

One-way analysis of variance

DBP:

Diastolic blood pressure

FMD:

Flow-mediated dilation

MAP:

Mean arterial pressure

NO:

Nitric oxide

OSI:

Oscillatory shear index

ROI:

Regions of interest

ROS:

Reactive oxygen species

SBP:

Systolic blood pressure

SR:

Shear rate

SRauc :

Shear rate area under the curve

TTP:

Time to peak

References

  • Abay T, Kyriacou P (2016) Comparison of NIRS, laser Doppler flowmetry, photoplethysmography, and pulse oximetry during vascular occlusion challenges. Physiol Meas 37:503

    Article  CAS  Google Scholar 

  • Agewall S, Whalley G, Doughty R, Sharpe N (1999) Handgrip exercise increases postocclusion hyperaemic brachial artery dilatation. Heart 82:93–95

    Article  CAS  Google Scholar 

  • Anderson W, Johnston C, Korner P (1979) Acute renal haemodynamic and renin-angiotensin system responses to graded renal artery stenosis in the dog. J Physiol 287:231–245

    Article  CAS  Google Scholar 

  • Atkinson G, Batterham AM, Thijssen DH, Green DJ (2013) A new approach to improve the specificity of flow-mediated dilation for indicating endothelial function in cardiovascular research. J Hypertens 31:287–291. https://doi.org/10.1097/HJH.0b013e32835b8164

    Article  CAS  PubMed  Google Scholar 

  • Atkinson CL et al (2015) Opposing effects of shear-mediated dilation and myogenic constriction on artery diameter in response to handgrip exercise in humans. J Appl Physiol 119:858–864

    Article  Google Scholar 

  • Bache RJ, Schwartz JS (1982) Effect of perfusion pressure distal to a coronary stenosis on transmural myocardial blood flow. Circulation 65:928–935

    Article  CAS  Google Scholar 

  • Behrendt D, Ganz P (2002) Endothelial function. From vascular biology to clinical applications. Am J Cardiol 90:40L-48L

    Article  CAS  Google Scholar 

  • Betik AC, Luckham VB, Hughson RL (2004) Flow-mediated dilation in human brachial artery after different circulatory occlusion conditions American Journal of Physiology-Heart and Circulatory. Physiology 286:H442–H448

    CAS  Google Scholar 

  • Black MA, Cable NT, Thijssen DH, Green DJ (2008) Importance of measuring the time course of flow-mediated dilatation in humans. Hypertension 51:203–210. https://doi.org/10.1161/HYPERTENSIONAHA.107.101014

    Article  CAS  PubMed  Google Scholar 

  • Chappell DC, Varner SE, Nerem RM, Medford RM, Alexander RW (1998) Oscillatory shear stress stimulates adhesion molecule expression in cultured human endothelium. Circ Res 82:532–539

    Article  CAS  Google Scholar 

  • Chatzizisis YS, Coskun AU, Jonas M, Edelman ER, Feldman CL, Stone PH (2007) Role of endothelial shear stress in the natural history of coronary atherosclerosis and vascular remodeling: molecular, cellular, and vascular behavior. J Am Coll Cardiol 49:2379–2393. https://doi.org/10.1016/j.jacc.2007.02.059

    Article  CAS  PubMed  Google Scholar 

  • Corretti MC et al (2002) Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol 39:257–265

    Article  Google Scholar 

  • De Keulenaer WG, Alexander RW, Ushio-Fukai M, Ishizaka N, Griendling KK (1998) Tumour necrosis factor α activates a p22phox-based NADH oxidase in vascular smooth muscle. Biochem J 329:653–657

    Article  Google Scholar 

  • de Leeuw PW, Postma CT, Spiering W, Kroon AA (2018) Atherosclerotic renal artery stenosis: should we intervene earlier? Curr Hypertens Rep 20:35

    Article  Google Scholar 

  • Dirksen MT, van der Wal AC, van den Berg FM, van der Loos CM, Becker AE (1998) Distribution of inflammatory cells in atherosclerotic plaques relates to the direction of flow. Circulation 98:2000–2003

    Article  CAS  Google Scholar 

  • Doshi SN, Naka KK, Payne N, Jones CJ, Ashton M, Lewis MJ, Goodfellow J (2001) Flow-mediated dilatation following wrist and upper arm occlusion in humans: the contribution of nitric oxide. Clin Sci 101:629–635

    Article  CAS  Google Scholar 

  • Ekelund U, Björnberg J, Grande PO, Albert U, Mellander S (1992) Myogenic vascular regulation in skeletal muscle in vivo is not dependent of endothelium-derived nitric oxide. Acta Physiol Scand 144:199–207

    Article  CAS  Google Scholar 

  • Glowinska-Olszewska B, Tolwinska J, Urban M (2007) Relationship between endothelial dysfunction, carotid artery intima media thickness and circulating markers of vascular inflammation in obese hypertensive children and adolescents. J Pediatr Endocrinol Metab 20:1125–1136

    Article  CAS  Google Scholar 

  • Green DJ, Jones H, Thijssen D, Cable N, Atkinson G (2011) Flow-mediated dilation and cardiovascular event prediction: does nitric oxide matter? Hypertension 57:363–369

    Article  CAS  Google Scholar 

  • Green DJ, Hopman MT, Padilla J, Laughlin MH, Thijssen DH (2017) Vascular adaptation to exercise in humans: role of hemodynamic stimuli. Physiol Rev 97:495–528

    Article  CAS  Google Scholar 

  • Halcox JP et al (2009) Endothelial function predicts progression of carotid intima-media thickness. Circulation 119:1005–1012

    Article  Google Scholar 

  • Himburg HA, Dowd SE, Friedman MH (2007) Frequency-dependent response of the vascular endothelium to pulsatile shear stress American Journal of Physiology-Heart and Circulatory. Physiology 293:H645–H653

    CAS  Google Scholar 

  • Holder SM, Dawson EA, Brislane A, Hisdal J, Green DJ, Thijssen DH (2019) Fluctuation in shear rate, with unaltered mean shear rate, improves brachial artery flow-mediated dilation in healthy, young men. J Appl Physiol 126:1687–1693

    Article  Google Scholar 

  • Hwang J et al (2003) Pulsatile versus oscillatory shear stress regulates NADPH oxidase subunit expression: implication for native LDL oxidation. Circ Res 93:1225–1232. https://doi.org/10.1161/01.RES.0000104087.29395.66

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Johnson BD, Mather KJ, Wallace JP (2011) Mechanotransduction of shear in the endothelium: basic studies and clinical implications. Vasc Med 16:365–377. https://doi.org/10.1177/1358863X11422109

    Article  PubMed  Google Scholar 

  • Jones H, Green DJ, George K, Atkinson G (2010) Intermittent exercise abolishes the diurnal variation in endothelial-dependent flow-mediated dilation in humans. Am J Physiol Regul Integr Comp Physiol 298:R427-432. https://doi.org/10.1152/ajpregu.00442.2009

    Article  CAS  PubMed  Google Scholar 

  • Juonala M, Viikari JS, Laitinen T, Marniemi J, Helenius H, Rönnemaa T, Raitakari OT (2004) Interrelations between brachial endothelial function and carotid intima-media thickness in young adults: the cardiovascular risk in young Finns study. Circulation 110:2918–2923

    Article  Google Scholar 

  • Kobayashi K, Akishita M, Yu W, Hashimoto M, Ohni M, Toba K (2004) Interrelationship between non-invasive measurements of atherosclerosis: flow-mediated dilation of brachial artery, carotid intima-media thickness and pulse wave velocity. Atherosclerosis 173:13–18

    Article  CAS  Google Scholar 

  • Koskinas KC, Chatzizisis YS, Baker AB, Edelman ER, Stone PH, Feldman CL (2009) The role of low endothelial shear stress in the conversion of atherosclerotic lesions from stable to unstable plaque. Curr Opin Cardiol 24:580–590. https://doi.org/10.1097/HCO.0b013e328331630b

    Article  PubMed  Google Scholar 

  • Ku DN (1997) Blood flow in arteries. Annu Rev Fluid Mech 29:399–434. https://doi.org/10.1146/annurev.fluid.29.1.399

    Article  Google Scholar 

  • Laughlin MH, Newcomer SC, Bender SB (2008) Importance of hemodynamic forces as signals for exercise-induced changes in endothelial cell phenotype. J Appl Physiol 104:588–600. https://doi.org/10.1152/japplphysiol.01096.2007

    Article  PubMed  Google Scholar 

  • Lee BY, Assadi C, Madden JL, Kavner D, Trainor FS, McCann WJ (1978) Hemodynamics of arterial stenosis. World J Surg 2:621–627

    Article  CAS  Google Scholar 

  • Lie M, Sejersted OM, Kiil F (1970) Local regulation of vascular cross section during changes in femoral arterial blood flow in dogs. Circ Res 27:727–737

    Article  CAS  Google Scholar 

  • McNally JS et al (2003) Role of xanthine oxidoreductase and NAD(P)H oxidase in endothelial superoxide production in response to oscillatory shear stress. Am J Physiol Heart Circ Physiol 285:H2290-2297. https://doi.org/10.1152/ajpheart.00515.2003

    Article  CAS  PubMed  Google Scholar 

  • Newcomer SC, Sauder CL, Kuipers NT, Laughlin MH, Ray CA (2008) Effects of posture on shear rates in human brachial and superficial femoral arteries. Am J Physiol Heart Circ Physiol 294:H1833-1839. https://doi.org/10.1152/ajpheart.01108.2007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Padilla J et al (2008) Normalization of flow-mediated dilation to shear stress area under the curve eliminates the impact of variable hyperemic stimulus. Cardiovasc Ultrasound 6:44. https://doi.org/10.1186/1476-7120-6-44

    Article  PubMed  PubMed Central  Google Scholar 

  • Schreuder TH, Green DJ, Hopman MT, Thijssen DH (2014) Acute impact of retrograde shear rate on brachial and superficial femoral artery flow-mediated dilation in humans. Physiol Rep 2:e00193. https://doi.org/10.1002/phy2.193

    Article  PubMed  PubMed Central  Google Scholar 

  • Simmons GH et al (2011) Increased brachial artery retrograde shear rate at exercise onset is abolished during prolonged cycling: role of thermoregulatory vasodilation. J Appl Physiol 110:389–397

    Article  Google Scholar 

  • Stegehuis VE, Wijntjens GW, Murai T, Piek JJ, van de Hoef TP (2018) Assessing the haemodynamic impact of coronary artery stenoses: intracoronary flow versus pressure measurements. Eur Cardiol Rev 13:46

    Article  Google Scholar 

  • Thijssen DH, Dawson EA, Tinken TM, Cable NT, Green DJ (2009) Retrograde flow and shear rate acutely impair endothelial function in humans. Hypertension 53:986–992. https://doi.org/10.1161/HYPERTENSIONAHA.109.131508

    Article  CAS  PubMed  Google Scholar 

  • Thijssen DH et al (2011) Assessment of flow-mediated dilation in humans: a methodological and physiological guideline. Am J Physiol Heart Circ Physiol 300:H2-12. https://doi.org/10.1152/ajpheart.00471.2010

    Article  CAS  PubMed  Google Scholar 

  • Thijssen DH et al (2019) Expert consensus and evidence-based recommendations for the assessment of flow-mediated dilation in humans. Eur Heart J 40:2534–2547

    Article  Google Scholar 

  • Tinken TM et al (2009) Impact of shear rate modulation on vascular function in humans. Hypertension 54:278–285. https://doi.org/10.1161/HYPERTENSIONAHA.109.134361

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Townsend N, Wilson L, Bhatnagar P, Wickramasinghe K, Rayner M (2016) Nichols M (2016) Cardiovascular disease in Europe: epidemiological update. Eur Heart J 37:3232–3245

    Article  Google Scholar 

  • van de Hoef TP, Meuwissen M, Escaned J, Davies JE, Siebes M, Spaan JA, Piek JJ (2013) Fractional flow reserve as a surrogate for inducible myocardial ischaemia. Nat Rev Cardiol 10:439–452. https://doi.org/10.1038/nrcardio.2013.86

    Article  PubMed  Google Scholar 

  • Van Nunen LX et al (2015) Fractional flow reserve versus angiography for guidance of PCI in patients with multivessel coronary artery disease (FAME): 5-year follow-up of a randomised controlled trial. Lancet 386:1853–1860. https://doi.org/10.1016/s0140-6736(15)00057-4

    Article  Google Scholar 

  • Widlansky ME, Gokce N, Keaney JF Jr, Vita JA (2003) The clinical implications of endothelial dysfunction. J Am Coll Cardiol 42:1149–1160

    Article  CAS  Google Scholar 

  • Woodman RJ et al (2001) Improved analysis of brachial artery ultrasound using a novel edge-detection software system. J Appl Physiol 1985 91:929–937

    CAS  PubMed  Google Scholar 

  • Wu SP, Ringgaard S, Oyre S, Hansen MS, Rasmus S, Pedersen EM (2004) Wall shear rates differ between the normal carotid, femoral, and brachial arteries: An in vivo MRI study. J Magn Reson Imaging 19:188–193. https://doi.org/10.1002/Jmri.10441

    Article  PubMed  Google Scholar 

  • Ziegler T, Bouzourene K, Harrison VJ, Brunner HR, Hayoz D (1998) Influence of oscillatory and unidirectional flow environments on the expression of endothelin and nitric oxide synthase in cultured endothelial cells. Arterioscler Thromb Vasc Biol 18:686–692

    Article  CAS  Google Scholar 

Download references

Funding

MB is financially supported by a grant from the Fonds de Recherche du Québec–Santé (FRQ-S) and the Cardiometabolic Healthy, Diabetes and Obesity Research Network (CMDO). DG is supported by a NHMRC Principal Research Fellowship (APP1080914).

Author information

Author notes

  1. Dick H. J. Thijssen and Daniel J. Green contributed equally as senior.

Authors and Affiliations

  1. Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, UK

    Ellen A. Dawson, Maxime Boidin, Ruth Thompson & Dick H. J. Thijssen

  2. Cardiovascular Prevention and Rehabilitation (EPIC) Center, Montreal Heart Institute, Montreal, Canada

    Maxime Boidin

  3. School of Kinesiology and Exercise Science, Faculty of Medicine, Université de Montréal, Montreal, Canada

    Maxime Boidin

  4. School of Sport, Exercise and Rehabilitations Sciences, University of Birmingham, Birmingham, UK

    Nigel T. Cable

  5. Department of Physiology, Research Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands

    Dick H. J. Thijssen

  6. School of Human Sciences (Exercise and Sport Science), The University of Western Australia, Perth, WA, Australia

    Daniel J. Green

Authors
  1. Ellen A. Dawson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maxime Boidin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ruth Thompson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nigel T. Cable
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dick H. J. Thijssen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Daniel J. Green
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors whose names appear on the submission: (1) made substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data; or the creation of new software used in the work; (2) drafted the work or revised it critically for important intellectual content; (3) approved the version to be published; and (4) agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Corresponding author

Correspondence to Ellen A. Dawson.

Ethics declarations

Conflict of interest

All authors declare no conflict of interests.

Additional information

Communicated by Narihiko Kondo.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dawson, E.A., Boidin, M., Thompson, R. et al. Impact of proximal and distal cuff inflation on brachial artery endothelial function in healthy individuals. Eur J Appl Physiol 121, 1135–1144 (2021). https://doi.org/10.1007/s00421-021-04605-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00421-021-04605-8

Keywords

Search

Navigation