Impact of Shear Rate Modulation on Vascular Function in Humans

Shear stress is an important stimulus to arterial adaptation in response to exercise and training in humans. We recently observed significant reverse arterial flow and shear during exercise and different antegrade/retrograde patterns of shear and flow in response to different types of exercise. The purpose of this study was to simultaneously examine flow-mediated dilation, a largely NO-mediated vasodilator response, in both brachial arteries of healthy young men before and after 30-minute interventions consisting of bilateral forearm heating, recumbent leg cycling, and bilateral handgrip exercise. During each intervention, a cuff inflated to 60 mm Hg was placed on 1 arm to unilaterally manipulate the shear rate stimulus. In the noncuffed arm, antegrade flow and shear increased similarly in response to each intervention (ANOVA; P<0.001, no interaction between interventions; P=0.71). Baseline flow-mediated dilation (4.6%, 6.9%, and 6.7%) increased similarly in response to heating, handgrip, and cycling (8.1%, 10.4%, and 8.9%, ANOVA; P<0.001, no interaction; P=0.89). In contrast, cuffed arm antegrade shear rate was lower than in the noncuffed arm for all of the conditions (P<0.05), and the increase in flow-mediated dilation was abolished in this arm (4.7%, 6.7%, and 6.1%; 2-way ANOVA: all conditions interacted P<0.05). These results suggest that differences in the magnitude of antegrade shear rate transduce differences in endothelial vasodilator function in humans, a finding that may have relevance for the impact of different exercise interventions on vascular adaptation in humans.

[1]  R S Paffenbarger,et al.  Physical Activity and Coronary Heart Disease in Men: The Harvard Alumni Health Study , 2000, Circulation.

[2]  G. Guyatt,et al.  Cardiac rehabilitation after myocardial infarction. Combined experience of randomized clinical trials. , 1988 .

[3]  J. Appl,et al.  Importance of hemodynamic forces as signals for exercise-induced changes in endothelial cell phenotype. , 2008, Journal of applied physiology.

[4]  C. Jones,et al.  Flow-mediated dilatation following wrist and upper arm occlusion in humans: the contribution of nitric oxide. , 2001, Clinical science.

[5]  W E Haefeli,et al.  Nitric oxide is responsible for flow-dependent dilatation of human peripheral conduit arteries in vivo. , 1995, Circulation.

[6]  Daniel Green,et al.  Assessment of brachial artery blood flow across the cardiac cycle: retrograde flows during cycle ergometry. , 2002, Journal of applied physiology.

[7]  P Vallance,et al.  Heterogenous Nature of Flow-Mediated Dilatation in Human Conduit Arteries In Vivo: Relevance to Endothelial Dysfunction in Hypercholesterolemia , 2001, Circulation research.

[8]  G. D. De Keulenaer,et al.  Tumour necrosis factor alpha activates a p22phox-based NADH oxidase in vascular smooth muscle. , 1998, The Biochemical journal.

[9]  Samia Mora,et al.  Physical Activity and Reduced Risk of Cardiovascular Events: Potential Mediating Mechanisms , 2007, Circulation.

[10]  S. Ebrahim,et al.  Exercise‐based Rehabilitation for Coronary Heart Disease , 2001, The Cochrane database of systematic reviews.

[11]  L. Naylor,et al.  Comparison of forearm blood flow responses to incremental handgrip and cycle ergometer exercise: relative contribution of nitric oxide , 2005, The Journal of physiology.

[12]  E. Benjamin,et al.  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. , 2002, Journal of the American College of Cardiology.

[13]  Don P Giddens,et al.  Role of xanthine oxidoreductase and NAD(P)H oxidase in endothelial superoxide production in response to oscillatory shear stress. , 2003, American journal of physiology. Heart and circulatory physiology.

[14]  K. Pyke,et al.  Peak vs. total reactive hyperemia: which determines the magnitude of flow-mediated dilation? , 2007, Journal of applied physiology.

[15]  David M. Herrington,et al.  Erratum: 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 (Journal of American College of Cardiology (2002) 39 (257-265)) , 2002 .

[16]  J P Cooke,et al.  Cardiovascular effects of exercise: role of endothelial shear stress. , 1996, Journal of the American College of Cardiology.

[17]  D. Thijssen,et al.  Does arterial shear explain the magnitude of flow-mediated dilation?: a comparison between young and older humans. , 2009, American journal of physiology. Heart and circulatory physiology.

[18]  D. Thijssen,et al.  Brachial artery blood flow responses to different modalities of lower limb exercise. , 2009, Medicine and science in sports and exercise.

[19]  H. Drexler,et al.  Physical training improves endothelial function in patients with chronic heart failure. , 1996, Circulation.

[20]  B. Parker,et al.  Pick your Poiseuille: normalizing the shear stimulus in studies of flow-mediated dilation. , 2009, Journal of applied physiology.

[21]  D. Hayoz,et al.  Influence of oscillatory and unidirectional flow environments on the expression of endothelin and nitric oxide synthase in cultured endothelial cells. , 1998, Arteriosclerosis, thrombosis, and vascular biology.

[22]  D. Green,et al.  Flow‐mediated dilatation in the superficial femoral artery is nitric oxide mediated in humans , 2008, The Journal of physiology.

[23]  M. Joyner,et al.  Exercise and cardiovascular risk reduction: time to update the rationale for exercise? , 2008, Journal of applied physiology.

[24]  Manish Prakash,et al.  Exercise capacity and mortality among men referred for exercise testing. , 2002, The New England journal of medicine.

[25]  D. Green,et al.  Effect of exercise training on endothelium‐derived nitric oxide function in humans , 2004, The Journal of physiology.

[26]  R Busse,et al.  Crucial role of endothelium in the vasodilator response to increased flow in vivo. , 1986, Hypertension.

[27]  D. Thijssen,et al.  Importance of Measuring the Time Course of Flow-Mediated Dilatation in Humans , 2008, Hypertension.

[28]  D. Playford,et al.  Improved analysis of brachial artery ultrasound using a novel edge-detection software system. , 2001, Journal of applied physiology.

[29]  R. Paffenbarger,et al.  Physical activity, all-cause mortality, and longevity of college alumni. , 1986, The New England journal of medicine.

[30]  D. Thijssen,et al.  Impact of Shear Rate Modulation on Vascular Function in Humans , 2009, Hypertension.

[31]  D. Green,et al.  The effect of combined aerobic and resistance exercise training on vascular function in type 2 diabetes. , 2001, Journal of the American College of Cardiology.

[32]  S. Dowd,et al.  The Frequency Dependent Response of the Vascular Endothelium to Pulsatile Shear Stress , 2006, American journal of physiology. Heart and circulatory physiology.

[33]  R M Nerem,et al.  Oscillatory shear stress stimulates adhesion molecule expression in cultured human endothelium. , 1998, Circulation research.

[34]  D. Thijssen,et al.  Retrograde Flow and Shear Rate Acutely Impair Endothelial Function in Humans , 2009, Hypertension.

[35]  Tzung K Hsiai,et al.  Pulsatile Versus Oscillatory Shear Stress Regulates NADPH Oxidase Subunit Expression: Implication for Native LDL Oxidation , 2003, Circulation research.

[36]  M. Hopman,et al.  Leg intravenous pressure during head-up tilt. , 2008, Journal of applied physiology.

[37]  D. Green,et al.  Effect of lower limb exercise on forearm vascular function: contribution of nitric oxide. , 2002, American journal of physiology. Heart and circulatory physiology.