Shear Stress Mediates Endothelial Adaptations to Exercise Training in Humans

Abstract

Abstract-Although episodic changes in shear stress have been proposed as the mechanism responsible for the effects of exercise training on the vasculature, this hypothesis has not been directly addressed in humans. We examined brachial artery flow-mediated dilation, an index of NO-mediated endothelial function, in healthy men in response to an acute bout of handgrip exercise and across an 8-week period of bilateral handgrip training. Shear stress responses were attenuated in one arm by cuff inflation to 60 mm Hg. Similar increases were observed in grip strength and forearm volume and girth in both limbs. Acute bouts of handgrip exercise increased shear rate (PϽ0.005) and flow-mediated dilation percentage (PϽ0.05) in the uncuffed limb, whereas no changes were evident in the cuffed arm. Handgrip training increased flow-mediated dilation percentage in the noncuffed limb at weeks 2, 4, and 6 (PϽ0.001), whereas no changes were observed in the cuffed arm. Brachial artery peak reactive hyperemia, an index of resistance artery remodeling, progressively increased with training in the noncuffed limb (PϽ0.001 and 0.004); no changes were evident in the cuffed arm. Neither acute nor chronic shear manipulation during exercise influenced endothelium-independent glyceryl trinitrate responses. These results demonstrate that exercise-induced changes in shear provide the principal physiological stimulus to adaptation in flow-mediated endothelial function and vascular remodeling in response to exercise training in healthy humans. (Hypertension. 2010;55:312-318.)

Time-course of vascular adaptations during 8 weeks of exercise training in subjects with type 2 diabetes and middle-aged controls

“…In keeping with previous studies in healthy young volunteers, exercise training lead to a rapid functional increase in both groups. Whilst continued exercise training has been associated with normalisation of endothelial function after 6-8 weeks in young healthy subjects (Tinken et al 2008;Tinken et al 2010;Birk et al 2012), we observed preservation of the increase in brachial artery endothelial function after 6-8 weeks in both groups in this study. This suggests the presence of a distinct time-course in vascular adaptations to exercise training in middle-aged type 2 diabetes patients and older subjects, compared with young healthy individuals.…”

“…cycling/running exercise) (Birk et al 2012;Tinken et al 2008) or small muscle group (i.e. handgrip exercise) (Tinken et al 2010) training in healthy young volunteers have consistently demonstrated that 2 weeks of exercise training is sufficient to significantly enhance vascular function. This initial rapid increase in vascular function is often normalised after 6-8 weeks of training.…”

Impact of 2‐Weeks Continuous Increase in Retrograde Shear Stress on Brachial Artery Vasomotor Function in Young and Older Men

“…Previous studies provide strong evidence that (repeated) elevations in antegrade or mean SR represent a potent hemodynamic stimulus that acutely and chronically alters vascular function and structure 1, 5, 6, 7, 8, 9, 10. As a logical follow‐up study from initial findings that acute elevation in retrograde shear induces impairment in endothelial function,2 this study aimed to assess the effect of chronic (ie, 2 weeks) manipulation of retrograde SR in humans in vivo.…”

“…Typically, shear stress follows a cyclic pattern, directed towards the periphery during systole (antegrade shear) and, under some circumstances, directed backwards to the heart during diastole (retrograde shear) 4. Elevations in antegrade shear stress are associated with potentially beneficial effects on the vessel wall 1, 5, 6, 7, 8, 9, 10. In contrast, elevation in retrograde shear stress may be potentially detrimental 2, 10, 11.…”

“…Several studies have explored the impact of repeated exposure to elevations in antegrade shear stress via training, heating, or in vitro manipulation of antegrade shear 7, 13, 14, 15, 16, 17. These studies consistently report a dose‐dependent increase in arterial caliber and improvement in endothelial function, possibly through upregulation of endothelial nitric oxide synthase 1, 18.…”