Flow-Mediated Dilation Induced by a Sustained Shear Stress Stimulus: Repeatability and Impact of Endurance Exercise

Abstract

The endothelium is a single layer of cells that lines the inside of all arteries, the proper functioning of which is essential for vasoprotection and control of arterial dilation. Blood flow through an artery produces a frictional force on the endothelium called shear stress, which causes the artery to dilate. A larger magnitude of this ‘flow-mediated dilation’ (FMD) response indicates greater endothelial function. To date, FMD has primarily been experimentally assessed using a transient shear stress stimulus called reactive hyperemia (RH). There is a paucity of research available which assesses FMD using sustained increases in shear stress, which are more similar to the shear stress stimuli that an artery experiences in everyday life. Therefore, the objective of this dissertation was to further our understanding of the FMD response to sustained shear stress stimuli and how it is impacted acutely and chronically by endurance exercise. Methods: Repeated handgrip squeezing (HGEX) and calf plantar-flexion (LEX) were used create a sustained increase in shear stress, stimulating FMD in the brachial and superficial femoral arteries respectively. 1) HGEX-FMD was assessed before and after an acute bout of high-intensity exercise. The mechanisms of exercise’s effect on HGEX-FMD were interrogated via the consumption of the antioxidant vitamin C. 2) In the superficial femoral artery, the repeat-trial stability of LEX-FMD was compared to RH-FMD. 3) The EX-FMD and RH-FMD responses to 4 weeks of endurance exercise training were assessed in the brachial and superficial femoral arteries. Results: 1) Brachial artery HGEX-FMD was augmented by high intensity endurance exercise, and this effect was abolished by vitamin C consumption, suggesting a role of oxidative stress in this adaptation. 2) Superficial femoral artery LEX-FMD was shown to increase systematically upon repeated trials, but RH-FMD did not. 3) Training improved brachial artery RH-FMD, but not HGEX-FMD and not LEX- or RH-FMD in the superficial femoral artery. Conclusions: The FMD responses to sustained and transient shear stress stimuli are regionally different, functionally different, and differently effected by exercise-related interventions, supporting the idea that they measure different aspects of endothelial function.