Impact of inactivity and exercise on the vasculature in humans : the role of blood flow and shear stress on arterial adaptations in healthy males

Exercise training is known to increase endothelial function and provoke arterial remodelling both locally and systemically. This thesis was designed to further examine these relationships by investigating the acute response to different exercise intensities, with and without shear rate modification. Shear rate modification was also used to examine the impact of systemic exercise training on brachial haemodynamics. Finally, the effect of inactivity on vascular function and arterial remodelling were studied using novel models of inactivity. The aim of Study 1 was to examine the effect of shear stress on upper limb brachial artery dilation during acute cycle exercise of different intensities. The impact of three randomised bouts of 30 mins leg cycling (50, 70 and 85% HRmax) on brachial artery blood flow, shear rate (SR) and brachial diameter, was measured bilaterally and simultaneously. SR was further manipulated in one arm via forearm heating (40? 1? C) in a water bath (+0C) throughout the exercise bouts. Exercise induced stepwise increases in SR in the unheated arm (~0C) (P 0.05 vs. baseline), 7% (70%HRmax; P O.05) across the 8 week intervention period. These data suggest that lower limb cycle training induces a transient increase in upper limb vascular function in healthy young humans which is, at least partly, mediated via shear stress. Exercise training is associated with rapid changes in endothelial function, which occur within days of starting training. Whilst long-term physical inactivity has a strong effect on vascular structure, little is known about the immediate impact of inactivity on vascular function. Therefore, Study 4 measured changes in vascular function before, during (day 4) and after 8 days of unilateral forearm inactivity induced by wearing a sling on the non-dominant arm. Maximal handgrip strength of the inactive forearm decreased after 8 days, confirming physical deconditioning. There were no significant changes in brachial artery baseline diameter, FMD, iEX or GTN across the 8 days in either arm (P>0.05). A significant decrease in peak blood flow was found in the intervention arm (2-way interaction: P=0.03) that is suggestive of remodelling of forearm resistance vessels. However, measures of (largely and partly) NO-mediated endothelial conduit artery function were not altered across an 8 day period of inactivity. Whilst increases in mean arterial shear stress are known to induce improvements in arterial function and remodelling in humans, animal data have demonstrated that retrograde shear is associated with pro-atherogenic effects. However, relatively little is known regarding the effect of retrograde shear rate on vascular function in humans in vivo. In order to provoke retrograde shear, subjects wore a compression sleeve on one forearm for 8 clays. Measurements were taken before and during acute (lhr) exposure to a compression sleeve on baseline day O. Measurements were taken after 4 and 8 days exposure to the compression sleeve. There were no significant changes in mean or antegrade shear rate during exposure to the compression sleeve. However, the compression sleeve resulted in an immediate increase in retrograde shear rate in 6 subjects (P O.05, control-group)i.e. subjects in whom the compression sleeve did not increase retrograde shear were the control group. The intervention group demonstrated a significant decrease in FMD after 1 h compression sleeve (P O.05). After 8-days using the compression sleeve, no significant changes in FMD, iEX, or GTN-response in the intervention and control group (all P>O.05) were observed. In conclusion, short-term increases in retrograde shear rate decrease FMD, but not chronically. Data in this thesis provide evidence for the role of blood flow and shear stress, as a result of exercise and inactivity, and its immediate effects upon the vasculature.