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). In the +o( arm, SR was significantly greater than in the ~o( limb. Brachial artery diameter increased post- exercise in ~o( by 3% (50%HRmax; P>0.05 vs. baseline), 7% (70%HRmax; P<0.05) and 9% (85%HRmax; P<0.05). In the+?C arm, post-exercise brachial diameter increased at all exercise intensities (P<0.05) and was significantly greater (P<0.05) than in the ~?C limb at 50% (12%), 70%HRmax (14%) and 85%HRmax (15%). In conclusion, increases in shear rate during incremental lower limb exercise are associated with increases in brachial artery diameter. This response is exaggerated with larger SR induced by localised heating, indicating that leg exercise has systemic effects on arterial diameter and that SR is an important stimulus to vasodilation during exercise in humans. The second study examined brachial artery flow mediated dilation (FMD) (using high resolution echo-Doppler) pre, and post (0, 1, 2, 24hr) 3 bouts of acute 30 min exercise at different (50, 70 and 85% HRmaxl intensities. Shear rate area-under-the- curve (from cuff deflation to peak dilatation; SRAUcl was calculated as the eliciting stimulus for FMD. Both baseline diameter and SRAUC were elevated by exercise. With covariate-control of these variables, the change in brachial artery FMD was negligible after exercise (~5 minutes post exercise) at 50% HRmax (6.3?2.6 vs. 5.9?2.5%; 95%(1 for difference: -0.59 to 1.34%) whilst a larger changes in FMD were noted after the exercise bouts at 70% (6.1?1.8 vs. 4.7?1.9%; 95%(1 for difference: 0.08 to 2.58%) and at 85% HRmax (6.6?1.6 vs. 3.6?2.2%; 95%(1: 0.41 to 5.42%). A further 2-way ANOVA revealed there were no changes in FMD at any other time- point post exercise (1, 2, 24hrs) and FMD normalised by Ihr post. These data indicate, for the first time, a 'dose-response' relationship between exercise intensity and the reduction in FMD, even when exercise-mediated changes in shear and baseline diameter are accounted for. The purpose of Study 3 was to examine the contribution of shear stress to changes in vascular function in the non-exercising upper limbs in response to lower limb (systemic) cycling exercise training. Subjects participated in an 8-week cycle training study undertaken at 80% HRmax, with unilateral cuff inflation around the forearm during each exercise bout. FMD, partly NO-mediated endothelial function (i.e. ischaemic handgrip exercise (iEX)), and endothelium-independent dilation to a NO donor (i.e. glyceryl trinitrate (GTN)) were measured at 2, 4 and 8 weeks. Cycle training increased FMD in the non-cuffed limb at week 2 after which, responses returned towards baseline levels (5.8?4.1, 8.6?3.8, 7.4?3.5, 6.0?2.3 at 0, 2, 4 and 8 weeks, respectively; ANOVA: P=0.04). No changes in FMD were observed in the cuffed arm. In addition, no changes were evident in response to iEX or GTN in either the cuffed or non-cuffed arms (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, intervention-group), but remained near resting levels in the other 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), but not in the control group (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.
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