Regional heterogeneity in wall architecture and thickness may be present between conduit arteries in the upper and lower limbs in humans. These differences in wall architecture may, in turn, influence vascular responsiveness. Folkow proposed in the 1950s that heterogeneity in wall-to-lumen ratio (W:L) could contribute to differences in vascular responsiveness, but this hypothesis has never been directly confirmed in vivo. Our first aim was to examine wall thickness and W:L across arteries in the lower (common and superficial femoral) and upper limbs (brachial and radial) of healthy men (n=35) using high resolution ultrasound. In a subgroup (n=20) we examined the relationship between W:L of these arteries, physiological (flow-mediated dilation, FMD) and pharmacological vasodilation (glyceryl trinitrate, GTN). Diameter and wall thickness differed significantly across all arteries (ANOVA P<0.001), with smaller arteries having a relatively larger wall thickness. Moreover, we found a significant correlation between W:L and the FMD-response (r=0.55, P<0.001), which remained significant after correcting for the eliciting shear stress (r=0.47, P<0.001), indicating that W:L/FMD relationship was not primarily related to the impact of diameter on the shear rate stimulus to FMD. W:L also correlated strongly with the GTN-response (r=0.56, P<0.001) across all arteries studied. These results indicate that regional heterogeneity exists in W:L within, but also between, limbs. More importantly, differences in W:L contribute to differences in vascular functional responses, reinforcing the conceptual proposal of Folkow, who suggested that arteries with larger W:L exhibit exaggerated responses to vasoactive stimuli.
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