Characterizing the Stimulus-Response Relationship Between Endothelial Dependent Flow Mediated Dilation and Shear Stress

Abstract

The vascular endothelium is a single layer of cells that lines the interior surface of our blood vessels. The endothelium plays a key role in vasoprotection and vasoregulation and its proper function is therefore essential to the maintenance of vascular health. The endothelial cells respond to the frictional force (shear stress (SS)) that occurs with an increase in blood flow. As a response, vasoactive substances are released, causing the artery to dilate, this is termed flow-mediated dilation (FMD). Endothelial cell function can be assessed by measuring the vasodilatory response to an increase in SS. Currently however, our ability to interpret the results of FMD assessment in order to make accurate judgements regarding arterial health is hindered by an incomplete understanding of the “dose-response” relationship between SS and FMD. The dose-response relationship is characterized by 1) the SS stimulus required to elicit an FMD response (threshold), 2) the magnitude of dilation for a given increase in SS (the slope of the SS-FMD relationship), and 3) the point at which further increases in SS no longer elicit dilation (the ceiling). The primary purpose of the current study was to characterize the magnitude and day-to-day variability of the parameters described above. N=20 males (mean 22-years). Brachial artery diameter (BAD) and blood velocity (BV) were assessed with echo and Doppler ultrasound. SS was estimated as shear rate (SR=BV/BAD). Subjects performed 2 incremental handgrip exercise trials on two separate visits (V1 and V2). CV=co-efficient of variation. The SS-FMD relationship was characterized by a shallow slope followed by an inflection point (threshold (T1)) and a steeper slope (pre vs. post T1 slope p=0.002). There was no difference between V1 vs. V2 in the SR-FMD slope or threshold (p>0.05), but there was considerable within-subject variability in the SR-FMD parameters: pre-T1 slope CV = 47.0 ± 33.1%; post-T1 slope CV = 55.3 ± 40.7%; T1 CV = 25.6 ± 6.3%. In conclusion, %FMD did not plateau with increasing SR, therefore no ceiling was identified. The inflection in slope may indicate the involvement of different or additional vasodilator mechanisms post-threshold.