Vascular ultrasound has been extensively applied in the clinical setting to noninvasively assess the endothelial function by means of the so-called brachial artery flow mediated dilation (FMD). Despite the usefulness in large-scale epidemiological studies, this approach has revealed some pitfalls for assessing vascular physiology and health in individual subjects. Mainly, a reliable FMD examination should be based on the simultaneous and reliable measurement of both the stimulus, i.e., the wall shear rate (WSR), and the response, i.e., the diameter change. However, multiple technical, practical, and methodological challenges must be faced to meet this goal. In this work, we present the technical developments needed to implement a system to enable the extensive and reliable clinical ultrasound FMD examination. It integrates both a hardware part, i.e., an upgraded version of the ultrasound advanced open platform (ULA-OP), and a software part, i.e., a signal processing and data analysis platform. The system was applied for a two-center pilot clinical study on 35 young and healthy volunteers. Therefore, we present here the results of a statistical analysis on magnitude, time-course, and kinetic parameters of WSR and diameter trends that allowed us to accurately explore the vasodilatory response to the dynamic WSR changes. Our observations demonstrate that a direct and accurate estimation of WSR stimulus by multigate spectral Doppler allows understanding brachial artery vasodilatory response to reactive hyperemia. Drawing inferences on WSR stimulus from the diameter response along with an inaccurate estimation of WSR may cause further uncertainties for the accurate interpretation of the FMD response.