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2009; Kizhakekuttu et al. 2010). In the present study, we also demonstrated that during exercise these two methods of assessing diameters produced nearly identical results. Antegrade and retrograde blood velocities for each cardiac cycle were calculated as area above (antegrade) or below (retrograde) the curve, respectively, divided by the R�CR time interval. Thus, similar to mean velocity, the antegrade and retrograde values also reflect time-averaged blood velocities Selleckchem RO4929097 (Padilla et al. 2010, 2011b). Diameter and blood velocity measurements were used to calculate brachial artery blood flow and shear rate. Blood flow was calculated as Vm��(D2/4) �� 60, where Vm is time-average mean blood velocity (in centimetres per second), D is arterial diameter (in centimetres), and mean shear rate (per second) was defined as 4 XVmD?1 (Padilla et al. 2010, 2011b; Simmons et al. 2011). For calculations of antegrade and retrograde shear rate, antegrade and retrograde time-averaged blood velocities were used, respectively. Oscillatory shear index, an indicator of the magnitude of shear oscillation, was defined as follows: |retrograde shear|/(antegrade shear + |retrograde shear|) (Wu et al. 2004; Newcomer et al. 2008; Padilla et al. 2010, 2011b; Simmons et al. 2011). Note that the values for oscillatory shear range from 0 to 0.5, where a value of 0 corresponds to a unidirectional shear rate throughout the cardiac cycle and a value of 0.5 represents pure oscillation with a time-average shear equal to zero. Forearm vascular conductance (in millilitres per minute per millimetre of mercury) was calculated as the ratio of brachial artery blood flow to mean arterial pressure. check details A two-way (condition �� time) repeated-measures ANOVA was used to evaluate the time course of all variables of interest during cycling and forearm heating. When a significant interaction was found, simple main effects were evaluated. Significant simple main effects with more than one degree of freedom (i.e. time) were followed up with Dunnett's post hoc procedure to identify which time points deviated from baseline. All data are presented as means �� SEM. For all statistical tests, the �� level was set at INPP5D fourfold increase in forearm blood flow (P