son. Effect of acute sympathetic nervous system activation on flowmediated dilation of brachial artery. Am J Physiol Heart Circ Physiol 290: H1446 -H1453, 2006. First published November 11, 2005 doi:10.1152/ajpheart.00771.2005.-We tested the hypothesis that flow-mediated dilation (FMD) of the brachial artery would be impaired by acute increases in sympathetic nervous system activity (SNA) in models where similar peak shear stress stimulus was achieved by varying the duration of forearm muscle ischemia. Eleven healthy young men were studied under four different conditions, each with its own control: lower body suction (LBS), cold pressor test (CPT), mental arithmetic task (MAT), and activation of muscle chemoreflex (MCR). The duration of ischemia before observation of FMD by ultrasound imaging was 5 min each for control, LBS, and CPT; 3 min for MAT; and 2-min for MCR. Peak shear rate was not different between control and any of the SNA conditions, although total shear in the first minute was reduced in MAT. MCR was the only condition in which brachial artery vasoconstriction was observed before forearm occlusion [4.38 (SD 0.53) vs. control 4.60 (SD 0.53) mm, P Ͻ 0.05]; however, diameter increased to the same absolute value as that of the control, so the percent FMD was greater for MCR . During SNA, the increase in plasma cortisol from baseline was significant only for MCR; the increase in plasma norepinephrine was significant for MCR, LBS, and CPT; and the increase in epinephrine was significant only for MCR. These results showed that the four models employed to achieve increases in SNA had different effects on baseline brachial artery diameter and that blunted FMD is not a general response to increased SNA. endothelium; shear stress; muscle chemoreflex; cold pressor test; mental stress FLOW-MEDIATED DILATION (FMD) is studied by high-resolution ultrasound imaging of the change in conduit artery vessel dimension in response to a sudden increase in blood flow after release of circulatory occlusion. When compared with that in healthy, young subjects, FMD is impaired in patients with coronary artery disease (27, 40), as well as essential (11, 28) and white-coat (13) hypertension. Reduced FMD reflects impaired endothelial function, which has been found to be an independent risk factor of coronary artery disease (6, 12). Some evidence suggests that FMD might also be impaired in apparently healthy subjects during an acute stress that elevates sympathetic nervous system activity (SNA) (18,24,35). However, these findings are not universal (17) and might depend on the nature of the stress and the experimental design. Lind et al. (24) concluded that acute increases in SNA with mental arithmetic and cold pressor tests impaired FMD when expressed relative to blood flow stimulus. Impaired FMD was also found during application of lower body suction (18), but a different study (17) of a mental arithmetic challenge reported enhanced FMD. Unfortunately, the magnitude of reactive hyperemia or shear stress was not measured in thi...