Sympathetic activation markedly reduces endothelium-dependent, flow-mediated vasodilation

OBJECTIVES: We sought to evaluate whether increased sympathetic outflow may interfere with flow-mediated dilation (FMD). BACKGROUND: Endothelial function, assessed as FMD, is frequently used as an intermediate end point in intervention studies. Many disease states with increased sympathetic tone are also characterized by endothelial dysfunction. METHODS: Sixteen healthy volunteers underwent FMD studies with and without concomitant sympathetic stimulation. Intra-arterial nitroglycerin (NTG) infusion was used to assess endothelium-independent vasodilation. Pathophysiologically relevant sympathetic stimulation was achieved by baroreceptor unloading, using a lower body negative pressure box. In a subset of eight volunteers, this protocol was repeated during loco-regional alpha-adrenergic blockade by intra-arterial infusion of phentolamine (PE). Reactive hyperemic flow was assessed with strain-gauge phlethysmography. RESULTS: Overall, FMD responses (8.3 +/- 3.4%) were significantly attenuated by concomitant sympathetic stimulation (3.6 +/- 3.4%, p < 0.01). Loco-regional alpha-adrenergic blockade had no effect on baseline FMD responses (10.7 +/- 4.7%), whereas the attenuation by sympathetic stimulation was abolished completely during PE co-infusion (11.5 +/- 3.3%). During intra-arterial NTG infusions, arterial diameters relative to baseline were not significantly different between the four possible stages. CONCLUSIONS: Sympathetic stimulation, at a clinically relevant range, significantly impairs the FMD response by an alpha-adrenergic mechanism.