title: Sympathetic activation markedly reduces endothelium-dependent, flow-mediated vasodilation.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Internal Medicine, Eemland Hospital, Amersfoort, The Netherlands.
authors.forename: Michel L
authors.initials: ML
authors.lastname: Hijmering
authors.forename: Erik S G
authors.initials: ES
authors.lastname: Stroes
authors.forename: Jobien
authors.initials: J
authors.lastname: Olijhoek
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Hutten
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Blankestijn
authors.forename: Ton J
authors.initials: TJ
authors.lastname: Rabelink
mesh_terms: D000328:Adult; D001161:Arteriosclerosis / Q000503:physiopathology*; D001794:Blood Pressure / Q000502:physiology; D001916:Brachial Artery / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D010812:Physical Stimulation; D011311:Pressoreceptors / Q000503:physiopathology; D012016:Reference Values; D012039:Regional Blood Flow / Q000502:physiology; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D014664:Vasodilation / Q000502:physiology*