CLINICAL STUDY: ENDOTHELIAL FUNCTION
Sympathetic activation markedly reduces endothelium-dependent, flow-mediated vasodilation
Michel L. Hijmering, MD*,
Erik S. G. Stroes, MD, PhD ,*,
Jobien Olijhoek, MD ,
Barbara A. Hutten, MSc, PhD ,
Peter J. Blankestijn, MD, PhD|| and
Ton J. Rabelink, MD, PhD
* Department of Internal Medicine, Eemland Hospital, Amersfoort, The Netherlands
Vascular Medicine, Eemland Hospital, Amersfoort, The Netherlands
Clinical Epidemiology and Biostatistics, Academic Medical Centre, Amsterdam, The Netherlands
Internal Medicine, University Medical Center, Utrecht, The Netherlands
|| Department of Nephrology, University Medical Center, Utrecht, The Netherlands
Manuscript received January 5, 2001;
revised manuscript received October 31, 2001,
accepted November 13, 2001.
* Reprint requests and correspondence: Dr. Erik S. G. Stroes, F 4-250, Department of Vascular Medicine, Academic Medical Centre, Meibergdreef 9, P. O. Box 22660, 1100 DD, Amsterdam, The Netherlands.
e.s.stroes{at}amc.uva.nl
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.
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Abbreviations and Acronyms
| | ANOVA | | ANOVA | | analysis of variance | | FBF | | forearm blood flow | | FMD | | flow-mediated dilation | | LBNP | | lower body negative pressure | | MSNA | | muscle sympathetic nerve activity | | NO | | nitric oxide | | NTG | | nitroglycerin | | PE | | phentolamine |
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