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.
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.
Authors: Dick H J Thijssen; Mark A Black; Kyra E Pyke; Jaume Padilla; Greg Atkinson; Ryan A Harris; Beth Parker; Michael E Widlansky; Michael E Tschakovsky; Daniel J Green Journal: Am J Physiol Heart Circ Physiol Date: 2010-10-15 Impact factor: 4.733
Authors: Alfredo Gamboa; Luis E Okamoto; André Diedrich; Leena Choi; David Robertson; Ginnie Farley; Sachin Paranjape; Italo Biaggioni Journal: Am J Physiol Heart Circ Physiol Date: 2012-01-27 Impact factor: 4.733
Authors: Nia C S Lewis; Damian M Bailey; Gregory R Dumanoir; Laura Messinger; Samuel J E Lucas; James D Cotter; Joseph Donnelly; Jane McEneny; Ian S Young; Mike Stembridge; Keith R Burgess; Aparna S Basnet; Philip N Ainslie Journal: J Physiol Date: 2013-12-09 Impact factor: 5.182