Aging is characterized by increased sympatho-excitation, expressed through both the α-adrenergic and RAAS (renin–angiotensin–aldosterone) pathways. Although the independent contribution of these two pathways to elevated vasoconstriction with age may be substantial, significant cross-talk exists that could produce potentiating effects. To examine this interaction, 14 subjects (n=8 young, n=6 old) underwent brachial artery catheterization for administration of AngII (angiotensin II; 0.8–25.6 ng/dl per min), NE [noradrenaline (norepinephrine); 2.5–80 ng/dl per min] and AngII with concomitant α-adrenergic antagonism [PHEN (phentolamine); 10 μg/dl per min]. Ultrasound Doppler was utilized to determine blood flow, and therefore vasoconstriction, in both infused and contralateral (control) limbs. Arterial blood pressure was measured directly, and sympathetic nervous system activity was assessed via microneurography and plasma NE analysis. AngII sensitivity was significantly greater in the old, indicated by both greater maximal vasoconstriction (−59±4% in old against −48±3% in young) and a decreased EC50 (half-maximal effective concentration) (1.4±0.2 ng/dl per min in old against 2.6±0.7 μg/dl per min in young), whereas the maximal NE-mediated vasoconstriction was similar between these groups (−58±9% in old and −62±5% in young). AngII also increased venous NE in the old group, but was unchanged in the young group. In the presence of α-adrenergic blockade (PHEN), maximal AngII-mediated vasoconstriction in the old was restored to that of the young (−43±8% in old and −39±6% in young). These findings indicate that, with healthy aging, the increased AngII-mediated vasoconstriction may be attributed, in part, to potentiation of the α-adrenergic pathway, and suggest that cross-talk between the RAAS and adrenergic systems may be an important consideration in therapeutic strategies targeting these two pathways.
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November 27 2012
Angiotensin II potentiates α-adrenergic vasoconstriction in the elderly
Zachary Barrett-O’Keefe;
Zachary Barrett-O’Keefe
*Department of Exercise and Sport Science, University of Utah, Salt Lake City, UT 84148, U.S.A.
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Melissa A. H. Witman;
Melissa A. H. Witman
†Department of Internal Medicine, University of Utah, Salt Lake City, UT 84132, U.S.A.
‡Geriatric Research, Education, and Clinical Center, VAMC, Salt Lake City, UT 84148, U.S.A.
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John Mcdaniel;
John Mcdaniel
§Cleveland VA Medical Center, Cleveland, OH 44106, U.S.A.
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Anette S. Fjeldstad;
Anette S. Fjeldstad
∥Department of Neurology, University of Utah, Salt Lake City, UT 84132, U.S.A.
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Joel D. Trinity;
Joel D. Trinity
†Department of Internal Medicine, University of Utah, Salt Lake City, UT 84132, U.S.A.
‡Geriatric Research, Education, and Clinical Center, VAMC, Salt Lake City, UT 84148, U.S.A.
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Stephen J. Ives;
Stephen J. Ives
†Department of Internal Medicine, University of Utah, Salt Lake City, UT 84132, U.S.A.
‡Geriatric Research, Education, and Clinical Center, VAMC, Salt Lake City, UT 84148, U.S.A.
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Jamie D. Conklin;
Jamie D. Conklin
†Department of Internal Medicine, University of Utah, Salt Lake City, UT 84132, U.S.A.
‡Geriatric Research, Education, and Clinical Center, VAMC, Salt Lake City, UT 84148, U.S.A.
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Van Reese;
Van Reese
‡Geriatric Research, Education, and Clinical Center, VAMC, Salt Lake City, UT 84148, U.S.A.
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Sean Runnels;
Sean Runnels
¶Department of Anesthesiology, University of Utah, Salt Lake City, UT 84132, U.S.A.
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David E. Morgan;
David E. Morgan
¶Department of Anesthesiology, University of Utah, Salt Lake City, UT 84132, U.S.A.
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Mikael Sander;
Mikael Sander
**Department of Cardiology and Copenhagen Muscle Research Center, Copenhagen National Hospital, Copenhagen, Denmark
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Russell S. Richardson;
Russell S. Richardson
*Department of Exercise and Sport Science, University of Utah, Salt Lake City, UT 84148, U.S.A.
†Department of Internal Medicine, University of Utah, Salt Lake City, UT 84132, U.S.A.
‡Geriatric Research, Education, and Clinical Center, VAMC, Salt Lake City, UT 84148, U.S.A.
††University of Utah Center on Aging, Salt Lake City, UT 84132, U.S.A.
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D. Walter Wray
*Department of Exercise and Sport Science, University of Utah, Salt Lake City, UT 84148, U.S.A.
†Department of Internal Medicine, University of Utah, Salt Lake City, UT 84132, U.S.A.
‡Geriatric Research, Education, and Clinical Center, VAMC, Salt Lake City, UT 84148, U.S.A.
††University of Utah Center on Aging, Salt Lake City, UT 84132, U.S.A.
Correspondence: Dr D. Walter Wray (email [email protected]).
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Publisher: Portland Press Ltd
Received:
August 07 2012
Revision Received:
September 12 2012
Accepted:
September 18 2012
Accepted Manuscript online:
September 18 2012
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2013 Biochemical Society
2013
Clin Sci (Lond) (2013) 124 (6): 413–422.
Article history
Received:
August 07 2012
Revision Received:
September 12 2012
Accepted:
September 18 2012
Accepted Manuscript online:
September 18 2012
Citation
Zachary Barrett-O’Keefe, Melissa A. H. Witman, John Mcdaniel, Anette S. Fjeldstad, Joel D. Trinity, Stephen J. Ives, Jamie D. Conklin, Van Reese, Sean Runnels, David E. Morgan, Mikael Sander, Russell S. Richardson, D. Walter Wray; Angiotensin II potentiates α-adrenergic vasoconstriction in the elderly. Clin Sci (Lond) 1 March 2013; 124 (6): 413–422. doi: https://doi.org/10.1042/CS20120424
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