title: Angiotensin II potentiates α-adrenergic vasoconstriction in the elderly.
abstract: 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.
authors.affiliation: Department of Exercise and Sport Science, University of Utah, Salt Lake City, UT 84148, USA.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Barrett-O'Keefe
authors.forename: Melissa A H
authors.initials: MA
authors.lastname: Witman
authors.forename: John
authors.initials: J
authors.lastname: McDaniel
authors.forename: Anette S
authors.initials: AS
authors.lastname: Fjeldstad
authors.forename: Joel D
authors.initials: JD
authors.lastname: Trinity
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Ives
authors.forename: Jamie D
authors.initials: JD
authors.lastname: Conklin
authors.forename: Van
authors.initials: V
authors.lastname: Reese
authors.forename: Sean
authors.initials: S
authors.lastname: Runnels
authors.forename: David E
authors.initials: DE
authors.lastname: Morgan
authors.forename: Mikael
authors.initials: M
authors.lastname: Sander
authors.forename: Russell S
authors.initials: RS
authors.lastname: Richardson
authors.forename: D Walter
authors.initials: DW
authors.lastname: Wray
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology; D000804:Angiotensin II / Q000494:pharmacology*; D004357:Drug Synergism; D006801:Humans; D009638:Norepinephrine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D012084:Renin-Angiotensin System / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D011942:Receptors, Adrenergic, alpha; D000804:Angiotensin II; D009638:Norepinephrine; D010646:Phentolamine