Abstract 10269: Angiotensin II Potentiates α-Adrenergic Vasoconstriction in the Elderly
Introduction: Aging is associated with increased activity of both the adrenergic and renin-angiotensin-aldosterone systems (RAAS), which may contribute to the well-known elevation in peripheral vasoconstriction with age, as well as the sequelae of geriatric hypertension. The individual contribution of each pathway may be exacerbated by the potentiating effects of ANG-II on alpha-adrenergic vasoconstriction, though this interaction has not been studied in healthy aging.
Hypothesis: We hypothesized that: (1) Alpha-adrenergic vasoconstriction would be similar between young and older, and (2) ANG-II-mediated vasoconstriction would be greater in the elderly than in young, but this age effect would be ablated in the presence of alpha-adrenergic antagonism.
Methods: Eleven subjects (n=6 young, 25±1 yrs; n=5 older, 65±1 yrs) underwent brachial artery catheterization for local administration of ANG-II (0.8–25 ng/dl/min), NE (2.5–80 ng/dl/min) and ANG-II with concomitant alpha adrenergic antagonism (phentolamine, 10 mcg/dl/min). Drug administration was balanced, with >30 min between drugs. Ultrasound Doppler was utilized to determine blood flow in infused and contralateral (control) arms, and vasoconstriction was quantified as % change in limb blood flow. Arterial blood pressure was measured directly, and heart rate was determined via 3-lead ECG.
Results: At maximal doses, ANG-II-mediated vasoconstriction was greater in old (−61±6%) compared to young (−48±4%, P = 0.01), while NE-induced vasoconstriction was similar (−58±9 older, −65±7 young, P>0.05). During phentolamine, ANG-II-mediated vasoconstriction was reduced in the elderly to that of the young (−43±8% older, −39±6% young, P>0.05). Arterial blood pressure, heart rate, and control arm blood flow remained unchanged throughout all infusions (P>0.05).
Conclusions: With healthy aging, alpha-adrenergic vasoconstriction is preserved while ANG-II vasoconstriction is elevated. This enhanced ANG-II receptor sensitivity may be attributed in part to potentiation of NE release, implicating “cross-talk” between the RAAS and alpha adrenergic systems as an important consideration when evaluating anti-hypertensive therapeutic strategies in the elderly.
- © 2010 by American Heart Association, Inc.