Pharmacological modulation of adrenergic tone alters the vasodilatory response to passive leg movement in young but not in old adults

• Published in: Journal of applied physiology (1985) Vol. 134; no. 5; pp. 1124 - 1134
• Main Authors: Fermoyle, Caitlin C, La Salle, D Taylor, Alpenglow, Jeremy K, Craig, Jesse C, Jarrett, Catherine L, Broxterman, Ryan M, McKenzie, Alec I, Morgan, David E, Birgenheier, Nathaniel M, Wray, D Walter, Richardson, Russell S, Trinity, Joel D
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01-05-2023
• Subjects: Adrenergic Agents - pharmacology; Aged; Blood flow; Blood pressure; Femoral artery; Hemodynamics; Humans; Leg; Leg - blood supply; Modulation; Movement - physiology; Phentolamine; Phenylephrine; Regional Blood Flow - physiology; Vasodilation; Vasodilation - physiology; blood flow regulation; vascular function; vascular aging
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.00682.2022

The age-related increase in α-adrenergic tone may contribute to decreased leg vascular conductance (LVC) both at rest and during exercise in the old. However, the effect on passive leg movement (PLM)-induced LVC, a measure of vascular function, which is markedly attenuated in this population, is unknown. Thus, in eight young (25 ± 5 yr) and seven old (65 ± 7 yr) subjects, this investigation examined the impact of systemic β-adrenergic blockade (propanalol, PROP) alone, and PROP combined with either α
-adrenergic stimulation (phenylephrine, PE) or α-adrenergic inhibition (phentolamine, PHEN), on PLM-induced vasodilation. LVC, calculated from femoral artery blood flow and pressure, was determined and PLM-induced Δ peak (LVC
) and total vasodilation (LVC
, area under curve) were documented. PROP decreased LVC
(PROP: 4.8 ± 1.8, Saline: 7.7 ± 2.7 mL·mmHg
,
< 0.001) and LVC
(PROP: 1.1 ± 0.7, Saline: 2.4 ± 1.6 mL·mmHg
,
= 0.002) in the young, but not in the old (LVC
,
= 0.931; LVC
,
= 0.999). PE reduced baseline LVC (PE: 1.6 ± 0.4, PROP: 2.3 ± 0.4 mL·min
·mmHg
,
< 0.01), LVC
(PE: 3.2 ± 1.3, PROP: 4.8 ± 1.8 mL·min
·mmHg
,
= 0.004), and LVC
(PE: 0.5 ± 0.4, PROP: 1.1 ± 0.7 mL·mmHg
,
= 0.011) in the young, but not in the old (baseline LVC,
= 0.199; LVC
,
= 0.904; LVC
,
= 0.823). PHEN increased LVC at rest and throughout PLM in both groups (drug effect:
< 0.05), however LVC
was only improved in the young (PHEN: 6.4 ± 3.1, PROP: 4.4 ± 1.5 mL·min
·mmHg
,
= 0.004), and not in the old (
= 0.904). Furthermore, the magnitude of α-adrenergic modulation (PHEN - PE) of LVC
was greater in the young compared with the old (Young: 3.35 ± 2.32, Old: 0.40 ± 1.59 mL·min
·mmHg
,
= 0.019). Therefore, elevated α-adrenergic tone does not appear to contribute to the attenuated vascular function with age identified by PLM.
Stimulation of α1-adrenergic receptors eliminated age-related differences in passive leg movement (PLM) by decreasing PLM-induced vasodilation in the young. Systemic β-blockade attenuated the central hemodynamic component of the PLM response in young individuals. Inhibition of α-adrenergic receptors did not improve the PLM response in older individuals, though withdrawal of α-adrenergic modulation augmented baseline and maximal vasodilation in both groups. Accordingly, α-adrenergic signaling plays a role in modulating the PLM vasodilatory response in young but not in old adults, and elevated α-adrenergic tone does not appear to contribute to the attenuated vascular function with age identified by PLM.