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; 1522-1601
• DOI: 10.1152/japplphysiol.00682.2022

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. 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 1 -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 Δpeak ) and total vasodilation (LVC AUC , area under curve) were documented. PROP decreased LVC Δpeak (PROP: 4.8 ± 1.8, Saline: 7.7 ± 2.7 mL·mmHg −1 , P < 0.001) and LVC AUC (PROP: 1.1 ± 0.7, Saline: 2.4 ± 1.6 mL·mmHg −1 , P = 0.002) in the young, but not in the old (LVC Δpeak , P = 0.931; LVC AUC , P = 0.999). PE reduced baseline LVC (PE: 1.6 ± 0.4, PROP: 2.3 ± 0.4 mL·min −1 ·mmHg −1 , P < 0.01), LVC Δpeak (PE: 3.2 ± 1.3, PROP: 4.8 ± 1.8 mL·min −1 ·mmHg −1 , P = 0.004), and LVC AUC (PE: 0.5 ± 0.4, PROP: 1.1 ± 0.7 mL·mmHg −1 , P = 0.011) in the young, but not in the old (baseline LVC, P = 0.199; LVC Δpeak , P = 0.904; LVC AUC , P = 0.823). PHEN increased LVC at rest and throughout PLM in both groups (drug effect: P < 0.05), however LVC Δpeak was only improved in the young (PHEN: 6.4 ± 3.1, PROP: 4.4 ± 1.5 mL·min −1 ·mmHg −1 , P = 0.004), and not in the old ( P = 0.904). Furthermore, the magnitude of α-adrenergic modulation (PHEN – PE) of LVC Δpeak was greater in the young compared with the old (Young: 3.35 ± 2.32, Old: 0.40 ± 1.59 mL·min −1 ·mmHg −1 , P = 0.019). Therefore, elevated α-adrenergic tone does not appear to contribute to the attenuated vascular function with age identified by PLM. NEW & NOTEWORTHY 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.