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

Abstract

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 α₁-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.

Keywords: blood flow regulation; vascular aging; vascular function.