Pharmacological Modulation of Leg Shear Rate Profile in Young and Older Adults

Abstract

Aging alters the shear rate profile in the arm, characterized by increased oscillatory (bidirectional) shear, potentially from progressive increases in sympathetic nervous system activity. However, the extent to which the shear profile in the atheroprone vasculature of the leg is mediated by sympathetic overactivity via α-adrenergic receptor activation is unknown. We sought to determine how pharmacological modulation of α-adrenergic receptor activity alters shear in the femoral artery with aging. We hypothesized, within the leg, that increased α-adrenergic vasoconstriction would lead to a pro-atherosclerotic shear profile in young adults while α-adrenergic blockade would improve the shear rate profile in older adults, as previously reported in the arm. Resting femoral artery shear rate profiles were assessed in five young (4M/1F, 26±5 yr) and seven older (4M/3F, 65±7 yr) adults during saline (control), phentolamine (PHEN, nonselective α -adrenergic antagonist), and phenylephrine (PE, a selective α-adrenergic agonist) intra-arterial infusions using Doppler ultrasound. Under control conditions, there were no age-related differences in antegrade, retrograde, or total (antegrade + retrograde) shear rates. During PHEN infusion, antegrade shear increased in both young and older adults (Y: 597±214 v. 1011±313 s−1; O: 412±168 v. 648±334 s−1, p<0.05 for both), while retrograde (Y: 122±49 v. 62±21 s−1; O: 109±59 v. 54±43 s−1, p<0.05 for both), and oscillatory shear decreased (Y: 0.17±0.01 v. 0.06±0.01; O: 0.20±0.02 v. 0.09±0.02, p<0.05 for both) compared to control. Although the magnitude of change was similar between age groups, antegrade and total shear were greater in young following PHEN. Infusion of PE had no effect on antegrade (Y: p=0.16; Op=0.78,), retrograde (Y: p=0.83; O: p=0.17), and oscillatory shear (Y: p=0.25; O: p=0.09) but did cause an age-related separation in antegrade and total shear such that the young were greater following PE. Collectively, these preliminary data suggest withdrawal of α-adrenergic vasoconstriction with PHEN leads to a more favorable shear pattern (i.e., increased antegrade shear, and decreased retrograde and oscillatory) within the femoral artery, independent of age. Overall, these findings indicate that femoral shear rate may be influenced by the α-adrenergic system in a manner that is uniquely different from what has been previously reported in the arm. R01HL142603, I01CX001999, IK2RX001215. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.