Lipid Infusion Enhances Sympathetic Transduction via Redox-Sensitive Pathways.

BACKGROUND: Elevated circulating lipids increase oxidative stress and impair vascular function, but their effects on sympathetic-vascular control in humans are not well understood. We tested the hypothesis that intravenous lipid infusion enhances sympathetic-vascular transduction and beat-to-beat arterial pressure variability in humans, and that these effects are mediated, in part, by oxidative stress. METHODS: In a randomized, double-blind, placebo-controlled crossover study, healthy adults underwent 2 hours of intravenous lipid infusion (20% Intralipid) with coinfusion of ascorbic acid or saline control. Endothelial function was assessed by brachial artery flow-mediated dilation, and muscle sympathetic nerve activity (MSNA) was recorded using microneurography. Sympathetic-vascular transduction was quantified by signal-averaging beat-to-beat mean arterial pressure (MAP) and brachial vascular conductance responses after spontaneous MSNA bursts. RESULTS: Plasma malondialdehyde increased during lipid+saline (peak: 48±12 versus BL: 42±11 ng/mL; P<0.01) and decreased with lipid+ascorbic acid (nadir: 34±12 versus baseline: 45±14 ng/mL; P<0.01). Lipid+saline reduced flow-mediated dilation (4.1±2.7 versus baseline: 6.8±3.2%; P<0.01), increased beat-to-beat MAP variability (1.7±0.5 versus baseline: 1.5±0.4 mm Hg; P=0.01), and augmented responses to large MSNA bursts for MAP (4.7±2.0 versus baseline: 3.4±1.4%; P=0.03) and vascular conductance (-9.3±3.4 versus BL: -6.7±3.7%; P=0.01). Despite lipid-mediated increases in MSNA burst amplitude, coinfusion of ascorbic acid was not associated with an increase in beat-to-beat MAP variability (1.6±0.4 versus baseline: 1.5±0.4 mm Hg; P=0.23) and MAP (4.4±0.9 versus baseline: 4.1±0.8%; P=0.37) and vascular conductance (-6.8±4.6 versus baseline: -9.4±5.5%; P<0.01) responses to large MSNA bursts, although reductions in flow-mediated dilation were observed (5.0±3.0 versus baseline: 8.1±3.8%; P<0.01). CONCLUSIONS: Lipid infusion enhances sympathetic-vascular transduction and arterial pressure variability, consistent with a redox-sensitive mechanism, while impairing endothelial function via pathways that ascorbic acid does not fully reverse. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04832009.