Inhibition of CYP450 pathways reduces functional sympatholysis in healthy young adults

• DOI: 10.1152/ajpregu.00173.2024
• Publication Date: 2025-04-21T11:20:13Z
• Authors: Alexander A. Buelow; Jacob E. Matney; Sarah M. Skillett; John D. Ashley; Jiwon Song; Chris Mixon; Amir Akbari Fakhr...; Matthew Stanford; Debra A. Bemben; Daniel J. Larson; J. Mikhail Kellawan
• Keywords: Crossover study

Functional sympatholysis, the blunting of sympathetic vasoconstriction during exercise, is critical for regulating exercise hyperemia. The role cytochrome P450-2C9 (CYP450) pathways in functional sympatholysis remain unclear. 21 participants (11 females) completed three study visits (2 experimental). Participants ingested a placebo (PLA) or CYP450 inhibitor fluconazole (FLZ) 120 minutes before testing double-blind, randomized, crossover design. Forearm blood flow (FBF) and mean arterial pressure (MAP) were continuously measured to calculate forearm vascular conductance (FVC) baseline, -20 mmHg lower body negative (LBNPrest), rhythmic handgrip (Ex) at 20% maximum voluntary contraction, with LBNP (LBNPex). FLZ did not change FVC baseline Ex (p>0.05). However, adding LBNPex reduced condition compared PLA (PLA: 2 ± 12 Δ% vs. FLZ: -12 13 Δ%, p<0.001, d: 0.9). A significant across time (Baseline + LBNPrest LBNPex) was observed (p<0.001, ηp² = 0.8), along effects (PLA FLZ) (p: 0.003, ηp²: 0.4) their interaction 0.05, 0.2). magnitude differed between conditions 107 41% 67 50%, p: 0.001, r: 0.7). Therefore, are mechanistically involved sympatholysis. inhibition does augment resting exercising responses without constrictor stimuli.