The effects of CYP450 inhibition on cerebrovascular control during rest and mild hypovolemia: An exploratory study in young, healthy adults.

Abstract

Cerebrovascular CYP450 is underexplored in humans. Twenty-three participants (12 females) completed familiarization and two experimental visits utilizing double-blind, randomized, crossover design. Participants ingested fluconazole (150 mg; FLZ, CYP450 inhibitor) or placebo (PLC, microcrystalline cellulose) followed by 120 min of supine rest. Five minutes of middle cerebral artery velocity (MCAv) and mean arterial pressure (MAP) were collected during rest (PLC/FLZBASE) and lower body negative pressure (LBNP; −20 mmHg; PLC/FLZLBNP). There was no interaction for MCAv, cerebrovascular conductance index (CVCi), resistance area product (RAP), critical closing pressure (CrCP), or transfer function variables. Bonferroni tests revealed only FLZ attenuated MCAv (FLZBASE 75.2 ± 11.3 cm•s−1 vs. FLZLBNP 70.6 ± 11.2 cm•s−1, p = 0.015, d = 0.713) and CVCi (FLZBASE 0.76 ± 0.12 cm•s−1•mmHg−1 vs. FLZLBNP 0.71 ± 0.11 cm•s−1•mmHg−1, p = 0.003, d = 0.865) during LBNP. LBNP lowered CrCP (PLCBASE 29.7 ± 9.3 mmHg vs. PLCLBNP 25.1 ± 11.3 mmHg, p = 0.002, d = 0.940) within PLC. RAP increased during LBNP (PLCBASE 0.96 ± 0.29 vs. PLCLBNP 1.08 ± 0.32, p = < 0.001, d = 1.28; FLZBASE 0.98 ± 0.24 vs. FLZLBNP 1.07 ± 0.23, p = < 0.001, d = 1.10). These data suggest a participatory, nonobligatory role of CYP450 in human cerebrovascular control.