Amir Akbari Fakhrabadi1, Alexander A. Buelow1, Jacob E. Matney1, Sarah Skillett1, Chris Mixon1, Jiwon Song1, & J. Mikhail Kellawan1

1The University of Oklahoma, Norman, Oklahoma

PURPOSE: To investigate whether cytochrome P450 2C9 pathways contribute to brachial artery diameter (BAD) flow-mediated dilation (FMD) within and between sexes. METHODS: 20 healthy young adults (10 males 21±2 yr, 10 females 23±3 yr, regular menstruation cycle, examined during days 1-5 of their cycle) completed two randomized, single-blinded, counterbalanced experimental visits separated by ≥72hrs. Prior to laboratory arrival, all participants refrained from caffeine ≥12hrs, and vigorous exercise, alcohol, and NSAIDs ≥24 hrs. 2hrs before experiments, participants ingested 150 mg of fluconazole (cytochrome P450 2C9 inhibitor, FLZ) or placebo (250 mg microcrystalline cellulose, PLA). All study visits were completed in a quiet, temperature-controlled (20-22C), and dark environment with the participant in a supine position and arms at heart level. FMD was induced via upper arm BA occlusion for 5 min and pneumatic rapid cuff release. BAD and velocity recorded by duplex ultrasound for offline analysis using automated edge-detection and wall-tracking software. FMD responses were reported as maximal absolute (FMD-∆mm) and percent changes (FMD-∆%) in post-occlusion BAD (Peak-D) relative to pre-occlusion baseline BAD (BL-D). Cumulative shear rate calculated (SR-AUC, s-1) until Peak-D. RESULTS: Expressed as means ±SD. Our results confirmed that there were significant differences between sexes in BL-D (mm, PLA, M: 4.2±0.4 vs F: 3.2±0.2, FLZ, M: 4.1±0.5 vs F: 3.1±0.3, p<0.001, η2=0.72) and Peak-D (mm, PLA, M: 4.5±0.3 vs F: 3.5±0.3, FLZ, M: 4.5±0.4 vs F: 3.5±0.2, p<0.001, η2=0.721). However, there was no effect or interaction observed for FMD-∆mm (PLA, M: 0.36±0.11 vs F: 0.33±0.12, FLZ, M: 0.32±0.09 vs F: 0.36±0.09, p=0.3, η2=0.06) or FMD-∆% (PLA, M: 8.9±2.8 vs F: 10.2±3.4, FLZ, M: 8±2.7 vs F: 11.8±3.4, p=0.2, η2=0.08) despite the moderate effect sizes. No differences found for SR-AUC (PLA, M: 53429±36605 vs F: 53640±30485, FLZ, M: 55354±38671 vs F: 58739±24243, p=0.74, η2=0.006). CONCLUSION: Our findings indicate, while there are significant differences between sexes for BAD Peak-D and BL-D, CYP450 inhibition does not alter FMD and SR-AUC in both sexes. However, considering a moderate effect size observed in FMD, further data collection is warranted to investigate sex differences in vascular responses.

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