Are observed sex differences in forearm exercise vasodilation mediated through differences in cytochrome P450 2C9 signaling?

Abstract

Previous research has identified that women have greater vasodilation during exercise at the same relative intensity when compared to men and these differences are not due to nitric oxide or cyclooxygenase mechanisms. Therefore, we tested the hypothesis that sex differences in exercising vasodilation were due to differences in cytochrome P450 2C9 signaling. Methods: 18 healthy young adults (11 females, F, 10 males, M, 22.0±3yrs, 23.9±4yrs, respectively) completed two 5 minute of bouts dynamic forearm exercise at 20% effort, supine with arms at heart level, separated by ≥ 72hrs. 120 min prior exercise participants ingested 150mg of fluconazole (FLZ) to inhibit cytochrome P450 2C9 or a placebo (microcrystalline cellulose, PLA) in randomized, single-blind, counter balanced fashion. All female participants were regularly menstruating and examined during days 1-5 of their cycle (early follicular phase). Forearm blood flow (FBF; Echo and Doppler ultrasound; ml/min), forearm lean mass (FLM; DXA, g), mean arterial pressure (MAP, finger photoplethysmography, mmHg) were measured to calculate relative forearm vascular conductance (rFVC) = FBF/100mmHg/100g FLM. Results: Expressed as mean ± SD. There were no differences or interaction observed in rFVC at rest (PLA, M: 3.5±2 vs F: 3.4±2, FLZ, M: 3.9±2 vs F:4.3±1, p=0.51, η2=0.02). Interestingly, while no significant interaction between sexes and treatments were found, a large effect size (η2) was observed (PLA, M: 23.9±10 vs F:26.2±7, FLZ, M:22.8±7 vs F:32.5±9, p=0.07, η2 =0.16). Expressing the data as the change in rFVC from rest to exercise yields the same interpretations. Conclusion: In contrast to our hypothesis, both sexes showed similar rFVC responses to dynamic forearm handgrip exercise with no effect of cytochrome P450 2C9 inhibition. However, the large observed effect size indicates this investigation is likely underpowered to observe an effect of sex and cytochrome P450 2C9 inhibition. Therefore, these data advocate for further data collection in this investigation and provide justification for additional research into mechanistic differences of skeletal muscle vascular control between men and women. This is the full abstract presented at the American Physiology Summit 2023 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.