Key result
Normalized metaboreflex gain assessment abolishes sex differences in arterial pressure response.
Why the study?
The authors aimed to evaluate an innovative dose-response approach to assess metaboreflex with control of intramuscular metabolic perturbation and investigate potential sex differences.
Normalizing the metaboreflex response to the degree of intramuscular metabolic perturbation (metaboreflex gain) abolishes previously observed sex differences, highlighting the need to account for neuromuscular fatigue in such assessments.
Answers are grounded in this paper and cite their sources.
Normalizing metaboreflex to metabolic perturbation abolishes apparent sex differences; hypothesis-generating and should not yet change assessment practice.
Aim We aimed to evaluate an innovative dose–response approach to assess the metaboreflex with control of intramuscular metabolic perturbation (concept of metaboreflex gain). We also investigated potential sex differences in the metaboreflex using this new approach. Methods Thirty participants (15 females) completed one familiarization and two experimental visits to evaluate the method and assess its reproducibility. Each visit involved four consecutive bouts of sustained isometric knee extension at 20% of maximal voluntary force interspersed with 2 min of post‐exercise circulatory occlusion (PECO). Intramuscular metabolic perturbation was quantified indirectly via changes in quadriceps twitch force evoked by electrical stimulation of the femoral nerve (∆Q TW ). Metaboreflex gain was calculated as the ratio of ∆mean arterial pressure (∆MAP) during PECO to ∆Q TW . Results We found a gradual increase in ∆MAP ( p < 0.0001) that was linearly correlated with the gradual decrease in ∆Q TW ( p < 0.0001) during the exercise bouts ( r 2 = 0.93; p = 0.037). Bland–Altman analysis showed a mean bias of 0.3 ± 0.5 for metaboreflex gain. Males exhibited greater metaboreflex to PECO than females when assessed “classically” with no control of ∆Q TW (∆MAP; 49.1% ± 17.9% vs. 36.5% ± 8.7%; p = 0.020), whereas there was no sex difference when assessed using the metaboreflex gain (∆MAP/∆Q TW ; 1.3 ± 0.6 vs. 1.8 ± 1.3; p = 0.325). The metaboreflex gain was not consistent across exercise bouts, showing that contrasting conclusions might emerge between two single assessments performed at different levels of metaboreflex activation. Conclusion This study highlights the critical need for using a dose–response relationship while accounting for neuromuscular fatigue as a proxy for the metabolic stimulus when assessing the muscle metaboreflex in humans. Trial Registration Clinical trials registration number: NCT06775119
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Kouzkouz et al. (2026) studied Healthy (n=30). Post-exercise circulatory occlusion (PECO) with indirect control of intramuscular metabolic perturbation vs. Classical assessment without metabolic control was evaluated on Metaboreflex gain (∆MAP/∆QTW) comparing males and females (p=0.325). Assessing metaboreflex gain by normalizing the mean arterial pressure response to intramuscular metabolic perturbation abolished the apparent sex difference between males and females observed with classical assessment (1.3 vs 1.8, p=0.325).
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