Hypoxic Sympatholysis: The Role of β-Adrenergic Receptors and Sex in Young Adults

Introduction: Sympathetic-mediated vasoconstriction is attenuated during physiological stress such as exercise, a phenomenon termed functional sympatholysis. Prior work suggests sympatholysis may not occur during hypoxia, but evidence is limited by β-adrenergic receptor (β-AR) blockade and mixed sex cohorts. Further, β-AR sensitivity may be greater in young females than males and may contribute to sympathetic-mediated vasoconstriction during hypoxia. The purpose of this study was to determine the roles of β-AR and sex on sympathetic-mediated vasoconstriction during hypoxia. We hypothesized that 1) hypoxia would attenuate norepinephrine (NE)-mediated vasoconstriction (i.e., hypoxic sympatholysis), 2) β-AR blockade would attenuate hypoxic sympatholysis, and 3) the effect of β-AR blockade on hypoxic sympatholysis would be greater in females than males. Methods: Eleven females (23±2 yrs; tested during early follicular phase) and 13 males (26±5 yrs) underwent brachial artery catheterization for local infusion of NE and propranolol (β-AR blockade). Participants completed 4 trials: 1) normoxia NE, 2) hypoxia NE, 3) normoxia NE+β-AR blockade, and 4) hypoxia NE+β-AR blockade. Normoxia was achieved by breathing room air (21% oxygen) whereas hypoxia was achieved by breathing ~10% oxygen air (arterial oxygen saturation 81±2 %). Forearm blood flow (FBF, venous occlusion plethysmography) and blood pressure (BP, brachial artery catheter) were continuously measured. Forearm vascular conductance (FVC) was calculated (FBF/mean BP) and reported as a relative change from baseline (%ΔFVC). Analyses included ANOVA (sex x β-AR blockade x hypoxia; Bonferroni post hoc) and unpaired t -tests. Results: A main effect of sex ( p = 0.040) demonstrated greater NE-mediated vasoconstriction in males than females. NE-mediated vasoconstriction was attenuated under hypoxia vs. normoxia in males (-48±8 vs. -61±13 %ΔFVC, p = 0.008) and females (-36±20 vs. -51±8 %ΔFVC, p = 0.046), demonstrating hypoxic sympatholysis which did not differ by sex (males 13±14 vs. females 15±15 %ΔFVC, p = 0.689). There was a significant β-blockade x hypoxia interaction ( p = 0.008) but no sex x β-blockade x hypoxia interaction ( p = 0.542). Consistent with this, β-blockade attenuated hypoxic sympatholysis vs. control in both males (-1±3 vs. 13±14 %ΔFVC) and females (6±14 vs. 15±15 %ΔFVC; main effect of β-AR blockade p = 0.005). Conclusions: Using gold-standard pharmacological interventions, we report attenuated NE-mediated vasoconstriction under hypoxia (demonstrating hypoxic sympatholysis), that did not differ by sex. β-AR blockade attenuated hypoxic sympatholysis, supporting a portion of hypoxic sympatholysis is β-AR-mediated in young adults. These data highlight an important role for β-AR in buffering sympathetic-mediated vasoconstriction during hypoxia, which may be critical for conditions where β-AR is impaired ( e.g., aging) and in situations of low oxygen ( e.g., high altitude, sleep apnea). National Institutes of Health (1R01HL153523). This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.