Acute hyperoxia elicits decreases in muscle sympathetic nerve activity and action potential activation in a sex-dependent manner.

Acute hyperoxia (100 % oxygen) has been shown to reduce muscle sympathetic nerve activity (MSNA), suggesting that hyperoxia could be a potential strategy for lowering blood pressure. However, the efficacy of hyperoxia to reduce blood pressure (e.g., mean arterial pressure; MAP) remains unclear. Therefore, we compared MSNA and MAP responses to acute hyperoxia (1-min pokilocapnic + 3-min, PetO O + 300 Torr) between 18 females and 13 males. Baseline integrated total MSNA was not different between females and males (24 ± 7 vs 23 ± 8 bursts/min, respectively; P = 0.68) while MAP was lower in females than males (85 ± 7 vs 93 ± 7 mmHg; P < 0.01). Overall, hyperoxia evoked reductions in MSNA burst frequency (BF; P = 0.02) but not burst amplitude (BA; P = 0.82) or total MSNA (=BF ∗ BA; P = 0.26), To further probe these responses, 1-min nadir total MSNA response to hyperoxia were extracted within each participant. Total MSNA was reduced from baseline during nadir hyperoxia only in males (sex ∗ cond: P = 0.04). Females exhibited a bimodal distribution of sympatho-inhibitors (F) and non-inhibitors (F). F demonstrated limited reductions in BF (P = 0.11 vs inhibitors) coupled with increases in BA (P < 0.01 vs inhibitors), resulting in no net change in total MSNA (P < 0.01 vs inhibitors). Mechanistically, action potential (AP) detection analyses revealed that F increased AP firing during hyperoxia (baseline: 313 ± 172 vs hyperoxia: 404 ± 192 spikes/min; P = 0.02), whereas hyperoxia blunted AP firing in F (baseline: 387 ± 263 vs hyperoxia: 267 ± 199 spikes/min; P = 0.02). In sum, approximately 50 % of healthy females responded to acute hyperoxia with unexpected increases in AP firing. These data may suggest that benefit of hyperoxia as a sympatho-inhibitor may be limited in young and healthy females.