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This study investigated the impact of long-duration head-down bedrest (HDBR) on the central and peripheral components of the sympathetic baroreflex in males and females. Microneurography was used to measure integrated muscle sympathetic nerve activity (MSNA). Signal averaging was used to quantify sympathetic transduction of mean arterial pressure (MAP) and total peripheral resistance (TPR) in 13 males and 12 females before and after 60 days of −6° HDBR. Under baseline conditions, when analyses were stratified by biological sex, HDBR attenuated transduction of MSNA bursts to MAP responses in males (pre-HDBR: Δ1.4 ± 0.5 mmHg, post-HDBR: Δ1.0 ± 0.4 mmHg; η2 = 0.49, p = 0.005) but not females (p = 0.143). HDBR did not affect baseline integrated MSNA in males or females. Females performed lower body negative pressure (LBNP) at −20, −30, and −45 mmHg. HDBR reduced stroke volume (η2 = 0.89, p < 0.001) and increased TPR (η2 = 0.56, p < 0.001) across all levels of LBNP but did not affect MSNA burst frequency, burst amplitude, or baroreflex gain indices (all p ≥ 0.191). In females, HDBR augmented sympathetic transduction of TPR at −45 mmHg LBNP (pre-HDBR: Δ0.2 ± 0.2 mmHg/L/min, post-HDBR: Δ0.4 ± 0.4 mmHg/L/min; η2 = 0.25, p < 0.001). These data suggest that: (1) biological sex influences the impact of HDBR on baseline sympathetic transduction of blood pressure and (2) among females, vasoconstrictor responses to sympathetic bursts elicited by simulated orthostasis are augmented to compensate for reduced stroke volume after long-duration HDBR.

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