Fluid-regulating hormones and plasma volume during 60 days of head-down bed rest with exercise during artificial gravity (BRACE)

Reductions in plasma volume (PV), a hallmark of spaceflight and its analog head-down-bed rest (HDBR), trigger compensatory release of renin and aldosterone to promote fluid retention. Artificial gravity (AG) and exercise have been proposed to counteract PV reductions during HDBR, but optimal protocols remain undefined. We investigated how simultaneous exercise and AG affects fluid-regulating hormones and PV during HDBR compared with exercise or sedentary control groups. We hypothesized that exercise + AG would protect PV and maintain fluid-regulating hormones at pre-HDBR levels, outperforming exercise and sedentary control groups. Twenty-four healthy males (29 ± 6 yr) underwent 60 days of 6° HDBR and were assigned to sedentary control (<i>n</i> = 8), exercise (<i>n</i> = 8), or exercise + AG (<i>n</i> = 8) groups. Exercise group participants performed near daily 30 min supine moderate-to-high-intensity interval cycling throughout HDBR, whereas exercise + AG participants performed the same exercise during 30 min of short-arm centrifugation with head-to-foot gravitational profiles based on resting G tolerance tests. Changes in PV, fluid-regulating hormones, and erythropoietin were assessed using carbon monoxide rebreathing and biochemical assays. HDBR reduced PV (<i>P</i> < 0.001), blood volume (<i>P</i> < 0.001), and hemoglobin mass (<i>P</i> < 0.001) in all groups, and reductions were inversely correlated with an increase in active renin (all <i>P</i> < 0.05; <i>r_rm</i> = -0.615, <i>r_rm</i> = -0.553, and <i>r_rm</i> = -0.426, respectively). Erythropoietin was reduced at HDBR day 3 (<i>P</i> < 0.001) irrespective of group. Exercise + AG responses did not differ from the exercise or control groups, with countermeasures failing to maintain PV or blunt fluid-regulating hormone release. These results contrast work showing benefit of gravity-like exposure after exercise on PV and suggests that AG should not be applied exclusively during exercise.<b>NEW & NOTEWORTHY</b> Artificial gravity (AG) combined with exercise was proposed to protect plasma volume during head-down bed rest (HDBR). Our results suggest that by performing exercise with simultaneous AG, the previously identified beneficial effect of gravity-like exposure after exercise during prolonged HDBR is lost. The lack of benefit of simultaneous exercise and AG on plasma volume and fluid-regulating hormones is likely attributable to activation of the muscle pump, attenuating fluid shifts during AG countermeasure sessions.