Prolonged Bed Rest Is a Water-Losing Phenotype Associated With Increased Blood Pressure

Objective: Tissue sodium accumulation is associated with hypertension and was recently linked to water homeostasis. Animal studies suggest that sodium accumulates in tissues during dehydration to prevent skin water losses by vasoconstriction, but at the expense of increased blood pressure. In collaboration with the European Space Agency, we tested the hypothesis that prolonged bed rest induces renal water loss through osmotic diuresis and subsequently increases blood pressure.Design and method: Twenty-four healthy male subjects underwent 60-day 6° head-down tilt bed rest with strictly controlled dietary intake. Eight were randomized to strict bed rest (control group) and 16 to a countermeasure protocol consisting of exercise and/or artificial gravity. Water, sodium and urea balance were assessed with daily 24-hour urine collections. We used thigh magnetic resonance imaging to quantify muscle mass loss. Blood pressure was measured using automated devices. Systemic vascular resistance index (SVRI) was assessed using Finapres®. We used linear mixed-effects models to compare data between groups and before-after bed rest. Results: Thigh fat-free muscle volume declined during bed rest in both groups, but more in controls (11±3% vs. 6±2%, p<0.001). Urine urea excretion increased in control subjects (7±7%, p=0.02), but not in the countermeasure group (2±7%, p=0.36; Fig A). In the control group fluid intake decreased (44±6 to 38±7 mL/kg/day, p=0.006; Fig B) while urinary output remained unchanged (28±6 vs. 27±6 mL/kg/day, p=0.82). Cumulative urinary sodium balance during 60-day bed rest was 1753 ± 331 mmol. During bed rest, blood pressure increased in control subjects but not in the countermeasure group (systolic 4.2%, 95% CI 1.8-6.7%, p=0.007; diastolic 6.1%, 95% CI 2.2-10.1%, p=0.004; Fig C). SVRI increased during early bed rest in controls (20±23% p=0.038; Fig D) and not in the countermeasure group (p=0.28). In controls, heart rate was 5±4% lower (p=0.013) during early bed rest and 7±7% (p=0.031) higher during late bed rest (Fig E). Conclusions: Prolonged bed rest is a water-losing phenotype, which increased blood pressure through an increase in vascular resistance. These responses were attenuated by countermeasures that preserved muscle mass and prevented osmotic diuresis.