Natriuretic Peptide Resetting in Astronauts.

When astronauts enter weightlessness, cephalad fluid shifts increase left ventricular dimensions, whereas central venous pressure is surprisingly reduced. More chronically, counterregulatory adjustments attenuate total blood volume; however, the internal jugular vein remains grossly dilated.1 This finding would raise suspicion for central volume overload in terrestrial medicine. Moreover, a single astronaut retained substantial amounts of sodium in space without body mass gain. It is possible that weightlessness alters osmotically inactive sodium storage, a recently recognized mechanism for human volume regulation.2,3 Prolonged −6° head-down bed rest, which produces cephalad volume shifts similar to those in weightlessness, elicited sustained increases in circulating atrial natriuretic peptide concentrations.4 Conversely, individual astronauts have shown reduced natriuretic peptide signalling in space.5 Cardiac natriuretic peptide deficiency could exacerbate central hypervolemia. We assessed natriuretic peptides in astronauts in the first study comparing lower-sodium and higher-sodium diets in space and on Earth. The SOLO study (Sodium Load in Microgravity) was approved by the Johnson Space Center institutional review board and the European Space Agency medical board. After giving informed consent, we tested 8 male astronauts (50±2.8 years old; weight, 85.61±8.89 kg) on both lower-sodium (2 g/d) and higher-sodium (5.5 g/d) diets for 5 consecutive days in space and 6 to 12 months after landing on Earth. In space, diets were applied in random order no earlier than 4 weeks into the mission. Dietary nutrient and water intakes were kept constant. Blood samples were obtained on day 5 of each intervention and analyzed for sodium, creatinine, midregional proatrial natriuretic peptide (MRproANP), NT-proBNP (N-terminal pro-B-type natriuretic peptide), and aldosterone. On Earth, samples were obtained while subjects were seated in the morning after they had traveled from the hotel to the study center. The same day, urinary sodium, creatinine, and body mass were measured. Body mass on the International Space Station was measured with the National Aeronautics and Space Administration’s Space Linear Acceleration Mass Measurement Device; on Earth, we used a standard scale. To gauge changes in central blood volume, we assessed thoracic bioimpedance in 16 cosmonauts (45.56±5.59 years old; weight, 79.88±6.94 kg) before launch, monthly onboard the International Space Station, and after return to Earth. The study in cosmonauts was approved by the Biomedicine Ethics Committee of the State Research Center of the Russian Federation, the Institute of Biomedical Problems, the Russian Academy of Science, and the subjects gave informed consent. On the lower-sodium diet, astronauts excreted 74.3±7.0 mmol of sodium per day (mean+SEM) in space and 82.6±10.3 mmol/d on Earth (P=0.172). On the higher-sodium diet, astronauts excreted 175±12 mmol/d in space and 196±13 mmol/d on Earth (P=0.249). Glomerular filtration rate was unchanged, whereas fractional sodium excretion increased similarly on the higher-sodium diet (P<0.001) in space and on Earth. Body mass was 83.7±3.1 kg on the lower-sodium and 84.4±3.1 kg on the higher-sodium diet in space and 87.1±3.6 kg on the lower-sodium and 87.2±3.2 kg on the higher-sodium diet on Earth (P=0.641). Natriuretic peptide and aldosterone responses to lower- and higher-sodium diets in space and on Earth are illustrated in the Figure. In space, MRproANP was 31.4±4.0 pmol/L (median [interquartile range], 31.1 pmol/L [25.3–40.1 pmol/L]) on the lower-sodium diet and 44.6±4.3 pmol/L (44.5 pmol/L [37.9-46.0 pmol/L]) on the higher-sodium diet (P<0.001). On Earth, MRproANP was 65.1±6.7 pmol/L (70.3 pmol/L [48.7–80.0 pmol/L]) on the lowersodium diet and 71.9±4.39 pmol/L (69.6 pmol/L [67.7– 75.2 pmol/L]) on the higher-sodium diet (P<0.001). Regardless of sodium intake, MRproANP was lower in space (P<0.001). The response of NT-proBNP to the change in sodium intake (P<0.001) was similar to that of MRproANP and was also regulated at lower levels in space than on Earth (P=0.008). In contrast, serum aldosterone concentrations were similarly regulated in space and on Earth (P=0.95 for space versus Earth, P<0.001 for lower- versus higher-sodium diet). Last, impedancebased thoracic fluid estimates were reduced in space to levels below those obtained during standing on Earth (P<0.001; Figure). A key finding from our study is that in space, although cardiac natriuretic peptide concentrations respond to changes in sodium intake, they are reset to lower levels. Reductions in thoracic blood volume may be causative, provided that impedance measurements were not confounded by changes in thoracic air content. In contrast, head-down bed rest elicited the opposite natriuretic peptide response.4 On Earth, cardiac natriuretic peptides and the renin-angiotensin-aldosterone axis are usually regulated in a reciprocal fashion, yet aldosterone regulation was virtually identical in space and on Earth. Given their importance in volume regulation, the question of whether resetting of natriuretic peptides in space reflects appropriate responses to reduced central blood volume or true natriuretic peptide deficiency deserves further studies.