Natriuretic Peptide Resetting in Astronauts
Petra Frings‐Meuthen, Elena Luchitskaya, Jens Jordan, Jens Tank, Ralf Lichtinghagen, Scott M. Smith, Martina Heer
Abstract
When astronauts enter weightlessness, cephalad fluid shifts increase left ventricular dimensions, whereas central venous pressure is surprisingly reduced. More chronically, counterregulatory adjustments attenuate \ntotal blood volume; however, the internal jugular vein remains grossly dilated.1 \nThis finding would raise suspicion for central volume overload in terrestrial medicine. Moreover, a single astronaut retained substantial amounts of sodium in space \nwithout 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 \nsimilar to those in weightlessness, elicited sustained increases in circulating atrial \nnatriuretic peptide concentrations.4 Conversely, individual astronauts have shown \nreduced natriuretic peptide signalling in space.5 Cardiac natriuretic peptide deficiency could exacerbate central hypervolemia. We assessed natriuretic peptides in \nastronauts in the first study comparing lower-sodium and higher-sodium diets in \nspace and on Earth. \nThe SOLO study (Sodium Load in Microgravity) was approved by the Johnson \nSpace Center institutional review board and the European Space Agency medical \nboard. After giving informed consent, we tested 8 male astronauts (50±2.8 years \nold; weight, 85.61±8.89 kg) on both lower-sodium (2 g/d) and higher-sodium (5.5 \ng/d) diets for 5 consecutive days in space and 6 to 12 months after landing on \nEarth. In space, diets were applied in random order no earlier than 4 weeks into \nthe mission. Dietary nutrient and water intakes were kept constant. Blood samples \nwere obtained on day 5 of each intervention and analyzed for sodium, creatinine, midregional proatrial natriuretic peptide (MRproANP), NT-proBNP (N-terminal \npro-B-type natriuretic peptide), and aldosterone. On Earth, samples were obtained \nwhile subjects were seated in the morning after they had traveled from the hotel \nto the study center. The same day, urinary sodium, creatinine, and body mass were \nmeasured. Body mass on the International Space Station was measured with the \nNational Aeronautics and Space Administration’s Space Linear Acceleration Mass \nMeasurement Device; on Earth, we used a standard scale. \nTo gauge changes in central blood volume, we assessed thoracic bioimpedance \nin 16 cosmonauts (45.56±5.59 years old; weight, 79.88±6.94 kg) before launch, \nmonthly onboard the International Space Station, and after return to Earth. The \nstudy in cosmonauts was approved by the Biomedicine Ethics Committee of the \nState Research Center of the Russian Federation, the Institute of Biomedical Problems, the Russian Academy of Science, and the subjects gave informed consent. \nOn the lower-sodium diet, astronauts excreted 74.3±7.0 mmol of sodium per \nday (mean+SEM) in space and 82.6±10.3 mmol/d on Earth (P=0.172). On the \nhigher-sodium diet, astronauts excreted 175±12 mmol/d in space and 196±13 \nmmol/d on Earth (P=0.249). Glomerular filtration rate was unchanged, whereas fractional sodium excretion increased similarly on the \nhigher-sodium diet (P<0.001) in space and on Earth. \nBody mass was 83.7±3.1 kg on the lower-sodium and \n84.4±3.1 kg on the higher-sodium diet in space and \n87.1±3.6 kg on the lower-sodium and 87.2±3.2 kg on \nthe 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 \nthe Figure. In space, MRproANP was 31.4±4.0 pmol/L \n(median [interquartile range], 31.1 pmol/L [25.3–40.1 \npmol/L]) on the lower-sodium diet and 44.6±4.3 pmol/L \n(44.5 pmol/L [37.9-46.0 pmol/L]) on the higher-sodium \ndiet (P<0.001). On Earth, MRproANP was 65.1±6.7 \npmol/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– \n75.2 pmol/L]) on the higher-sodium diet (P<0.001). \nRegardless of sodium intake, MRproANP was lower \nin space (P<0.001). The response of NT-proBNP to the \nchange in sodium intake (P<0.001) was similar to that \nof MRproANP and was also regulated at lower levels in \nspace than on Earth (P=0.008). In contrast, serum aldosterone concentrations were similarly regulated in space \nand on Earth (P=0.95 for space versus Earth, P<0.001 \nfor lower- versus higher-sodium diet). Last, impedancebased thoracic fluid estimates were reduced in space to \nlevels below those obtained during standing on Earth \n(P<0.001; Figure). \nA key finding from our study is that in space, although cardiac natriuretic peptide concentrations respond to changes in sodium intake, they are reset to \nlower levels. Reductions in thoracic blood volume may \nbe causative, provided that impedance measurements \nwere not confounded by changes in thoracic air content. In contrast, head-down bed rest elicited the opposite natriuretic peptide response.4 On Earth, cardiac \nnatriuretic peptides and the renin-angiotensin-aldosterone axis are usually regulated in a reciprocal fashion, \nyet aldosterone regulation was virtually identical in \nspace and on Earth. Given their importance in volume \nregulation, the question of whether resetting of natriuretic peptides in space reflects appropriate responses \nto reduced central blood volume or true natriuretic \npeptide deficiency deserves further studies.