High salt intake reprioritizes osmolyte and energy metabolism for body fluid
Authors Kitada K, Daub S, Zhang Y, Klein JD, Nakano D, Pedchenko T, Lantier L, LaRocque
LM, Marton A, Neubert P, Schroder A, Rakova N, Jantsch J, Dikalova AE, Dikalov
SI, Harrison DG, Müller DN, Nishiyama A, Rauh M, Harris RC, Luft FC, Wassermann
DH, Sands JM, Titze J
Submitted By Submitted Externally on 5/23/2017
Status Published
Journal The Journal of clinical investigation
Year 2017
Date Published 5/1/2017
Volume : Pages 127 : 1944 - 1959
PubMed Reference 28414295
Abstract Natriuretic regulation of extracellular fluid volume homeostasis includes
suppression of the renin-angiotensin-aldosterone system, pressure natriuresis,
and reduced renal nerve activity, actions that concomitantly increase urinary
Na+ excretion and lead to increased urine volume. The resulting
natriuresis-driven diuretic water loss is assumed to control the extracellular
volume. Here, we have demonstrated that urine concentration, and therefore
regulation of water conservation, is an important control system for urine
formation and extracellular volume homeostasis in mice and humans across various
levels of salt intake. We observed that the renal concentration mechanism
couples natriuresis with correspondent renal water reabsorption, limits
natriuretic osmotic diuresis, and results in concurrent extracellular volume
conservation and concentration of salt excreted into urine. This
water-conserving mechanism of dietary salt excretion relies on urea
transporter-driven urea recycling by the kidneys and on urea production by liver
and skeletal muscle. The energy-intense nature of hepatic and extrahepatic urea
osmolyte production for renal water conservation requires reprioritization of
energy and substrate metabolism in liver and skeletal muscle, resulting in
hepatic ketogenesis and glucocorticoid-driven muscle catabolism, which are
prevented by increasing food intake. This natriuretic-ureotelic,
water-conserving principle relies on metabolism-driven extracellular volume
control and is regulated by concerted liver, muscle, and renal actions.