Kitada, Kento and Daub, Steffen and Zhang, Yahua and Klein, Janet D. and Nakano, Daisuke and Pedchenko, Tetyana and Lantier, Louise and LaRocque, Lauren M. and Marton, Adriana and Neubert, Patrick and Schroeder, Agnes and Rakova, Natalia and Jantsch, Jonathan and Dikalova, Anna E. and Dikalov, Sergey I. and Harrison, David G. and Mueller, Dominik N. and Nishiyama, Akira and Rauh, Manfred and Harris, Raymond C. and Luft, Friedrich C. and Wassermann, David H. and Sands, Jeff M. and Titze, Jens (2017) High salt intake reprioritizes osmolyte and energy metabolism for body fluid conservation. JOURNAL OF CLINICAL INVESTIGATION, 127 (5). pp. 1944-1959. ISSN 0021-9738, 1558-8238
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ACTIVATED PROTEIN-KINASE; ACETYL-COA CARBOXYLASE; AMINO-ACID-METABOLISM; AFRICAN LUNGFISH; UREA TRANSPORTER; IN-VIVO; PROTOPTERUS-AETHIOPICUS; PROLONGED STARVATION; RAT MUSCLE; ESTIVATION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 13:10 |
| Last Modified: | 28 Feb 2019 10:34 |
| URI: | https://pred.uni-regensburg.de/id/eprint/985 |
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