Dietary sodium induces a redistribution of the tubular metabolic workload.

Body Na <sup>+</sup> content is tightly controlled by regulated urinary Na <sup>+</sup> excretion. The intrarenal mechanisms mediating adaptation to variations in dietary Na <sup>+</sup> intake are incompletely characterized. We confirmed and expanded observations in mice that variations in dietary Na <sup>+</sup> intake do not alter the glomerular filtration rate but alter the total and cell-surface expression of major Na <sup>+</sup> transporters all along the kidney tubule. Low dietary Na <sup>+</sup> intake increased Na <sup>+</sup> reabsorption in the proximal tubule and decreased it in more distal kidney tubule segments. High dietary Na <sup>+</sup> intake decreased Na <sup>+</sup> reabsorption in the proximal tubule and increased it in distal segments with lower energetic efficiency. The abundance of apical transporters and Na <sup>+</sup> delivery are the main determinants of Na <sup>+</sup> reabsorption along the kidney tubule. Tubular O <sub>2</sub> consumption and the efficiency of sodium reabsorption are dependent on sodium diet. Na <sup>+</sup> excretion by the kidney varies according to dietary Na <sup>+</sup> intake. We undertook a systematic study of the effects of dietary salt intake on glomerular filtration rate (GFR) and tubular Na <sup>+</sup> reabsorption. We examined the renal adaptive response in mice subjected to 7 days of a low sodium diet (LSD) containing 0.01% Na <sup>+</sup> , a normal sodium diet (NSD) containing 0.18% Na <sup>+</sup> and a moderately high sodium diet (HSD) containing 1.25% Na <sup>+</sup> . As expected, LSD did not alter measured GFR and increased the abundance of total and cell-surface NHE3, NKCC2, NCC, α-ENaC and cleaved γ-ENaC compared to NSD. Mathematical modelling predicted that tubular Na <sup>+</sup> reabsorption increased in the proximal tubule but decreased in the distal nephron because of diminished Na <sup>+</sup> delivery. This prediction was confirmed by the natriuretic response to diuretics targeting the thick ascending limb, the distal convoluted tubule or the collecting system. On the other hand, HSD did not alter measured GFR but decreased the abundance of the aforementioned transporters compared to NSD. Mathematical modelling predicted that tubular Na <sup>+</sup> reabsorption decreased in the proximal tubule but increased in distal segments with lower transport efficiency with respect to O <sub>2</sub> consumption. This prediction was confirmed by the natriuretic response to diuretics. The activity of the metabolic sensor adenosine monophosphate-activated protein kinase (AMPK) was related to the changes in tubular Na <sup>+</sup> reabsorption. Our data show that fractional Na <sup>+</sup> reabsorption is distributed differently according to dietary Na <sup>+</sup> intake and induces changes in tubular O <sub>2</sub> consumption and sodium transport efficiency

Technical Design Report for the: PANDA Micro Vertex Detector

This document illustrates the technical layout and the expected performance of the Micro Vertex Detector (MVD) of the PANDA experiment. The MVD will detect charged particles as close as possible to the interaction zone. Design criteria and the optimisation process as well as the technical solutions chosen are discussed and the results of this process are subjected to extensive Monte Carlo physics studies. The route towards realisation of the detector is outlined.Comment: 189 pages, 225 figures, 41 table