Na⁺ is shifted from the extracellular to the intracellular compartment and is not inactivated by glycosaminoglycans during high salt conditions in rats

Abstract: Recently, studies have emerged suggesting that the skin plays a role as major Na⁺ reservoir via regulation of the content of glycosaminoglycans and osmotic gradients. We investigated whether there were electrolyte gradients in skin and where Na⁺ could be stored to be inactivated from a fluid balance viewpoint. Na⁺ accumulation was induced in rats by a high salt diet (HSD) (8% NaCl and 1% saline to drink) or by implantation of a deoxycorticosterone acetate (DOCA) tablet (1% saline to drink) using rats on a low salt diet (LSD) (0.1% NaCl) on tap water as control. Na⁺ and K⁺ were assessed by ion chromatography in tissue eluates, and the extracellular volume by equilibration of ⁵¹Cr-EDTA. By tangential sectioning of the skin, we found a low Na⁺ content and extracellular volume in epidermis, both parameters rising by ∼30% and 100%, respectively, in LSD and even more in HSD and DOCA when entering dermis. We found evidence for an extracellular Na⁺ gradient from epidermis to dermis shown by an estimated concentration in epidermis ∼2 and 4–5 times that of dermis in HSD and DOCA-salt. There was intracellular storage of Na⁺ in skin, muscle, and myocardium without a concomitant increase in hydration. Our data suggest that there is a hydration-dependent high interstitial fluid Na⁺ concentration that will contribute to the skin barrier and thus be a mechanism for limiting water loss. Salt stress results in intracellular storage of Na⁺ in exchange with K⁺ in skeletal muscle and myocardium that may have electromechanical consequences. Key points: Studies have suggested that Na⁺ can be retained or removed without commensurate water retention or loss, and that the skin plays a role as major Na⁺ reservoir via regulation of the content of glycosaminoglycans and osmotic gradients. In the present study, we investigated whether there were electrolyte gradients in skin and where Na⁺ could be stored to be inactivated from a fluid balance viewpoint. We used two common models for salt-sensitive hypertension: high salt and a deoxycorticosterone salt diet. We found a hydration-dependent high interstitial fluid Na⁺ concentration that will contribute to the skin barrier and thus be a mechanism for limiting water loss. There was intracellular Na⁺ storage in muscle and myocardium without a concomitant increase in hydration, comprising storage that may have electromechanical consequences in salt stress.