A commonly accepted core mechanism in fluid volume and blood pressure regulation is the parallel relationship between body Na + and extracellular fluid content. 1 It is assumed that Na + readily equilibrates between the intravascular and interstitial compartments that together constitute the extracellular fluid and that Na + concentrations are not remarkably different between the interstitial and intravascular volume. This idea is based on the relatively simple physicochemical concept of passive body fluid equilibrium in closed systems. 2 To maintain blood pressure homeostasis, body fluid volume and thereby body Na + content has to be maintained within narrow limits.In long-term observations in humans, however, several studies have shown that considerable amounts of Na + are retained or removed from the subjects' bodies without commensurate water retention or loss. [3][4][5][6] This finding suggests that Na + could be stored somewhere in the body without commensurate water retention and thereby be inactive from a fluid balance viewpoint. 7 Previously unidentified extrarenal, tissue-specific regulatory mechanisms that control the release and storage of Na + from a kidney-independent reservoir are a requirement in this scenario, thereby questioning the usual notion of a 2-compartment model. 2 Later studies have indicated that skin might serve as major Na + reservoir. [8][9][10] An implication of these observations might be that there is not a strict isotonicity of all body fluids and that skin electrolyte concentrations do not necessarily equilibrate with blood electrolytes.One consequence of such electrolyte accumulation in excess of water would be that it might cause local hypertonicity. Indeed, using vapor pressure osmometry, we recently demonstrated that Na + accumulation in skin as a consequence of feeding the rats a high-salt diet (HSD) results in a tissue that is hyperosmotic relative to plasma.11 Supporting this notion, interstitial fluid (IF) sampled by microdialysis was found to be ≈10 mosmol/kg, and the Na + concentration in tissue regions presumed to be lymphatics ≈20 mmol/L higher than plasma. 11Such electrolyte gradients would, even with a low capillary reflection coefficient, represent formidable transcapillary forces that would favor massive edema formation. Because the fluid accumulation in rats where salt accumulation has been induced by HSD and deoxycorticosterone acetate (DOCA) combined Abstract-The common notion is that the body Na + is maintained within narrow limits for fluid and blood pressure homeostasis. Several studies have, however, shown that considerable amounts of Na + can be retained or removed from the body without commensurate water loss and that the skin can serve as a major salt reservoir. Our own data from rats have suggested that the skin is hypertonic compared with plasma on salt storage and that this also applies to skin interstitial fluid. Even small electrolyte gradients between plasma and interstitial fluid would represent strong edema-generating forces. Because the...

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.