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.

Salty skin: Where excess sodium goes for a rendezvous

“…dermis) of the skin during high-salt conditions suggest that sodium deposition in the skin is highly compartmentalized. While excess sodium can be stored intra-and extracellularly, their additional findings of no change in sodium content in the skin interstitial fluid suggests the intracellular fluid compartment as a predominant sodium storage site (Thowsen et al, 2022). Furthermore, compared to LSD, sGAG concentration in the whole skin and dermis did not change in the HSD group and was lower in the DOCA group, suggesting that sGAGs were unaffected by high-salt conditions in this study (Thowsen et al, 2022).…”

“…has become increasingly recognized as a pivotal regulator of sodium balance and may ultimately play an important role in blood pressure regulation and CVD pathogenesis. Of particular interest is the recent study by Thowsen et al in The Journal of Physiology (Thowsen et al, 2022), which sought to investigate the role skin may play as an extra-renal mechanism in regulating blood pressure via sodium accumulation during high-salt conditions. Specifically, the skin interstitium may act as a reservoir to store osmotically inactive sodium without affecting water retention.…”

“…This may be, in part, due to the skin interstitium's high content of sulphated glycosaminoglycans (sGAGs), which are large negatively charged disaccharide chains. Thowsen et al (2022) tested the hypotheses that a sodium gradient in the skin was present with an increasing content towards the surface due to a counter-current mechanism and that sGAGs may be responsible for the osmotically inactive sodium accumulation. In this study, male Sprague-Dawley rats (11-15 weeks old) underwent either a high-salt diet (HSD) or deoxycorticosterone acetate (DOCA)-salt pellet implantation; rats on a low-salt diet (LSD) served as a control group.…”

“…Skin samples were used to investigate electrolyte concentrations, components of intracellular and extracellular matrices at various depths of the skin, and determine the presence of microscopic vascular loops (Thowsen et al, 2022). Skeletal and cardiac muscle tissues were used to determine intracellular (ICV), extracellular (ECV), and interstitial fluid volumes (Thowsen et al, 2022). Compared to LSD, sodium concentration, expressed in both dry and wet weights, increased in the whole skin and dermis, but not the epidermis, in both HSD and DOCA-salt groups.…”

“…exchanging sodium and potassium) in different fluid compartments of both skeletal and cardiac muscles that warrants further investigation. Though Thowsen et al (2022) provided important insight into various J Physiol 600.13 compartments (i.e. skin, skeletal muscle and cardiac muscle) by which excess sodium can be stored during high-salt conditions, several questions remain regarding mechanistic underpinnings and physiological consequences of sodium accumulation in the skin and other extrarenal tissues.…”