Tissue sodium storage: evidence for kidney-like extrarenal countercurrent systems?

Hofmeister, Lucas H.; Perisic, Stojan; Titze, Jens

doi:10.1007/s00424-014-1685-x

Cited by 59 publications

(67 citation statements)

References 34 publications

(48 reference statements)

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“…Interestingly, the urea concentration was higher in epidermis-dermis than in lower dermis in LSD, HSD, and DOCA-salt rats, being most pronounced in HSD ( Figure 6D), suggesting that urea apparently contributed to the observed osmolal gradient, and supporting the idea of countercurrent exchange in the skin. 20 Plasma urea was equivalent in LSD and HSD, both exceeding the concentration in DOCAsalt rats (P<0.01 for both comparisons; Figure 6E). …”

Section: Osmolyte and Electrolyte Gradients In Skinmentioning

confidence: 88%

“…Notwithstanding this finding, by elution, we were able to demonstrate that there was an osmolality and urea gradient from epidermis through dermis to subcutis. This gradient may reflect a proposed countercurrent mechanism for electrolyte homeostasis 20 and calls for a more refined analysis of osmolyte and electrolyte distribution in the various layers of skin.…”

Section: Discussionmentioning

confidence: 99%

“…20 We, therefore, eluted, in distilled H 2 O, skin samples separated into epidermis-upper dermis (upper 0.5 mm) and lower dermis (subsequent 0.5 mm) with the tissue slicer as described for the punch biopsies. That the latter sample type did not include subcutaneous fat was shown by regular hematoxylin-eosin-stained histological sections of back skin from 2 rats.…”

Section: Osmolyte and Electrolyte Gradients In Skinmentioning

confidence: 99%

“…31 Interestingly, this Na + accumulation was not associated with a significant volume increase in the same area as would have been expected if the Na + exerted at least some of its crystalloid osmotic effect. The apparent conundrum of skin Na + gradients and lack of corresponding fluid accumulation led Hofmeister et al 20 to suggest that there is a functional countercurrent mechanism that enables the skin to differentially control its own microenvironment. Our data showing an epidermal to dermal osmolyte gradient that also includes urea and is increased in salt accumulation supports the hypothesis.…”

Section: Osmolyte and Electrolyte Gradients In Skin And Implications mentioning

confidence: 99%

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High-Salt Diet Causes Osmotic Gradients and Hyperosmolality in Skin Without Affecting Interstitial Fluid and Lymph

et al. 2017

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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...

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Section: Osmolyte and Electrolyte Gradients In Skinmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Osmolyte and Electrolyte Gradients In Skinmentioning

confidence: 99%

Section: Osmolyte and Electrolyte Gradients In Skin And Implications mentioning

confidence: 99%

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High-Salt Diet Causes Osmotic Gradients and Hyperosmolality in Skin Without Affecting Interstitial Fluid and Lymph

et al. 2017

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“…Furthermore, active Na + transport by keratinocytes may create an additional physiological fluid barrier with high osmolality inside or directly under the epidermis (Hofmeister et al, 2015; Warner et al, 1988). High magnetic strength (7 Tesla) 23 Na MRI analyses have confirmed the existence of this Na + -rich fluid layer in the human skin (Linz et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Cutaneous Na+ Storage Strengthens the Antimicrobial Barrier Function of the Skin and Boosts Macrophage-Driven Host Defense

et al. 2015

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Summary Immune cells regulate a hypertonic microenvironment in the skin; however, the biological advantage of increased skin Na+ concentrations is unknown. We found that Na+ accumulated at the site of bacterial skin infections in humans and in mice. We used the protozoan parasite Leishmania major as a model of skin-prone macrophage infection to test the hypothesis that skin-Na+ storage facilitates antimicrobial host defense. Activation of macrophages in the presence of high NaCl concentrations modified epigenetic markers and enhanced p38 mitogen-activated protein kinase (p38/MAPK)-dependent nuclear factor of activated T cells 5 (NFAT5) activation. This high-salt response resulted in elevated type-2 nitric oxide synthase (Nos2)-dependent NO production and improved Leishmania major control. Finally, we found that increasing Na+ content in the skin by a high-salt diet boosted activation of macrophages in an Nfat5-dependent manner and promoted cutaneous antimicrobial defense. We suggest that the hypertonic microenvironment could serve as a barrier to infection.

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Myeloid cells, tissue homeostasis, and anatomical barriers as innate immune effectors in arterial hypertension

Wild

Wenzel

2021

J Mol Med

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Although essential hypertension affects a large proportion of the human population and is one of the key drivers of cardiovascular mortality worldwide, we still do not have a complete understanding of its pathophysiology. More than 50 years ago, the immune system has been identified as an important part of the pathogenesis of arterial hypertension. An exceeding variety of recent publications deals with the interplay between the numerous different components of the immune system and mechanisms of arterial hypertension and has substantially contributed to our understanding of the role of immunity and inflammation in the pathogenesis of the disease. In this review, we focus on myeloid cells and anatomical barriers as particular aspects of innate immunity in arterial hypertension. Since it represents a first line of defense protecting against pathogens and maintaining tissue homeostasis, innate immunity provides many mechanistic hinge points in the area of hypertension.

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Tissue sodium storage: evidence for kidney-like extrarenal countercurrent systems?

Cited by 59 publications

References 34 publications

High-Salt Diet Causes Osmotic Gradients and Hyperosmolality in Skin Without Affecting Interstitial Fluid and Lymph

High-Salt Diet Causes Osmotic Gradients and Hyperosmolality in Skin Without Affecting Interstitial Fluid and Lymph

Cutaneous Na+ Storage Strengthens the Antimicrobial Barrier Function of the Skin and Boosts Macrophage-Driven Host Defense

Myeloid cells, tissue homeostasis, and anatomical barriers as innate immune effectors in arterial hypertension

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