Tissue sodium excess is not hypertonic and reflects extracellular volume expansion

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Rossitto, Giacomo and Mary, Sheon and Chen, Jun Yu and Boder, Philipp and Chew, Khai Syuen and Neves, Karla B. and Alves, Rheure L. and Montezano, Augusto C. and Welsh, Paul and Petrie, Mark C. and Graham, Delyth and Touyz, Rhian M. and Delles, Christian (2020) Tissue sodium excess is not hypertonic and reflects extracellular volume expansion. Nature Communications, 11 (1). 4222. ISSN 2041-1723 (https://doi.org/10.1038/s41467-020-17820-2)

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Abstract

Our understanding of Na+ homeostasis has recently been reshaped by the notion of skin as a depot for Na+ accumulation in multiple cardiovascular diseases and risk factors. The proposed water-independent nature of tissue Na+ could induce local pathogenic changes, but lacks firm demonstration. Here, we show that tissue Na+ excess upon high Na+ intake is a systemic, rather than skin-specific, phenomenon reflecting architectural changes, i.e. a shift in the extracellular-to-intracellular compartments, due to a reduction of the intracellular or accumulation of water-paralleled Na+ in the extracellular space. We also demonstrate that this accumulation is unlikely to justify the observed development of experimental hypertension if it were water-independent. Finally, we show that this isotonic skin Na+ excess, reflecting subclinical oedema, occurs in hypertensive patients and in association with aging. The implications of our findings, questioning previous assumptions but also reinforcing the importance of tissue Na+ excess, are both mechanistic and clinical.

ORCID iDs

Rossitto, Giacomo, Mary, Sheon, Chen, Jun Yu, Boder, Philipp, Chew, Khai Syuen, Neves, Karla B. ORCID logoORCID: https://orcid.org/0000-0001-5158-9263, Alves, Rheure L., Montezano, Augusto C., Welsh, Paul, Petrie, Mark C., Graham, Delyth, Touyz, Rhian M. and Delles, Christian;
CORE (COnnecting REpositories)