Tissue sodium excess is not hypertonic and reflects extracellular volume expansion
Giacomo Rossitto, Sheon Mary, Jun Yu Chen, Philipp Boder, Khai Syuen Chew, Karla B Neves, Rhéure Alves-Lopes, Augusto C. Montezano, Paul Welsh, Mark C. Petrie, Delyth Graham, Rhian M. Touyz, Christian Delles
Abstract
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.