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.
Highlights
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
Our study offers a reappraisal of the tissue Na+ theory, disproves its water-independence in both experimental salt-sensitive hypertension and hypertensive subjects and suggests systemic isotonic (IT) Na+ excess as an important player in the pathogenesis of cardiovascular disease, in association with the process of aging
Baseline blood pressure (BP) was higher, irrespective of strain differences, and salt sensitivity of BP was confined to SHRSPs (Supplementary Fig. 1)
Summary
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. Excess Na+ accumulation upon salt loading, with some sex specificities, was found in healthy subjects by direct skin chemical analysis[21] Both methods measure Na+ in the whole tissue. TonEBP-mediated signalling while simultaneously eluding parallel and commensurate water accrual, appears equivocal On these premises, we sought to test the existence, distribution and putative correlates of HT tissue Na+ accumulation by probative and disprobative approaches (i.e., by verifying and by assuming its occurrence, respectively) in preclinical models of and real-life patients with arterial hypertension. Our study offers a reappraisal of the tissue Na+ theory, disproves its water-independence in both experimental salt-sensitive hypertension and hypertensive subjects and suggests systemic isotonic (IT) Na+ excess as an important player in the pathogenesis of cardiovascular disease, in association with the process of aging
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