Mobilization of osmotically inactive Na⁺ by growth and by dietary salt restriction in rats

Abstract

The idea that an osmotically inactive Na(+) storage pool exists that can be varied to accommodate states of Na(+) retention and/or Na(+) loss is controversial. We speculated that considerable amounts of osmotically inactive Na(+) are lost with growth and that additional dietary salt excess or salt deficit alters the polyanionic character of extracellular glycosaminoglycans in osmotically inactive Na(+) reservoirs. Six-week-old Sprague-Dawley rats were fed low-salt (0.1%; LS) or high-salt (8%; HS) diets for 1 or 4 wk. At their death, we separated the tissues and determined their Na(+), K(+), and water content. Three weeks of growth reduced the total body Na(+) content relative to dry weight (rTBNa(+)) by 23%. This "growth-programmed" Na(+) loss originated from the bone and the completely skinned and bone-removed carcasses. The Na(+) loss was osmotically inactive (45-50%) or osmotically active (50-55%). In rats aged 10 wk, compared with HS, 4 wk of LS reduced rTBNa(+) by 9%. This dietary-induced Na(+) loss was osmotically inactive ( approximately 50%) and originated largely from the skin, while approximately 50% was osmotically active. LS for 1 wk did not reduce skin Na(+) content. The mobilization of osmotically inactive skin Na(+) with long-term salt deprivation was associated with decreased negatively charged skin glycosaminoglycan content and thereby a decreased water-free Na(+) binding capacity in the extracellular matrix. Our data not only serve to explain discrepant results in salt balance studies but also show that glycosaminoglycans may provide an actively regulated interstitial cation exchange mechanism that participates in volume and blood pressure homeostasis.

Immune cells control skin lymphatic electrolyte homeostasis and blood pressure

“…Along with others (4-7), we (8)(9)(10)(11)(12)(13)(14) showed earlier that electrolytes are distributed in a more complex 3-compartment model, in which intravascular and the interstitial fluids do not equilibrate as readily as believed (15,16). We underscored the importance of Na + binding to negatively charged proteoglycans in the skin, the largest organ with the most extracellular space (8,11). We suggested that, in addition to renal control, local extrarenal regulatory mechanisms for electrolyte clearance of interstitial fluid are operative to maintain extracellular electrolyte clearance and blood pressure.…”

Interstitial Fluid and Lymph Formation and Transport: Physiological Regulation and Roles in Inflammation and Cancer

“…They first showed that Na ϩ retention during high salt feeding was associated with increasing GAG content in cartilage and skin (468). Then, they measured osmotically active and inactive Na ϩ (i.e., Na ϩ accumulation without corresponding accumulation of water) during growth of rats on a low-(0.1%) vs. high-salt (8%) diet (412) and found that while salt was lost from the body during growth, there was additionally a dietary-induced salt loss of osmotically inactive Na ϩ that originated mostly from skin. Long-term salt deprivation resulted in a shift of PG composition with reduced sulfated PGs and increased hyaluronan, which lowered the charge density and water-free Na ϩ binding to the ECM.…”

Mononuclear Phagocyte System Depletion Blocks Interstitial Tonicity-Responsive Enhancer Binding Protein/Vascular Endothelial Growth Factor C Expression and Induces Salt-Sensitive Hypertension in Rats

“…Chemical analysis of the carcasses included Na ϩ , K ϩ , Cl Ϫ , and water measurements after dry ashing of the different tissues as reported previously. 8,10 We calculated the Cl Ϫ space as a measure of the extracellular volume from the tissue Cl Ϫ content and the serum Cl Ϫ concentration. The Cl Ϫ -free water space was calculated as a measure of the intracellular volume.…”