Osmotic and nonosmotic sodium storage during acute hypertonic sodium loading

Background: The Edelman equation has long guided the expected response of plasma [Na⁺] to changes in sodium, potassium, and water balance, but recent short-term studies challenged its validity. Plasma [Na⁺] following hypertonic NaCl infusion in individuals on low-sodium diet fell short of the Edelman predictions supposedly because sodium restriction caused progressive osmotic inactivation of 50% of retained sodium. Here, we examine the validity of this challenge. Methods: We evaluated baseline total body water (TBW) and Na⁺ space following acute hypertonic NaHCO₃ infusion in dogs with variable sodium and potassium stores, including normal stores, moderate depletion (chronic HCl feeding), or severe depletion (diuretics and dietary NaCl deprivation). Results: TBW (percentage body weight) averaged 65.9 in normals, 62.6 in HCl-induced metabolic acidosis and moderate sodium and potassium depletion, and 57.6 in diuretic-induced metabolic alkalosis and severe sodium and potassium depletion (p < 0.02). Na⁺ space (percentage body weight) at 30, 60, and 90 min postinfusion averaged 61.1, 59.8, and 56.1, respectively, in normals (p = 0.49); 70.0, 74.4, and 72.1, respectively, in acidotic animals (p = 0.21); and 56.4, 55.1, and 54.2, respectively, in alkalotic animals (p = 0.41). Absence of progressive expansion of Na⁺ space in each group disproves progressive osmotic inactivation of retained sodium. Na⁺ space at each time point was not significantly different from baseline TBW in normal and alkalotic animals indicating that retained sodium remained osmotically active in its entirety. However, Na⁺ space in acidotic animals at all times exceeded by ∼16% baseline TBW (p < 0.01) signifying an early, but nonprogressive, osmotic inactivation of retained sodium, which we link to baseline bone-sodium depletion incurred during acid buffering. Conclusions: Our investigation affirms the validity of the Edelman construct in normal dogs and dogs with variable sodium and potassium depletion and, consequently, refutes the recent observations in human volunteers subjected to dietary NaCl restriction.