Acute saline infusion induces extracellular acidification and activation of the Na+/H+ exchanger in man

The effect of acute expansion of the extracellular fluid volume (ECV) with isotonic (0.9%) saline on the activity of the lymphocyte Na⁺/H⁺ antiport (NHE) was studied in a total of 18 healthy volunteers. Saline was infused at a constant rate so that 4 mmol kg^?1 b.w. was administered over 2 h. NHE activity was measured by quantifying cytosolic pH (pH_i) recovery following acidification of the cells with propionic acid and by pH clamping at various pH_i values between 7.2 and 5.8 using nigericin. Both methods demonstrate NHE activation associated with intravenous saline infusion, the kinetic difference being a marked decrease in the Hill coefficient n from 3.28 ± 0.21 (SEM) to 2.22 ± 0.11 in the absence of changes in baseline pH_i (7.14 ± 0.02 vs. 7.08 ± 0.02; P = 0.15), V_max (42.8 ± 2.7 vs. 48.1 ± 2.8 mmol L^?1 min^?1; P = 0.08) and pK (6.32 ± 0.04 vs. 6.35 ± 0.02). NHE activation was associated with significant decreases in serum chloride (P = 0.016), calcium (P = 0.008), total cholesterol (P = 0.008), low-density lipoproteins (P = 0.016) and high-density lipoproteins (P = 0.008). Moreover, saline infusion induced extracellular acidification with a decrease in pH from 7.39 ± 0.01 to 7.37 ± 0.01 (P = 0.016), HCO₃^? from 23.3 ± 0.43 mmol L^?1 to 21.3 ± 0.25 mmol L^?1 (P = 0.008) and base excess from ?1.03 ± 0.38 mmol L^?1 to ?3.00 ± 0.31 mmol L^?1 (P = 0.008). Our results show for the first time that acute ECV expansion with isotonic saline is followed by an activation of the lymphocyte NHE. The underlying mechanism(s) remain to be investigated. However, the demonstration in our study of marked changes in acid–base balance induced by acute saline points to a possible inter-relationship of antiporter activation and extracellular acidification.