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

Abstract

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 (pHi) recovery following acidification of the cells with propionic acid and by pH clamping at various pHi 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 pHi (7.14 +/- 0.02 vs. 7.08 +/- 0.02; P = 0.15), Vmax (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.

Increased tolerance to hypoxic metabolic inhibition and reoxygenation of cardiomyocytes from apolipoprotein E-deficient mice

“…However, with downregulated and potentially inhibited NHE1, one would expect a more severe intracellular acidosis in myocytes from ApoE Ϫ/Ϫ mice during simulated ischemia as NHE1 removes intracellular H ϩ in exchange for extracellular Na ϩ . Contrary to this expectation, acidosis was attenuated in this study, which may primarily be explained by the fact that the cells were superfused with an acidic Tyrode solution during hypoxic metabolic inhibition that provokes reverse-mode activity of the NHE1 just as during metabolic acidosis (21). Additional pH-regulating mechanisms transmitted via the Na ϩ /HCO 3 Ϫ symporter and the Cl Ϫ /HCO 3 Ϫ antiporter, although not studied here, could also have contributed to the pH changes we determined in the course of simulated ischemia.…”

High sodium chloride intake exacerbates immobilization-induced bone resorption and protein losses

“…But still other possible mechanisms may be involved, as previously mentioned (25). Enforced activity of cellular Na ϩ /H ϩ exchangers (18,36) as well as Na ϩ /H ϩ ion exchanges on the extracellular glycosaminoglycans (19) and/or a Na-induced expansion of extracellular volume, resulting in a decrease in HCO 3 Ϫ reabsorption (3,38,52,58), can contribute to mediation of the effect of NaCl on acid-base balance. Summarizing, with high NaCl intake, renal loss of bicarbonate but also excess acid production could be reasonably expected to affect acid-base status.…”

Low-Grade Metabolic Acidosis May Be the Cause of Sodium Chloride–Induced Exaggerated Bone Resorption

“…Furthermore, the reason for the decreased pH and bicarbonate concentration could not be an addition of metabolic acids by ingestion or infusion of acids, because the subjects' intake of acid‐inducing foods was not higher during high salt intake. Studies from Dusing et al and Kessler et al have shown significant stimulation of the Na + /H + exchanger during acute saline (0.9%) infusion accompanied by cytosolic alkalinization and extracellular acidification and accomplished by decreases in pH, bicarbonate, and base excess.…”