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+ a ntiport (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 administ ered over 2 h. NHE activity was measured by quantifying cytosolic pH ( pH(i)) recovery following acidification of the cells with propionic ac id and by pH clamping at various pH(i) values between 7.2 and 5.8 usin g nigericin. Both methods demonstrate NHE activation associated with i ntravenous saline infusion, the kinetic difference bring a marked decr ease 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 mi n(-1); P = 0.08) and pK (6.32 +/- 0.04 vs. 6.35 +/- 0.02). NHE activat ion was associated with significant cant decreases in serum chloride ( P = 0.016), calcium (P = 0.008), total cholesterol (P = 0.008), low-de nsity lipoproteins (P = 0.016) and high-density lipoproteins (P = 0.00 8). Moreover, saline infusion induced extracellular acidification with a decrease in pH from 7.39 +/- 0.01 to 7.37 +/- 0.01 (P = 0.016), HCO 3- from 23.3 +/- 0.43 mmol L-1 to 21.3 +/- 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 expansi on 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 an tiporter activation and extracellular acidification.