The serum
bicarbonate in neonates is lower than adults due in large part to a lower rate of proximal tubule acidification. It is unclear if the neonatal proximal tubule is functioning at maximal capacity or if the proximal tubule can respond to
metabolic acidosis as has been described in adult proximal tubules. We find that neonatal mouse brush-border membranes have a lower
Na(+)/H(+) exchanger (
NHE) 3 protein abundance (neonate 0.11 ± 0.05 vs. adult 0.64 ± 0.07; P < 0.05) and a higher NHE8
protein abundance (neonate 1.0 ± 0.01 vs. adult 0.13 ± 0.09; P < 0.001) compared with adults. To examine if neonates can adapt to
acidosis, neonatal mice were gavaged with either
acid or vehicle for 4 days, resulting in a drop in serum
bicarbonate from 19.5 ± 1.0 to 8.9 ± 0.6 meq/l (P < 0.001). Proximal convoluted tubule
Na(+)/H(+) exchanger activity (dpH(i)/dt) was 1.68 ± 0.19 pH units/min in control tubules and 2.49 ± 0.60 pH units/min in acidemic neonatal mice (P < 0.05), indicating that the neonatal proximal tubule can respond to
metabolic acidosis with an increase in
Na(+)/H(+) exchanger activity. Similarly, brush-border membrane vesicles from neonatal rats had an increase in
Na(+)/H(+) exchanger activity with acidemia that was almost totally inhibited by 10(-6) M 5-(N-ethyl-n-isopropyl)-amiloride, a dose that has little effect on NHE3 but inhibits NHE8. There was a significant increase in both NHE3 (vehicle 0.35 ± 0.07 vs.
acid 0.73 ± 0.07; P < 0.003) and NHE8 brush-border
membrane protein abundance (vehicle 0.41 ± 0.05 vs.
acid 0.73 ± 0.06; P < 0.001) in acidemic mouse neonates compared with controls. A comparable increase in NHE3 and NHE8 was found in neonatal rats with
acidosis. In conclusion, the neonatal proximal tubule can adapt to
metabolic acidosis with an increase in
Na(+)/H(+) exchanger activity.