Prenatal glucocorticoids stimulate neonatal juxtamedullary proximal convoluted tubule acidification

The rate of neonatal proximal convoluted tubule (PCT) HCO₃ absorption is lower than that of adult animals. The present in vitro microperfusion study examined whether prenatal dexamethasone (60 μg/kg daily to the doe for 3 days before delivery) would accelerate the maturation of neonatal juxtamedullary PCT acidification. Control neonates studied within 48 h of birth had a urine pH of 7.06 ± 0.15 and a urine HCO₃ concentration of 34.3 ± 7.0 meq/l. Animals receiving dexamethasone had a urine pH of 6.47 ± 0.11 and a urine HCO₃ concentration of 10.1 ± 4.0 meq/l, both of which were significantly lower than control (P < 0.01). In juxtamedullary PCTs perfused in vitro, volume absorption was 0.27 ± 0.03 nl·mm^-1·min^-1 in controls and 0.39 ± 0.02 nl·mm^-1·min^-1 in dexamethasone-treated animals (P < 0.05). HCO₃ absorption was stimulated in the dexamethasone group (52.6 ± 4.6 vs. 34.1 ± 6.3 pmol·mm^-1·min^-1, P < 0.05); however, glucose transport was not significantly affected (24.8 ± 1.3 in dexamethasone vs. 21.5 ± 3.5 pmol·mm^-1·min^-1 in controls). Intracellular pH was measured using 2',7'-bis(carboxyethyl)-5(6)-carboxyflourescein to examine whether prenatal dexamethasone stimulated the apical Na⁺-H⁺ antiporter and the basolateral Na(HCO₃)₃ symporter. Apical Na⁺-H⁺ antiporter proton flux was 108.5 ± 14.2 pmol·mm^-1.min^-1 in the control group and 250.7 ± 31.3 pmol·mm^-1·min^-1 in the dexamethasone group (P < 0.001). Basolateral Na(HCO₃)₃ symporter proton flux was 106.1 ± 10.0 pmol·mm^-1·min^-1 in control animals and 202.6 ± 17.8 pmol·mm^-1·min^-1 in the dexamethasone group (P < 0.001). Thus prenatal dexamethasone stimulates juxtamedullary PCT HCO₃ absorption in part by increasing apical Na⁺-H⁺ antiporter and basolateral Na(HCO₃)₃ symporter activity. These data are consistent with a role for glucocorticoids in proximal tubular maturation.