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-mu-g/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 PCTHCO3 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.