Postnatal glucocorticoids induce α-ENaC formation and regulate glucocorticoid receptors in the preterm rabbit lung

Abstract

At birth, lung fluid clearance is coupled to Na+ transport through epithelial Na+ channels (ENaC) in the distal lung epithelium. We evaluated the effect of postnatal glucocorticoids (GC) on lung α-ENaC expression in preterm 29-day gestational age (GA) fetal rabbits. Postnatal treatment of 29-day GA fetuses with 0.5 mg/kg of dexamethasone (Dex) iv resulted in a 2- and 22-fold increase in lung α-ENaC mRNA expression compared with saline-treated fetuses after 8 and 16 h, respectively. Lung α-ENaC protein levels in Dex-treated fetuses were also elevated compared with saline-treated counterparts. The extravascular lung water (EVLW)/dry lung tissue weight ratios of 29-day GA fetuses treated with either saline or Dex decreased over 24 h compared with that observed at birth; however, at 24 h, the EVLW/dry lung tissue weight ratios of saline- and Dex-treated fetuses were similar. Dex-induced α-ENaC mRNA and protein levels were attenuated by glucocorticoid receptor (GCR) antagonist RU-486 in fetal distal lung epithelial cells isolated from 29-day GA fetuses, indicating that GC-dependent augmentation of lung α-ENaC requires the presence of functional GCR. Lung GCR mRNA expression and protein levels were elevated in 29-day GA fetuses compared with fetuses at earlier GA. Exposure of 29-day GA fetuses to Dex for 16 h caused a 2.1-fold increase in lung GCR mRNA expression, but GCR protein levels were decreased in Dex-treated fetuses after 24 h. We conclude that postnatal treatment of preterm 29-day GA fetal rabbits with GC results in an elevation of lung α-ENaC accompanied by an autoregulation of pulmonary GCR.

Effect of Maternal Administration of Betamethasone on Peripheral Arterial Development in Fetal Rabbit Lungs

“…A dose-effect relationship on lung and body weight has also been described earlier [2] . It is possible that the administered steroids mediate their effect on wet lung weight through decreased lung liquid production and/or reabsorption of lung liquid, as earlier documented in humans and rabbits [25,37] . In the experiments of Tabor et al [3] , doses of 0.01, 0.03 and 0.1 mg/kg were compared, with the highest dose showing the most obvious effects.…”

Ibuprofen-Induced Patent Ductus Arteriosus Closure: Physiologic, Histologic, and Biochemical Effects on the Premature Lung

“…14 Wet/Dry Ratio An aliquot of tissue from the right middle lobe was desiccated and used to calculate the wet weight/dry weight ratio. 15,16 Western Analysis for ␣-ENaC A piece of the right middle lobe was homogenized in lysis buffer, and Western blotting for ␣-ENaC protein was performed with an affinity-purified chicken polyclonal antibody raised against peptides corresponding to the NH 2 -terminal 22 amino acid residues of the rabbit ␣-ENaC protein (Affinity BioReagents, Golden, CO), as described previously. 16 Bronchoalveolar Lavage for Measurement of Saturated Phoshatidylcholine, Total Protein, Surfactant Proteins, and Cytokines/Chemokines At necropsy, bronchoalveolar lavage of the left lower lobe was performed with 0.9% NaCl solution.…”

Elective Cesarean Section: Its Impact on Neonatal Respiratory Outcome

“…31,52,68 Key factors in the lung "microenvironment" are steroids, catecholamines, and oxygen. 45,70,98,126 Of these factors, based on our animal data and human data from previous studies dealing with preterm gestations, it appears that the most effective strategy for accelerating reabsorption of fetal lung fluid would be the administration of exogenous glucocorticoids. 43,48,83,111 High doses of glucocorticoids have been shown to stimulate transcription of ENaC in several sodium transporting epithelia as well as in the lung.…”