ADRENAL HORMONE EFFECTS ON LUNG LIQUID PRODUCTION IN FETAL SHEEP.▴ 358

Abstract

Aldosterone is a mineralocorticoid hormone that increases Na,K-ATPase activity in both airway and distal lung epithelium of fetal sheep (Kullama et al, FASEB J 10: in press, 1996). We previously reported (Kullama et al, FASEB J 9:A568, 1995) that intravenous infusion of aldosterone for 24 h increased net production of lung liquid (Jv) in immature fetal sheep (125 d gestation; term = 147 d), but decreased Jv in more mature fetal sheep (≥136 d gestation). These different effects of aldosterone on Jv at different stages of development may reflect maturational changes in the respiratory tract epithelium, which is predominantly a Cl- secreting membrane early in gestation, switching to a Na+ absorbing membrane around the time of birth. To see if glucocorticoid treatment might modify the response of the immature lung epithelium to aldosterone, we measured Jv in 5 preterm (125± 1 d gestation) fetal sheep before and at the end of a 24-h iv infusion of aldosterone (5 μg/h), and again at the end of a 24-h simultaneous iv infusion of aldosterone and cortisol (10 mg/24 h). Each fetus had a chronically implanted tracheal loop cannula that enabled us to assess Jv by measuring serial changes in the concentration of an impermeant tracer,125 I-albumin, that was added to lung liquid and well mixed within the lung lumen at the start of each study. Jv (mean ± SD) averaged 11.6± 4.4 ml/h before aldosterone, 14.4 ± 8.5 ml/h after 24 h of iv aldosterone, and 8.7 ± 5.8 ml/h after 24 h of iv aldosterone plus cortisol. This decrease in Jv occurred in all 5 studies. Thus, glucocorticoid administration to immature fetal sheep modifies the respiratory epithelial response to aldosterone, with a resultant decrease in net production of lung luminal liquid. It is therefore possible that birth-related increases in the plasma concentration of adrenal hormones, including aldosterone and cortisol, contribute to the decrease in lung liquid that occurs near birth. (Supported by NIH #HL 49098)