Alveolar Epithelial Fluid Clearance Is Mediated by Endogenous Catecholamines at Birth in Guinea Pigs

Transition from placental to pulmonary oxygenation at birth depends on a rapid removal of fetal lung fluid from the developing alveoli. Alveolar fluid clearance was examined in ventilated, anesthetized developing guinea pigs of the ages newborn, 2-d-old, 5-d-old, 30-d-old, and 60-d-old (adult). An isosmolar 5 % albumin solution was instilled into the lungs of the guinea pigs; the guinea pigs were then studied for 1 h. Alveolar fluid clearance was measured from the increase in alveolar protein concentration as water was reabsorbed. Newborn guinea pigs had a very high alveolar fluid clearance rate that declined rapidly within the first 5 postnatal days towards adult levels. The high alveolar fluid clearance at birth was apparently mediated by the �-adrenergic system as demonstrated by the elevated plasma epinephrine levels and the increased sensitivity to inhibition by the �-adrenergic antagonist propranolol immediately after birth. Surprisingly, exogenous addition of epinephrine was not able to stimulate alveolar fluid clearance in the newborn lung, but exogenous epinephrine stimulation increased over time to adult levels. The elevated alveolar fluid clearance at birth was associated with a significantly greater amiloride sensitivity in the newborn guinea pig lung. Northern blot analysis of distal lung tissue as well as isolated alveolar epithelial type II cells showed and confirmed higher levels of the �-subunit of the epithelial sodium channel mRNA in the newborn lung that rapidly tapered off toward adult levels. In conclusion, these data demonstrate the importance of the �-adrenergic system and amiloride-sensitive sodium transporting pathways for clearance of fetal lung fluid at birth. (J. Clin. Invest. 1998. 101:972–981.) Key words: alveolar epithelium • development • epinephrine • epithelial sodium channel • sodium transpor