SALT AND WATER TRANSPORT ACROSS THE ALVEOLAR EPITHELIUM IN THE DEVELOPING LUNG - CORRELATIONS BETWEEN FUNCTION AND RECENT MOLECULAR-BIOLOGYADVANCES (REVIEW)

Significant progress have been made in understanding the mechanisms of alveolar fluid clearance at the time of birth and the transition from placental oxygenation to air breathing. During fetal life, the mammal ian lung is a fluid filled secretory organ that fills no respiratory f unction. Its potential air spaces are filled with fluid that is active ly secreted in response to an osmotic force generated by Cl--secretion and the fluid-filled lung is necessary for a proper development of th e air-breathing lung. As term approaches, net Cl--secretion decreases, which is accompanied by a decreased secretion rate of the fluid into the air spaces. Concomitantly with the decreased Cl--secretion, the al veolar epithelium begins to absorb Na+ to prepare for fluid absorption and the air breathing life. The causes for the decreased Cl--secretio n and the beginning of the Na+ absorption are not clear. Alterations i n the hormonal milieu of the lung as well as changes in plasma stress hormone levels have been suggested to play roles. The switch from a pl acental oxygenation to pulmonary oxygenation requires that the fluid i n the air spaces be rapidly removed from the lung lumen. Recent studie s have demonstrated that removal of the alveolar fluid at birth is reg ulated via endogenous plasma epinephrine in the newborn. Molecular, ce llular, and whole animal in vivo studies have demonstrated that fluid absorption at birth is related to expression and function of the epith elial sodium channel (ENaC). Several different in vivo and in vitro pr eparations have been used to investigate the mechanisms of alveolar fl uid transport, primarily in adult lungs and have demonstrated that alv eolar fluid absorption is driven by active Na+ transport. Both catecho lamine-dependent and -independent regulatory mechanisms have been iden tified, probably acting on ENaC and other apical sodium channels and/o r the basolaterally located Na+,K+-ATPase. Future studies are needed t o integrate new insights to the molecular mechanisms behind fluid clea rance with their function in both normal and pathological lungs.