ABSTRAa. Previous studies have shown that i.v. arginine vasopressin (AVP) decreases but does not stop lung fluid secretion in term fetuses not in labor. Although it has been presumed that the response to AVP results from augmented sodium transport, there is controversy whether AVP actually does affect sodium transport in mammalian lung epithelium. To determine if AVP or aldosterone could alone or together augment sodium transport in the perinatal lung, we studied primary cultures of fetal rat distal lung epithelium in Ussing chambers. The short circuit current of these sodium-transporting cells was not affected by the application of either 30 or 300 mU/mL AVP whether or not they were previously exposed to aldosterone M). Aldosterone also did not affect the baseline bioelectric properties. Short circuit current increased in response to 8-bromo cAMP M) and 3-isobutyl-1-methylxanthine M) to levels 169 f 16 (SEM) and 172 f 7% of respective baseline values. AVP had no effect in cells pretreated with 3-isobutyl-1-methylxanthine. Monolayers also did not respond to atrial natriuretic peptide (lo-" to lo-' M). Monolayers of Na-absorbing A6 renal epithelium did increase short circuit current with either aldosterone or AVP. AVP increased endogenous cAMP levels in A6 but not fetal rat distal lung epithelium cells, suggesting that fetal rat distal lung epithelium lacks V2 receptors. These studies demonstrate that AVP does not increase ion ' transport in cultured fetal distal lung epithelium although these cells possess the necessary second messenger system. (Pediatr Res 31: 318-322,1992) Abbreviations AVP, arginine vasopressin FLE, fetal rat distal lung epithelium Isc, short circuit current IBMX, isobutyl-1-methylxanthine 8 Br, bromoadenosine HBSS, Hanks' balanced salt solution PD, potential difference R, resistance ANP, atrial natriuretic peptide MEM, minimum essential medium At birth, the newborn lung is filled with fluid, which must be cleared before efficient gas exchange can take place. Epithelial have demonstrated that the sodium transport blocker amiloride can block p-agonist-induced fluid absorption in the fetal lamb lung ( 1 ) and delay fluid clearance in newborn guinea piglets (2). Studies using amiloride analogs have also suggested that the ability of amiloride to delay postnatal lung water clearance results from its blockade of epithelial sodium channels (3). To investigate mechanisms that could increase this perinatal lung epithelial sodium transport, we chose to study AVP because it reduces fluid secretion in fetal goats ( 4 ) and lambs ( 5 ) and circulates in the fetus in increased concentrations during normal delivery (6).Numerous studies (e.g. Refs. 7-1 1 ) have demonstrated that AVP can increase sodium transport in some non-lung tissues by increasing the number of active membrane-associated sodium channels (10). It is unknown whether these observations can be extrapolated to different species or to different epithelial membranes. For example, it has been reported that the AVP increases sodium transport i...