Arginine Vasopressin and Atrial Natriuretic Peptide Do Not Alter Ion Transport by Cultured Fetal Distal Lung Epithelium

Abstract

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...

Vasopressin Effects on Lung Liquid Volume in Fetal Sheep

“…This proposed mechanism is consistent with the observation by Goodman et al (38) that AVP increased dome formation in confluent monolayers of cultured lung epithelial cells from adult rats. Contrary to this view, however, three other groups of investigators found no effect of AVP on the bioelectric properties of respiratory epithelium from fetal and adult rats (14,39) and from mature rabbits (40). These observations support the skepticism expressed in a recent commentary on the possible role of vasopressin in stimulating lung liquid clearance by a sodium-dependent process at birth (41).…”

“…In these studies, the inhibitory dose of AVP was sufficient to yield plasma concentrations of the hormone that were at least 10 times greater than those that have been measured in sheep during normal spontaneous labor and delivery (12,13). Moreover, a recent report showed that AVP had no significant effect on the bioelectric properties of confluent monolayers of cultured lung epithelial cells harvested from late-gestation fetal rats (14). Thus, the importance of vasopressin in regulating lung liquid clearance near birth is uncertain.…”

The Impact of Phorbol Ester on the Regulation of Amiloride-Sensitive Epithelial Sodium Channel in Alveolar Type Ii Epithelial Cells

“…On the other hand, in the lung epithelial cells, although it has been demonstrated that the presence of mineralocorticoid receptors in adult and fetal lungs [32], the impact of aldosterone on ENaC regulation is still controversial. It has been reported that treatment with aldosterone did not affect short-circuit current in alveolar type II cells [33] and did not alter the bioelectric properties in FDLE cells [34]. These results show the possibility of differential regulation of ENaC dependent on the various cell types.…”

Role of natriuretic peptides in ion transport mechanisms

“…It has been reported that natriuretic peptides at 10 Ϫ11 to 10 Ϫ8 M do not alter Na ϩ transport by cultured fetal distal lung epithelium. 89 Influx experiments indicated that ANP, via guanylate cyclase A receptor-produced cGMP, decreased the amiloride-sensitive component of 22 Na ϩ influx with no changes in the ouabain-sensitive 86 Rb ϩ influx in cultured alveolar type II cells. 90 These findings were taken to indicate a preferential extrusion of cGMP on the basolateral membrane and inhibition of amiloride-sensitive Na ϩ channels.…”