The influence of mode of delivery, hormonal status and postnatal O-2 environment on epithelial sodium channel (ENaC) expression in perinatal guinea-pig lung

1. We have studied factors that potentially modulate the expression of mRNA coding for subunits of the amiloride-sensitive sodium channel, alpha ENaC and beta ENaC, in lungs of vaginally and Caesarean (CS)-delivered late gest ation fetal guinea-pigs. 2. Expression of alpha ENaC and beta ENaC mRNAs was developmentally regulat ed in the late gestation fetus, reaching peak levels at term (68 days post conception, PC) and postnatally, respectively. In animals delivered by CS a t 65 days PC and term, alpha ENaC mRNA expression was significantly increas ed by day 1 post partum, reaching levels greater than those normally achiev ed in vaginally delivered animals at term. In contrast, beta ENaC mRNA leve ls remained significantly lower postnatally in animals delivered by CS at 6 5 days PC compared with those in vaginally and CS-delivered animals at term . 3. Plasma cortisol and total triiodothyronine (T-3) levels increased toward s term, were higher 1 day after vaginal delivery but declined towards pre-t erm levels by day 3. Cortisol levels also increased rapidly in the CS-deliv ered animals, reaching levels similar to those in vaginally delivered anima ls at day 1. Plasma T-3 levels at days 1 and 3 were significantly lower in animals delivered by CS at 65 days PC. 4. The increase in aENaC mRNA paralleled the increase in plasma cortisol af ter delivery, but not T-3, and inhibition of cortisol synthesis with 2-meth yl-1,2-di-3-pyridyl-1-propanone (metyrapone) after CS delivery suppressed t he increase in alpha ENaC mRNA expression. 5. Concomitant with the increase in alpha ENaC mRNA expression after CS del ivery at 65 days PC was an increase in the amiloride-blockable component of lung fluid clearance by day 3 postnatally. 6. We conclude that in late gestation guinea-pigs delivered by CS there is a significant increase in lung alpha ENaC expression postnatally, which is mediated, in part, by the postnatal rise in cortisol at delivery. This in t urn leads to an increase in amiloride-sensitive lung fluid clearance, which is unrelated to labour.