The influence of mode of delivery, hormonal status and postnatal O2 environment on epithelial sodium channel (ENaC) expression in perinatal guinea-pig lung.

We have studied factors that potentially modulate the expression of mRNA coding for subunits of the amiloride-sensitive sodium channel, alphaENaC and betaENaC, in lungs of vaginally and Caesarean (CS)-delivered late gestation fetal guinea-pigs. Expression of alphaENaC and betaENaC mRNAs was developmentally regulated in the late gestation fetus, reaching peak levels at term (68 days post conception, PC) and postnatally, respectively. In animals delivered by CS at 65 days PC and term, alphaENaC mRNA expression was significantly increased by day 1 post partum, reaching levels greater than those normally achieved in vaginally delivered animals at term. In contrast, betaENaC mRNA levels remained significantly lower postnatally in animals delivered by CS at 65 days PC compared with those in vaginally and CS-delivered animals at term. Plasma cortisol and total triiodothyronine (T3) levels increased towards term, were higher 1 day after vaginal delivery but declined towards pre-term levels by day 3. Cortisol levels also increased rapidly in the CS-delivered animals, reaching levels similar to those in vaginally delivered animals at day 1. Plasma T3 levels at days 1 and 3 were significantly lower in animals delivered by CS at 65 days PC. The increase in alphaENaC mRNA paralleled the increase in plasma cortisol after delivery, but not T3, and inhibition of cortisol synthesis with 2-methyl-1,2-di-3-pyridyl-1-propanone (metyrapone) after CS delivery suppressed the increase in alphaENaC mRNA expression. Concomitant with the increase in alphaENaC mRNA expression after CS delivery at 65 days PC was an increase in the amiloride-blockable component of lung fluid clearance by day 3 postnatally. We conclude that in late gestation guinea-pigs delivered by CS there is a significant increase in lung alphaENaC expression postnatally, which is mediated, in part, by the postnatal rise in cortisol at delivery. This in turn leads to an increase in amiloride-sensitive lung fluid clearance, which is unrelated to labour.