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stimulates alveolar fluid absorption in fetal guinea pig lungs via the hypothalamus-pituitary-adrenal gland axis
Department of Physiology and Pharmacology, Northeastern Ohio Universities College of Medicine, Rootstown, Ohio 44272-0095
Submitted 3 July 2003 ; accepted in final form 23 November 2003
We tested the hypothesis that interleukin (IL)-1
-induced cortisol synthesis stimulates alveolar fluid clearance in preterm fetuses. IL-1
was administered subcutaneously daily to timed-pregnant guinea pigs for 3 days with and without simultaneous cortisol synthesis inhibition by metyrapone. Fetuses were obtained by abdominal hysterotomy at 61 and 68 days gestation and instilled with isosmolar 5% albumin in the lungs, and alveolar fluid movement was measured over 1 h from the change in alveolar protein concentration. Alveolar fluid clearance was induced at 61 days gestation and stimulated at 68 days gestation by IL-1
, which both were attenuated by cortisol synthesis inhibition. Plasma ACTH and cortisol concentrations were increased by IL-1
at both gestational ages, and metyrapone reduced cortisol concentrations. IL-1
was mostly low or undetectable in both fetal and maternal blood. Prenatal alveolar fluid clearance, when present as well as IL-1
induced, was always propranolol and amiloride sensitive, suggesting that
-adrenoceptor stimulation and amiloride-sensitive Na+ channels were critical for fluid absorption. IL-1
increased lung
-adrenoceptor density at gestation day 61, and cortisol synthesis inhibition attenuated the increased
-adrenoceptor density. Epithelial Na+ channel and Na+-K+-ATPase subunit expressions were both increased by IL-1
and attenuated by cortisol synthesis inhibition. These results may explain why babies delivered preterm after intrauterine inflammation have a reduced risk of developing severe respiratory distress.
adrenocorticotropic hormone; alveolar epithelium;
-adrenoceptors; cortisol; epithelial sodium channel; epinephrine; interleukin-1
; respiratory distress syndrome; prenatal lung development; sodium transport
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