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This Article Full Text Full Text (PDF) All Versions of this Article: 290/3/L478    most recent 00124.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Folkesson, H. G. Articles by Kitterman, J. A. Search for Related Content PubMed PubMed Citation Articles by Folkesson, H. G. Articles by Kitterman, J. A.

Congenital diaphragmatic hernia prevents absorption of distal air space fluid in late-gestation rat fetuses

¹Department of Physiology and Pharmacology, Northeastern Ohio Universities College of Medicine, Rootstown, Ohio; and ²Cardiovascular Research Institute and ³Department of Pediatrics, University of California, San Francisco, California

Submitted 21 March 2005 ; accepted in final form 4 October 2005

We hypothesized that congenital diaphragmatic hernia (CDH) may decrease distal air space fluid absorption due to immaturity of alveolar epithelial cells from a loss of the normal epithelial Na⁺ transport, as assessed by amiloride and epithelial Na⁺ channel (ENaC) and Na-K-ATPase expression, as well as failure to respond to endogenous epinephrine as assessed by propranolol. Timed-pregnant dams were gavage fed 100 mg of nitrofen at 9.5-day gestation to induce CDH in the fetuses, and distal air space fluid absorption experiments were carried out on 22-day gestation (term) fetuses. Controls were nitrofen-exposed fetuses without CDH. Absorption of distal air space fluid was measured from the increase in ¹³¹I-albumin concentration in an isosmolar, physiological solution instilled into the developing lungs. In controls, distal air space fluid absorption was rapid and mediated by -adrenoceptors as demonstrated by reversal to fluid secretion after propranolol. Normal lung fluid absorption was also partially inhibited by amiloride. In contrast, CDH fetuses continued to show lung fluid secretion, and this secretion was not affected by either propranolol or amiloride. CDH lungs showed a 67% reduction in -ENaC and -ENaC expression, but no change in ₁-Na-K-ATPase expression. These studies demonstrate: 1) CDH delays lung maturation with impaired distal air space fluid absorption secondary to inadequate Na⁺ uptake by the distal lung epithelium that results in fluid-filled lungs at birth with reduced capacity to establish postnatal breathing, and 2) the main stimulus to lung fluid absorption in near-term control fetuses, elevated endogenous epinephrine levels, is not functional in CDH fetuses.

amiloride sensitivity; distal air space epithelium; epinephrine; Na⁺ transport; pulmonary edema; neonatal respiratory distress syndrome

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