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Dingemann, J; Doi, T; Ruttenstock, E; Puri, P.
Upregulation of endothelin receptors A and B in the nitrofen induced hypoplastic lung occurs early in gestation.
Pediatr Surg Int. 2010; 26(1): 65-69. Doi: 10.1007/s00383-009-2514-8
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Co-authors Med Uni Graz
Ruttenstock Elke Maria
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Abstract:
Pulmonary hypoplasia and persistent pulmonary hypertension (PPH) aggravate clinical courses in congenital diaphragmatic hernia (CDH). Endothelin 1 enhances PPH by vasoconstriction and proliferation of vessel walls. Up-regulation of pulmonary Endothelin Receptors A and B (EDNRA, EDNRB) has been reported in human CDH and animal models, but the onset of those alterations during lung development remains unclear. We hypothesized that pulmonary expression of EDNRA and EDNRB is up-regulated at early gestational stages in the nitrofen model. Pregnant rats were exposed to nitrofen or vehicle on gestational day 9 (D9). Embryos were sacrificed on D15, D18 and D21 and divided into nitrofen- and control group. Pulmonary RNA was extracted and mRNA levels of EDNRA and EDNRB were determined by real-time PCR. Immunohistochemistry for protein expression of both receptors was performed. mRNA levels of EDNRA and EDNRB were significantly increased in the nitrofen group on D15, D18 and D21. Immunohistochemistry revealed increased pulmonary vascular expression of EDNRA and EDNRB compared to controls. Altered expression of EDNRA and EDNRB is an early event in lung morphogenesis in the nitrofen model. We speculate that pulmonary arteries in CDH become excessively muscularised in early fetal life, becoming unable to adapt normally at birth.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Disease Models, Animal -
Female -
Gestational Age -
Hernia, Diaphragmatic - congenital Hernia, Diaphragmatic - embryology Hernia, Diaphragmatic - genetics
Immunohistochemistry -
Lung - drug effects Lung - embryology Lung - metabolism
Lung Diseases - chemically induced Lung Diseases - complications Lung Diseases - genetics
Phenyl Ethers - toxicity
Polymerase Chain Reaction -
Pregnancy -
RNA, Messenger - biosynthesis RNA, Messenger - genetics
Rats -
Rats, Sprague-Dawley -
Receptor, Endothelin A - biosynthesis Receptor, Endothelin A - genetics
Receptor, Endothelin B - biosynthesis Receptor, Endothelin B - genetics
Up-Regulation -

Find related publications in this database (Keywords)
Congenital diaphragmatic hernia
Nitrofen
Persistent pulmonary hypertension
Endothelin
Endothelin Receptor A
Endothelin Receptor B
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