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Pediatric Surgery International

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01-01-2010 | Original Article

Upregulation of Endothelin Receptors A and B in the nitrofen induced hypoplastic lung occurs early in gestation

Authors: Jens Dingemann, Takashi Doi, Elke Ruttenstock, Prem Puri

Published in: Pediatric Surgery International | Issue 1/2010

Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusion

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.

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Title: Upregulation of Endothelin Receptors A and B in the nitrofen induced hypoplastic lung occurs early in gestation
Authors: Jens Dingemann
Takashi Doi
Elke Ruttenstock
Prem Puri
Publication date: 01-01-2010
Publisher: Springer-Verlag
Published in: Pediatric Surgery International / Issue 1/2010
Print ISSN: 0179-0358
Electronic ISSN: 1437-9813
DOI: https://doi.org/10.1007/s00383-009-2514-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Upregulation of Endothelin Receptors A and B in the nitrofen induced hypoplastic lung occurs early in gestation

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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