Endothelin Receptor Expression in Human Lungs of Newborns With Congenital Diaphragmatic Hernia

J Pathol. 2005 Jan;205(1):112-8. doi: 10.1002/path.1677.


Congenital diaphragmatic hernia (CDH) is a major cause of refractory respiratory failure in the neonatal period and is characterized by persistent pulmonary hypertension of the newborn (PPHN) and pulmonary hypoplasia. Endothelin-1 (ET-1) dysregulation may play a significant role in the pathophysiology of PPHN and ET-1 acts through binding to type A (ETA) and type B (ETB) receptors. Therefore, ETA and ETB receptor protein expression was studied using immunohistochemistry in 10 lung specimens obtained from newborns with CDH, and 4 normal lung specimens, in order to explore whether dysregulation of ETA and ETB expression contributes to PPHN. ETA and ETB mRNAs were then quantified using real-time RT-PCR in laser-microdissected pulmonary resistive arteries. In the lungs of newborns with CDH, immunohistochemistry of both ETA and ETB receptors demonstrated over-expression in the thickened media of pulmonary arteries. Using laser microdissection and real-time RT-PCR, higher levels of ETA and ETB mRNA were found in CDH pulmonary arteries than in controls: this increase was more pronounced for ETA mRNA. This study provides the first demonstration of ET-1 receptor dysregulation in association with structural alteration of pulmonary arteries in newborns with CDH and PPHN. This dysregulation preferentially affects the ETA receptor. These results suggest that dysregulation of ET-1 receptors may contribute to PPHN associated with CDH.

MeSH terms

  • Body Weight
  • Female
  • Gene Expression
  • Hernia, Diaphragmatic / complications
  • Hernia, Diaphragmatic / metabolism*
  • Hernia, Diaphragmatic / pathology
  • Hernias, Diaphragmatic, Congenital
  • Humans
  • Infant, Newborn
  • Lung / metabolism*
  • Lung / pathology
  • Male
  • Microdissection / methods
  • Organ Size
  • Persistent Fetal Circulation Syndrome / etiology
  • Persistent Fetal Circulation Syndrome / metabolism
  • Persistent Fetal Circulation Syndrome / pathology
  • Pulmonary Artery / metabolism
  • RNA, Messenger / genetics
  • Receptor, Endothelin A / genetics
  • Receptor, Endothelin A / metabolism
  • Receptor, Endothelin B / genetics
  • Receptor, Endothelin B / metabolism
  • Receptors, Endothelin / metabolism*
  • Retrospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction


  • RNA, Messenger
  • Receptor, Endothelin A
  • Receptor, Endothelin B
  • Receptors, Endothelin