Honeymoon Period in Newborn Rats With CDH Is Associated With Changes in the VEGF Signaling Pathway

Karina Miura da Costa, Alexandre Todorovic Fabro, Christiane Becari, Rebeca Lopes Figueira, Augusto F. Schmidt, Rodrigo Ruano, Lourenço Sbragia

Research output: Contribution to journalArticlepeer-review


Background: Patients with congenital diaphragmatic hernia (CDH) have a short postnatal period of ventilatory stability called the honeymoon period, after which changes in pulmonary vascular reactivity result in pulmonary hypertension. However, the mechanisms involved are still unknown. The aim of this study was to evaluate mechanical ventilation's effect in the honeymoon period on VEGF, VEGFR-1/2 and eNOS expression on experimental CDH in rats. Materials and Methods: Neonates whose mothers were not exposed to nitrofen formed the control groups (C) and neonates with left-sided defects formed the CDH groups (CDH). Both were subdivided into non-ventilated and ventilated for 30, 60, and 90 min (n = 7 each). The left lungs (n = 4) were evaluated by immunohistochemistry of the pulmonary vasculature (media wall thickness), VEGF, VEGFR-1/2 and eNOS. Western blotting (n = 3) was performed to quantify the expression of VEGF, VEGFR-1/2 and eNOS. Results: CDH had lower biometric parameters than C. Regarding the pulmonary vasculature, C showed a reduction in media wall thickness with ventilation, while CDH presented reduction with 30 min and an increase with the progression of the ventilatory time (honeymoon period). CDH and C groups showed different patterns of VEGF, VEGFR-1/2 and eNOS expressions. The receptors and eNOS findings were significant by immunohistochemistry but not by western blotting, while VEGF was significant by western blotting but not by immunohistochemistry. Conclusion: VEGF, its receptors and eNOS were altered in CDH after mechanical ventilation. These results suggest that the VEGF-NO pathway plays an important role in the honeymoon period of experimental CDH.

Original languageEnglish (US)
Article number698217
JournalFrontiers in Pediatrics
StatePublished - Jul 16 2021


  • VEGF
  • VEGFR-1
  • VEGFR-2
  • congenital diaphragmatic hernia
  • eNOS enzyme
  • ventilation

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health


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