Sildenafil stimulates and dexamethasone inhibits pulmonary vascular development in congenital diaphragmatic hernia rat lungs
Related Experiment Video
Updated: Apr 30, 2026
The Left Pneumonectomy Combined with Monocrotaline or Sugen as a Model of Pulmonary Hypertension in Rats
Published on: March 8, 2019
Javier Kattan1, Carlos Céspedes, Alvaro González
1Division of Neonatology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
Insights
Phosphodiesterase-5 (PDE-5) inhibitors may improve pulmonary arteriolar development in congenital diaphragmatic hernia (CDH) fetuses. Prenatal corticosteroids, however, may negatively impact arteriolar and arterial development in CDH lungs.
Area of Science:
- Neonatal research
- Developmental biology
- Pharmacology
Background:
- Disrupted pulmonary vascular development, leading to pulmonary hypertension, predicts neonatal mortality in congenital diaphragmatic hernia (CDH) infants.
- Pulmonary hypertension is a critical complication in CDH, impacting infant survival rates.
Purpose of the Study:
- To investigate the effects of prenatal corticosteroids and phosphodiesterase-5 (PDE-5) inhibitors on pulmonary vascular development in CDH.
- To assess potential therapeutic strategies for improving lung development in CDH models.
Main Methods:
- Congenital diaphragmatic hernia (CDH) was induced in fetal rats using nitrofen.
- Fetuses were exposed to either dexamethasone (DEX) or sildenafil (SILD) with L-arginine, alongside a placebo group.
- Lung tissue analysis focused on arteriole and artery counts and medial wall thickness (%MWT).
Main Results:
- Sildenafil (SILD) treatment significantly increased the number of pulmonary arterioles but not arteries.
- Dexamethasone (DEX) treatment resulted in significant decreases in both arteriole and artery counts.
- Neither treatment altered the arteriolar percent medial wall thickness (%MWT) in this model.
Conclusions:
- Phosphodiesterase-5 (PDE-5) inhibitors show promise for enhancing pulmonary arteriolar development in CDH.
- Prenatal corticosteroid exposure may adversely affect pulmonary vascular development in CDH.
- Further research is warranted to explore PDE-5 inhibitors as a therapeutic option for CDH.
Background:
A predictor of neonatal mortality in infants with congenital diaphragmatic hernia (CDH) is disrupted pulmonary vascular development, clinically expressed as pulmonary hypertension.
Objective:
To determine if prenatal corticosteroids and phosphodiesterase-5 (PDE-5) inhibitors have a beneficial effect on pulmonary vascular development in CDH lungs.
Methods:
We induced CDH in fetal rats by giving nitrofen. We then exposed them to dexamethasone or to sildenafil. We separated them into three groups: (1) DEX, 4 pregnant rats received dexamethasone at days E16, E18 and E20; (2) SILD, 4 pregnant rats received sildenafil and L-arginine between E14 and E22, and (3) placebo. We then analyzed the lung of each fetus with CDH at E22. We examined the number of arterioles and arteries, and their percent of medial wall thickness (%MWT).
Results:
We obtained 30 CDH-positive fetuses. We analyzed 3,560 arterioles and 211 arteries. SILD showed a significant increase in the number of arterioles, but no significant increase in the number of arteries. No change was noted in the arteriolar %MWT. In contrast, DEX showed significant decreases in the number of arterioles and arteries and a significant increase in %MWT.
Conclusions:
PDE-5 inhibitors may improve pulmonary arteriolar development in fetuses with CDH. In contrast, prenatal corticosteroids could have deleterious effects on arteriolar and arterial development in CDH lungs.
