Dose-dependent effects of glucocorticoids on pulmonary vascular development in a murine model of hyperoxic lung injury

Autor: Kathryn N. Farrow, Marta Perez, Herminio J. Cardona, Keng Jin Lee, Joann M. Taylor, Kamila Wisniewska
Rok vydání: 2016
Předmět:
medicine.medical_specialty
Pathology
Hydrocortisone
Hypertension
Pulmonary
Hyperoxia
Pulmonary Artery
030204 cardiovascular system & hematology
Lung injury
Article
Muscle hypertrophy
Mice
03 medical and health sciences
0302 clinical medicine
Right ventricular hypertrophy
030225 pediatrics
medicine.artery
Internal medicine
medicine
Animals
Humans
Glucocorticoids
Lung
Cyclic Nucleotide Phosphodiesterases
Type 5
Dose-Response Relationship
Drug
Hypertrophy
Right Ventricular
business.industry
Lung Injury
respiratory system
medicine.disease
Pulmonary hypertension
Elastin
respiratory tract diseases
3. Good health
Mice
Inbred C57BL
Pulmonary Alveoli
Endocrinology
medicine.anatomical_structure
cGMP-specific phosphodiesterase type 5
Pediatrics
Perinatology and Child Health
Pulmonary artery
medicine.symptom
business
Signal Transduction
Zdroj: Pediatric research
ISSN: 1530-0447
0031-3998
DOI: 10.1038/pr.2016.1
Popis: BACKGROUND Exposure of neonatal mice to hyperoxia results in pulmonary vascular remodeling and aberrant phosphodiesterase-5 (PDE5) signaling. Although glucocorticoids are frequently utilized in the NICU, little is known about their effects on the developing pulmonary vasculature and on PDE5. We sought to determine the effects of hydrocortisone (HC) on pulmonary vascular development and on PDE5 in a neonatal mouse model of hyperoxic lung injury. METHODS C57BL/6 mice were placed in 21% O2 or 75% O2 within 24h of birth and received HC (1, 5, or 10 mg/kg subcutaneously every other day) or vehicle. At 14d, right ventricular hypertrophy (RVH), medial wall thickness (MWT), lung morphometry, and pulmonary artery (PA) PDE5 activity were assessed. PDE5 activity was measured in isolated pulmonary artery smooth muscle cells (PASMC) exposed to 21% or 95% O2 ± 100nM HC for 24h. RESULTS Hyperoxia resulted in alveolar simplification, RVH, increased MWT, and increased PA PDE5 activity. HC decreased hyperoxia-induced RVH and attenuated MWT. HC had dose-dependent effects on alveolar simplification. HC decreased hyperoxia-induced PDE5 activity in vivo and in vitro. CONCLUSIONS HC decreases hyperoxia-induced pulmonary vascular remodeling and attenuates PDE5 activity. These findings suggest that HC may protect against hyperoxic injury in the developing pulmonary vasculature.
Databáze: OpenAIRE
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