Biology Reference
In-Depth Information
Keywords Bronchopulmonary dysplasia
cAMP
cGMP
Congenital diaphrag-
matic hernia
Nitric oxide
Persistent pulmonary hypertension of the newborn
Phosphodiesterase
Prostacyclin
Abbreviations
BPD Bronchopulmonary dysplasia
CDH Congenital diaphragmatic hernia
COX Cyclooxygenase
eNOS Endothelial nitric oxide synthase
ET-1 Endothelin-1
FPASMC Fetal pulmonary artery smooth muscle cells
H
2
O
2
Hydrogen peroxide
iNOS
Inducible nitric oxide synthase
iNO
Inhaled nitric oxide
MAS
Meconium aspiration syndrome
NAC
N
-acetyl-cysteine
NSAIDs
Nonsteroidal anti-inflammatory drugs
PPHN
Persistent pulmonary hypertension of the newborn
PDE
Phosphodiesterase
PGIS
Prostacyclin synthase
ROS
Reactive oxygen species
RVH
Right ventricular hypertrophy
sGC
Soluble guanylate cyclase
1 Phosphodiesterases in the Pathophysiology of Neonatal
Pulmonary Hypertension
1.1 Normal Pulmonary Vascular Transition
Pulmonary hypertension is normal during fetal life. Because the placenta, not the
lung, serves as the organ of gas exchange, only 10% of the cardiac output is
circulated through the pulmonary vascular bed. In utero, pulmonary pressures are
equivalent to systemic pressures due to elevated pulmonary vascular resistance.
As gestation and fetal lung growth progress, rapid vascular growth increases the
number of small pulmonary arteries within the lung by tenfold, preparing the lungs
to accept the dramatic increase in blood flow that occurs at birth (Levin et al.
1976
).
Despite this increase in vascular surface area, pulmonary vascular resistance actu-
ally increases with gestational age when corrected for lung or body weight. These
findings indicate that vascular constriction must play a key role in maintaining high
pulmonary vascular tone during fetal life. There are multiple pathways involved in
maintaining high pulmonary vascular tone in utero. Some of the known pulmonary
