Expression of eNOS in the lungs of neonates with pulmonary hypertension.
BACKGROUND
Neonatal hypoxemic respiratory failure (NHRF) is usually associated with reversible persistent pulmonary hypertension (PPHN). Congenital diaphragmatic hernia (CDH), a cause of refractory NHRF, is associated with irreversible pulmonary hypertension. Nitric oxide (NO) generated in the pulmonary vascular endothelium by endothelial nitric oxide synthase (eNOS) plays a pivotal role in perinatal circulatory adaptation.


OBJECTIVE
To compare the expression of eNOS using IHC in postmortem lung tissue from newborns diagnosed clinically with PPHN and CDH.


METHODS
Formalin-fixed lung tissue from infants who died following treatment for PPHN (n=12) or CDH (n=8) and age and gender matched controls who died from non-respiratory causes (Control, n=14) was evaluated for expression and staining intensity (1-4 scale) of eNOS using IHC.


RESULTS
Mean gestational and postnatal age was comparable across groups. Histological evidence of chronic lung disease, pulmonary hypoplasia and pulmonary hypertension were seen more frequently in CDH compared to PPHN and control infants. eNOS expression was increased in arteriolar media of PPHN infants compared to Controls (p=0.027). CDH infants had increased intensity of staining for eNOS in the arteriolar endothelium (p=0.022) compared to control and PPHN infants and in the alveolar lining (p=0.002) compared to Controls.


CONCLUSIONS
Upregulation of eNOS was seen both in infants with CDH and PPHN but was more marked in infants with CDH. These findings may have implications for understanding disease pathophysiology in cases with fatal outcome and development of novel therapies for neonatal pulmonary hypertension.
Division of Neonatal-Perinatal Medicine, Children's Hospital of Michigan and Wayne State University, Detroit, MI 48201, USA. bsood@med.wayne.edu
Beena G
BG
Sood
Susan
S
Wykes
Marina
M
Landa
Lilia
L
De Jesus
Raja
R
Rabah
D016022:Case-Control Studies; D004730:Endothelium, Vascular / Q000201:enzymology / Q000473:pathology; D005260:Female; D006548:Hernia, Diaphragmatic / Q000150:complications / Q000201:enzymology / Q000473:pathology; D065630:Hernias, Diaphragmatic, Congenital; D006801:Humans; D006976:Hypertension, Pulmonary / Q000201:enzymology* / Q000209:etiology / Q000473:pathology; D007150:Immunohistochemistry; D007231:Infant, Newborn; D008168:Lung / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D010547:Persistent Fetal Circulation Syndrome / Q000150:complications / Q000201:enzymology / Q000473:pathology; D012189:Retrospective Studies; D015854:Up-Regulation
D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III