Expression of eNOS in the lungs of neonates with pulmonary hypertension

• Published in: Experimental and molecular pathology 2011-02, Vol.90 (1), p.9-12
• Main Authors: Sood, Beena G., Wykes, Susan, Landa, Marina, De Jesus, Lilia, Rabah, Raja
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Case-Control Studies; Congenital diaphragmatic hernia; Endothelial nitric oxide synthase; Endothelium, Vascular - enzymology; Endothelium, Vascular - pathology; Female; Hernia, Diaphragmatic - complications; Hernia, Diaphragmatic - enzymology; Hernia, Diaphragmatic - pathology; Hernias, Diaphragmatic, Congenital; Humans; Hypertension, Pulmonary - enzymology; Hypertension, Pulmonary - etiology; Hypertension, Pulmonary - pathology; Immunohistochemistry; Infant, Newborn; Investigative techniques, diagnostic techniques (general aspects); Lung - blood supply; Lung - metabolism; Lung - pathology; Male; Medical sciences; Neonate; Nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Synthase Type III - metabolism; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Persistent Fetal Circulation Syndrome - complications; Persistent Fetal Circulation Syndrome - enzymology; Persistent Fetal Circulation Syndrome - pathology; Persistent pulmonary hypertension of the newborn; Pneumology; Pulmonary hypertension. Acute cor pulmonale. Pulmonary embolism. Pulmonary vascular diseases; Retrospective Studies; Up-Regulation
• ISSN: 0014-4800; 1096-0945
• DOI: 10.1016/j.yexmp.2010.11.003

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. To compare the expression of eNOS using IHC in postmortem lung tissue from newborns diagnosed clinically with PPHN and CDH. 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. 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. 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. ► We evaluated pulmonary expression of eNOS in neonatal pulmonary hypertension. ► eNOS was upregulated in postmortem lung tissue in neonatal pulmonary hypertension. ► These results may help understand disease patho-physiology and response to treatment.