Nitric oxide synthases in infants and children with pulmonary hypertension and congenital heart disease.
BACKGROUND
Nitric oxide is an important regulator of vascular tone in the pulmonary circulation. Surgical correction of congenital heart disease limits pulmonary hypertension to a brief period.


OBJECTIVE
The study has measured expression of endothelial (eNOS), inducible (iNOS), and neuronal nitric oxide synthase (nNOS) in the lungs from biopsies of infants with pulmonary hypertension secondary to cardiac abnormalities (n = 26), compared to a control group who did not have pulmonary or cardiac disease (n = 8).


METHODS
eNOS, iNOS and nNOS were identified by immunohistochemistry and quantified in specific cell types.


RESULTS
Significant increases of eNOS and iNOS staining were found in pulmonary vascular endothelial cells of patients with congenital heart disease compared to control infants. These changes were confined to endothelial cells and not present in other cell types. Patients who strongly expressed eNOS also had strong expression of iNOS.


CONCLUSIONS
Upregulation of eNOS and iNOS occurs at an early stage of pulmonary hypertension, and may be a compensatory mechanism limiting the rise in pulmonary artery pressure.
Hoehn
Thomas
T
Neonatology and Pediatric Intensive Care Medicine, Department of General Pediatrics, Heinrich-Heine-University, Duesseldorf, Germany. thomas.hoehn@uni-duesseldorf.de
Stiller
Brigitte
B
McPhaden
Allan R
AR
Wadsworth
Roger M
RM
D001706:Biopsy; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D042783:Endothelial Cells / Q000201:enzymology*; D005260:Female; D006330:Heart Defects, Congenital / Q000150:complications / Q000201:enzymology*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000201:enzymology* / Q000209:etiology; D007150:Immunohistochemistry; D007223:Infant; D008168:Lung / Q000098:blood supply*; D008297:Male; D052248:Nitric Oxide Synthase Type I / Q000032:analysis; D052247:Nitric Oxide Synthase Type II / Q000032:analysis*; D052250:Nitric Oxide Synthase Type III / Q000032:analysis*; D015854:Up-Regulation
C496320:NOS1 protein, human; C496319:NOS2 protein, human; C496314:NOS3 protein, human; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III