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This Article Full Text Full Text (PDF) All Versions of this Article: 291/1/L119    most recent 00395.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (12) Citing Articles via Google Scholar Google Scholar Articles by Balasubramaniam, V. Articles by Abman, S. H. Search for Related Content PubMed PubMed Citation Articles by Balasubramaniam, V. Articles by Abman, S. H.

Inhaled NO restores lung structure in eNOS-deficient mice recovering from neonatal hypoxia

Pediatric Heart Lung Center, Department of Pediatrics, University of Colorado School of Medicine, Denver, Colorado

Submitted 23 August 2005 ; accepted in final form 25 January 2006

We have previously shown that neonatal mice deficient in endothelial nitric oxide synthase (eNOS^–/–) are more susceptible to hypoxic inhibition of alveolar and vascular growth. Although eNOS is downregulated, the role of nitric oxide (NO) during recovery after neonatal lung injury is poorly understood. We hypothesized that lung vascular and alveolar growth would remain impaired in eNOS^–/– mice during recovery in room air and that NO therapy would augment compensatory lung growth in the eNOS^–/– mice during recovery. Mice (1 day old) from heterozygous (eNOS^+/–) parents were placed in hypobaric hypoxia (FI_O2= 0.16). After 10 days, pups were to recovered in room air (HR group) or inhaled NO (10 parts/million; HiNO group) until 3 wk of age, when lung tissue was collected. Morphometric analysis revealed that the eNOS^–/– mice in the HR group had persistently abnormal lung structure compared with eNOS-sufficient (eNOS^+/+) mice (increased mean linear intercept and reduced radial alveolar counts, nodal point density, and vessel density). Lung morphology of the eNOS^+/– was not different from eNOS^+/+. Inhaled NO after neonatal hypoxia stimulated compensatory lung growth in eNOS^–/– mice that completely restored normal lung structure. eNOS^+/– mice (HR group) had a 2.5-fold increase in lung vascular endothelial growth factor (VEGFR)-2 protein compared with eNOS^+/+ (P < 0.05). eNOS^–/– mice (HiNO group) had a 66% increase in lung VEGFR-2 protein compared with eNOS^–/– (HR group; P < 0.01). We conclude that deficiency of eNOS leads to a persistent failure of lung growth during recovery from neonatal hypoxia and that, after hypoxia, inhaled NO stimulates alveolar and vascular growth in eNOS^–/– mice.

nitric oxide; endothelial nitric oxide

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