Defective lung vascular development and fatal respiratory distress in endothelial NO synthase-deficient mice: a model of alveolar capillary dysplasia?
Circ Res
; 94(8): 1115-23, 2004 Apr 30.
Article
em En
| MEDLINE
| ID: mdl-15016731
ABSTRACT
Endothelium-derived NO plays a critical role in the regulation of cardiovascular function and structure, as well as acting as a downstream mediator of the angiogenic response to numerous vascular growth factors. Although endothelial NO synthase (eNOS)-deficient mice are viable, minor congenital cardiac abnormalities have been reported and homozygous offspring exhibit high neonatal mortality out of proportion to the severity of these defects. The aim of the present report was to determine whether abnormalities of the pulmonary vascular development could contribute to high neonatal loss in eNOS-deficient animals. We now report that eNOS-deficient mice display major defects in lung morphogenesis, resulting in respiratory distress and death within the first hours of life in the majority of animals. Histological and molecular examination of preterm and newborn mutant lungs demonstrated marked thickening of saccular septae, with evidence of reduced surfactant material. Lungs of eNOS-deficient mice also exhibited a striking paucity of distal arteriolar branches and extensive regions of capillary hypoperfusion, together with misalignment of pulmonary veins, which represent the characteristic features of alveolar capillary dysplasia. We conclude that eNOS plays a previously unrecognized role in lung development, which may have relevance for clinical syndromes of neonatal respiratory distress.
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Base de dados:
MEDLINE
Assunto principal:
Alvéolos Pulmonares
/
Síndrome do Desconforto Respiratório do Recém-Nascido
/
Óxido Nítrico Sintase
/
Pulmão
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Circ Res
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Canadá