Vol. 277, Issue 4, L709-L718, October 1999
Abnormal lung growth and the development of pulmonary
hypertension in the Fawn-Hooded rat
Timothy D.
le Cras1,
Dug-Ha
Kim2,
Sarah
Gebb3,
Neil E.
Markham1,
John M.
Shannon3,
Rubin M.
Tuder4, and
Steven H.
Abman1
1 Pediatric Heart Lung Center,
Department of Pediatrics, and
4 Department of Pathology,
University of Colorado School of Medicine and The Children's Hospital,
Denver 80262; 3 National
Jewish Hospital, Denver, Colorado 80206; and
2 Department of Pediatrics, Hallym University,
150-030 Seoul, South Korea
The Fawn-Hooded
rat (FHR) strain develops accelerated and severe pulmonary hypertension
when exposed to slight decreases in alveolar
PO2. We recently observed that adult
FHR lungs showed a striking pattern of disrupted alveolarization and
hypothesized that abnormalities in lung growth in the perinatal period
predisposes the FHR to the subsequent development of pulmonary
hypertension. We found a reduction in lung weight in the fetus and
1-day- and 1-wk-old FHR compared with a normal rat strain
(Sprague-Dawley). Alveolarization was reduced in infant and adult FHR
lungs. In situ hybridization showed similar patterns of expression of
two epithelial markers, surfactant protein C and 10-kDa Clara cell secretory protein, suggesting that the FHR lung is not characterized by
global delays in epithelial maturation. Barium-gelatin angiograms demonstrated reduced background arterial filling and density in adult
FHR lungs. Perinatal treatment of FHR with supplemental oxygen
increased alveolarization and reduced the subsequent development of
right ventricular hypertrophy in adult FHR. We conclude that the FHR
strain is characterized by lung hypoplasia with reduced alveolarization
and increased risk for developing pulmonary hypertension. We speculate
that altered oxygen sensing may cause impaired lung alveolar and
vascular growth in the FHR.
alveolarization; lung development; lung hypoplasia; bronchopulmonary dysplasia
