Abnormal lung growth and the development of pulmonary hypertension in the Fawn-Hooded rat.
The Fawn-Hooded rat (FHR) strain develops accelerated and severe pulmonary hypertension when exposed to slight decreases in alveolar PO(2). 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.
Le Cras
T D
TD
Pediatric Heart Lung Center, Department of Pediatrics, Denver, Colorado 80206, USA. Timothy.Lecras@uchsc.edu
Kim
D H
DH
Gebb
S
S
Markham
N E
NE
Shannon
J M
JM
Tuder
R M
RM
Abman
S H
SH
D000375:Aging / Q000502:physiology; D000792:Angiography; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005333:Fetus / Q000502:physiology; D006976:Hypertension, Pulmonary / Q000235:genetics*; D017380:Hypertrophy, Right Ventricular / Q000517:prevention & control; D008168:Lung / Q000002:abnormalities* / Q000187:drug effects / Q000196:embryology / Q000254:growth & development / Q000473:pathology; D010100:Oxygen / Q000627:therapeutic use; D011295:Prenatal Care; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000196:embryology; D011652:Pulmonary Circulation; D051381:Rats; D011919:Rats, Inbred Strains / Q000235:genetics; D017207:Rats, Sprague-Dawley; D012016:Reference Values
D010100:Oxygen