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 Pot. We recently observed that adult FHR lungs showed a striking pattern of disrupted alveol arization and hypothesized that abnormalities in lung growth in the perinat al period predisposes the FHR to the subsequent development of pulmonary hy pertension. We found a reduction in lung weight in the fetus and 1-day- and l-wk-old FHR compared with a normal rat strain (Sprague-Dawley). Alveolari zation was reduced in infant and adult FHR lungs. In situ hybridization sho wed similar patterns of expression of two epithelial markers, surfactant pr otein C and 10-kDa Clara cell secretory protein, suggesting that the FHR lu ng is not characterized by global delays in epithelial maturation. Barium-g elatin angiograms demonstrated reduced background arterial filling and dens ity 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 ch aracterized by lung hypoplasia with reduced alveolarization and increased r isk for developing pulmonary hypertension. We speculate that altered oxygen sensing may cause impaired lung alveolar and vascular growth in the FHR.