Journal
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
Volume 279, Issue 2, Pages L283-L291Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajplung.2000.279.2.L283
Keywords
alveolarization; lung development; lung hypoplasia; endothelial nitric oxide synthase
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Funding
- NHLBI NIH HHS [HL-57144] Funding Source: Medline
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The Fawn-Hooded rat (FHR) is a genetic strain that has been extensively studied as a model of primary pulmonary hypertension in adult rats. Based on our recent observations that alveolar number and pulmonary arterial density are reduced in FHRs raised at Denver's altitude, we hypothesized that early abnormalities in pulmonary vascular development contribute to the progression of pulmonary hypertension in the FHR. We found that endothelial nitric oxide synthase (eNOS) protein content was lower in the lungs of fetal, 1- and 7-day-old, 3-week-old, and adult FHRs compared with that in the normal Sprague-Dawley (SDR) and Fischer rat strains, all raised at Denver's altitude. In contrast, lung expression of the endothelial proteins kinase insert domain-containing receptor/fetal liver kinase-1 (KDR/Flk-1) and platelet endothelial cell adhesion molecule-1 (CD31) was not different between strains. Barium arteriograms showed that pulmonary arterial density was reduced in 3-week-old FHRs compared with SDRs. Perinatal treatment of FHRs with mild hyperbaria to simulate sealevel alveolar PO2 improved lung eNOS content and pulmonary vascular growth and reduced right ventricular hypertrophy. We conclude that the development of pulmonary hypertension in Denver-raised FHRs is characterized by reductions in lung eNOS expression and abnormal pulmonary vascular growth during the fetal, neonatal, and postnatal periods.
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