Neonatal dexamethasone treatment increases the risk for pulmonary hypertension in adult rats
1 Pediatric Heart Lung Center, Department of Pediatrics, 2 Cardiovascular Pulmonary Research Laboratory, Department of Medicine, and 3 Department of Radiological Sciences, University of Colorado School of Medicine, Denver, Colorado 80262 Dexamethasone (Dex) treatment during a critical period of l...
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Published in | American journal of physiology. Lung cellular and molecular physiology Vol. 278; no. 4; pp. 822 - L829 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
01.04.2000
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Subjects | |
Online Access | Get full text |
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Summary: | 1 Pediatric Heart Lung Center, Department of
Pediatrics, 2 Cardiovascular
Pulmonary Research Laboratory, Department of Medicine, and
3 Department of Radiological Sciences, University
of Colorado School of Medicine, Denver, Colorado 80262
Dexamethasone (Dex) treatment during a critical period of
lung development causes lung hypoplasia in infant rats. However, the
effects of Dex on the pulmonary circulation are unknown. To determine
whether Dex increases the risk for development of pulmonary hypertension, we treated newborn Sprague-Dawley rats with Dex (0.25 µg/day, days 3 - 13 ). Litters were divided equally
between Dex-treated and vehicle control (ethanol) rats. Rats were
raised in either room air until 10 wk of age (normoxic groups) or room air until 7 wk of age and then in a hypoxia chamber (inspired O 2 fraction = 0.10; hypoxic groups) for 3 wk to induce
pulmonary hypertension. Compared with vehicle control rats, Dex
treatment of neonatal rats reduced alveolarization (by 42%; P < 0.05) and barium-filled pulmonary artery counts (by 37%; P < 0.05) in 10-wk-old adults. Pulmonary arterial pressure and the
ratio of right ventricle to left ventricle plus septum weights
(RV/LV+S) were higher in 10-wk-old Dex-treated normoxic rats compared
with those in normoxic control rats (by 16 and 16% respectively;
P < 0.05). Small pulmonary arteries of adult normoxic
Dex-treated rats showed increased vessel wall thickness compared with
that in control rats (by 15%; P < 0.05). After 3 wk of
hypoxia, RV/LV+S values were 36% higher in rats treated with Dex in
the neonatal period compared with those in hypoxic control rats
( P < 0.05). RV/LV+S was 42% higher in hypoxic control rats
compared with those in normoxic control rats ( P < 0.05). We
conclude that Dex treatment of neonatal rats caused sustained lung
hypoplasia and increased pulmonary arterial pressures and augmented the
severity of hypoxia-induced pulmonary hypertension in adult rats.
lung development; glucocorticoids; alveolarization; congenital
diaphragmatic hernia; bronchopulmonary dysplasia; hypoxia |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1040-0605 1522-1504 |
DOI: | 10.1152/ajplung.2000.278.4.L822 |