Effects of retinoic acid on airspace development and lung collagen in hyperoxia-exposed newborn rats

• Published in: Pediatric research Vol. 48; no. 4; pp. 434 - 444
• Main Authors: VENESS-MEEHAN, Kathleen A, BOTTONE, Frank G, STILES, Alan D
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01.10.2000
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Biological and medical sciences; Collagen - analysis; Collagen - genetics; Dexamethasone - pharmacology; Dexamethasone - therapeutic use; Emergency and intensive care: neonates and children. Prematurity. Sudden death; Gene Expression - drug effects; Glucocorticoids - pharmacology; Glucocorticoids - therapeutic use; Hyperoxia - mortality; Hyperoxia - physiopathology; Immunohistochemistry; Intensive care medicine; Lung - chemistry; Lung - drug effects; Lung - growth & development; Lung Diseases - prevention & control; Lung Volume Measurements; Medical sciences; Procollagen - genetics; Pulmonary Alveoli - drug effects; Pulmonary Alveoli - growth & development; Rats; Rats, Sprague-Dawley; RNA, Messenger - analysis; Tretinoin - pharmacology; Tretinoin - therapeutic use; Premature; Lung disease; Rat; Respiratory disease; Pathogenesis; Treatment efficiency; Induced hyperoxia; Lung; Rodentia; Postnatal development; Prevention; Newborn diseases; Vertebrata; Mammalia; Newborn animal; Collagen; Bronchus disease; Bronchopulmonary dysplasia; Retinoic acid
• ISSN: 0031-3998; 1530-0447
• DOI: 10.1203/00006450-200010000-00004

Impaired septal formation and decreased alveolarization are often caused by hyperoxic injury to the developing lung and are characteristic features of bronchopulmonary dysplasia. Dexamethasone, frequently administered to infants during oxygen exposure, also inhibits septal formation in the newborn lung. Vitamin A administration reduces the incidence of bronchopulmonary dysplasia in vitamin A-deficient premature infants, and retinoic acid improves alveolarization in newborn rats treated with dexamethasone, indicating that retinoic acid may be useful in preventing hyperoxia-induced impaired septation in bronchopulmonary dysplasia. To investigate whether treatment with retinoic acid during exposure to hyperoxia would improve septal formation, newborn rats exposed to > or =90% O(2) from d 3 of life to d 14 were treated with retinoic acid (d 3-13 of life) and/or dexamethasone (d 4-13 of life). In contrast with the effects of retinoic acid on dexamethasone-induced inhibition of alveolarization, we found that retinoic acid did not improve septal formation or decrease airspace size in animals exposed to hyperoxia alone or to hyperoxia plus dexamethasone. Retinoic acid did, however, increase collagen in airspace walls as demonstrated by staining and immunohistochemistry. There was no increase in procollagen mRNA by Northern hybridization analysis, indicating that retinoic acid-associated increases in lung collagen are likely due to posttranscriptional regulation. There was a trend toward increased survival in hyperoxia in animals treated with retinoic acid to the extent that combined therapy with retinoic acid and dexamethasone resulted in the greatest improvement in animal survival. These results suggest that although retinoic acid may be of benefit in hyperoxia-induced lung injury and may have important effects on lung matrix, it does not prevent impairment of septation or induce alveolar formation during exposure to hyperoxia.