Timing of hyperoxic exposure during alveolarization influences damage mediated by leukotrienes

• Published in: American journal of physiology. Lung cellular and molecular physiology 2001-10, Vol.281 (4), p.799-L806
• Main Authors: Manji, Jacqueline S, O'Kelly, Cian J, Leung, Wynne I, Olson, David M
• Format: Article
• Language: English
• Subjects: Age Factors; Animals; Animals, Newborn; Cell Division - drug effects; Female; Hyperoxia - immunology; Hyperoxia - metabolism; Hyperoxia - pathology; Indoles - pharmacology; Leukotrienes - metabolism; Lipoxygenase Inhibitors - pharmacology; Male; Oxygen - pharmacology; Pulmonary Alveoli - growth & development; Pulmonary Alveoli - metabolism; Pulmonary Alveoli - pathology; Quinolines - pharmacology; Rats; Rats, Sprague-Dawley
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.2001.281.4.L799

Departments of 1  Physiology, 2  Pediatrics, and 3  Obstetrics and Gynecology and Perinatal Research Centre, University of Alberta, Edmonton, Alberta T6G 2S2, Canada Hyperoxic exposure of rat pups during alveolarization (postnatal days 4-14 ) severely retards alveolar development. Some aspects of this inhibition are mediated by leukotrienes (LTs) and may be time sensitive. We determined 1 ) the effects of exposure to hyperoxia (O 2 ) during discrete periods before and during alveolarization on developing alveoli and 2 ) whether a relationship exists between O 2 and LTs in these periods. Pups were exposed to >95% O 2 from days 1  to 4 , 4  to 9 , 9  to 14 , or 4  to 14  in the absence and presence of the LT synthesis inhibitor MK-0591. Both the level of in vitro lung tissue LT output on days 4 , 9 , and 14  and the degree of alveolarization on day 14  were determined. Pups exposed to O 2 from days 4  to 9   had a more profound inhibition of alveolarization on day 14  compared with those exposed to O 2 from days 1  to 4  or 9  to 14 . Peptido-LT levels were significantly higher in pups exposed to O 2 on days 9  and 14  compared with pups in air and returned to normal once normoxia was restored. LT inhibition from days 4  to 14 , 4  to 9 , or 9  to 14  in pups exposed to O 2 from days 4  to 14  prevented the O 2 -induced inhibition of alveolarization. These data suggest that developing alveoli are sensitive to LTs shortly before and after day 9 , significantly retarding certain parameters of alveolarization on day 14 . We conclude that some of the effects of O 2 are not uniform throughout different stages of alveolarization and that this is likely related to the timing of LT exposure. MK-0591; morphometry; 5-lipoxygenase-activating protein