Leukotrienes are indicated as mediators of hyperoxia-inhibited alveolarization in newborn rats.. Boros, Veronika, Jacqueline S. Burghardt, Catherine J. Morgan, and David M. Olson. Departments of Pediatrics, Physiology, and Obstetrics and Gynecology, Perinatal Research Centre, The University of Alberta, Edmonton, Alberta, Canada and the Department of Pediatrics, Szent Janos Hospital, Budapest, Hungary
APStracts 3:0213L, 1996.
We investigated the role of leukotrienes (LTs) in hyperoxia-induced changes in lung parenchyma in neonatal rat pups. Rat pups were exposed to 21% O2 (air) or >95% O2 from days 4 to 14 after birth and were administered the 5-lipoxygenase (5-LO) inhibitor and LTD4 receptor antagonist, Wy-50,295, 5-LO activating protein (FLAP) inhibitor, MK-0591, or vehicle from days 3 to 14. All measurements were done on days 12-14. There was a significant (p<0.05) increase in peptido-LT output from lung slices of animals exposed to oxygen compared to air animals. Both Wy-50,295 and MK-0591 significantly lowered (p<0.05) peptido-LT output in oxygen exposed animals. 6 -keto prostaglandin F1[alpha] output was increased similarly in both vehicle and drug treated oxygen exposed animals. Oxygen exposure also caused a significant increase in bronchoalveolar lavage fluid protein and extravascular lung water that could not be ameliorated by Wy -50,295 or MK-0591. Hyperoxia-induced inhibition of alveolarization, indicated by a significantly (p<0.05) lower parenchymal tissue density, specific internal surface area, and airspace perimeter to area ratio, and a significantly (p<0.05) higher mean linear intercept and airspace unit volume than air animals, was prevented by both Wy-50,295 and MK-0591. While hyperoxia had no effect on septal thickness, Wy-50,295 caused significant thickening in both air- and O2-exposed pups. Our studies provide evidence that hyperoxia-induced peptido-LTs may mediate oxygen-induced inhibition of alveolarization and that this is not due to an arachidonic acid shunt to cyclooxygenase. 

Received 2 May 1996; accepted in final form 30 October 1996.
APS Manuscript Number L131-6.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996