AJP - Lung Cellular and Molecular Physiology, Vol 272, Issue 3 433-L441, Copyright © 1997 by American Physiological Society

ARTICLES

Leukotrienes are indicated as mediators of hyperoxia-inhibited alveolarization in newborn rats

V. Boros, J. S. Burghardt, C. J. Morgan and D. M. Olson
Department of Pediatrics, The University of Alberta, Edmonton, Canada.

We investigated the role of leukotrienes (LT) in hyperoxia-induced changes in lung parenchyma in neonatal rat pups. Rat pups were exposed to 21% O(2) (air) or >95% O(2) from days 4 to 14 after birth and were administered the 5-lipoxygenase (5-LO) inhibitor and LTD4 receptor antagonist Wy-50295, 5-LO-activating protein 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 O(2) compared with air-exposed animals. Both Wy-50295 and MK-0591 significantly lowered (P < 0.05) peptido-LT output in O(2)-exposed animals. The 6-ketoprostaglandin F(1alpha) output was increased similarly in both vehicle- and drug-treated O(2)-exposed animals. O(2) exposure also caused a significant increase in bronchoalveolar lavage fluid protein and extravascular lung water that could not be ameliorated by Wy-50295 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-exposed animals, was prevented by both Wy-50295 and MK-0591. Although hyperoxia had no effect on septal thickness, Wy-50295 caused significant thickening in both air- and O(2)-exposed pups. Our studies provide evidence that hyperoxia-induced peptido-LT may mediate O(2)-induced inhibition of alveolarization and that this is not caused by an arachidonic acid shunt to cyclooxygenase.

This article has been cited by other articles:

				G. E. Hosford and D. M. Olson Effects of hyperoxia on VEGF, its receptors, and HIF-2{alpha} in the newborn rat lung Am J Physiol Lung Cell Mol Physiol, July 1, 2003; 285(1): L161 - L168. [Abstract] [Full Text] [PDF]

				S. Dauger, L. Ferkdadji, G. Saumon, G. Vardon, M. Peuchmaur, C. Gaultier, and J. Gallego Neonatal Exposure to 65% Oxygen Durably Impairs Lung Architecture and Breathing Pattern in Adult Mice Chest, February 1, 2003; 123(2): 530 - 538. [Abstract] [Full Text] [PDF]

				J. S. Manji, C. J. O'Kelly, W. I. Leung, and D. M. Olson Timing of hyperoxic exposure during alveolarization influences damage mediated by leukotrienes Am J Physiol Lung Cell Mol Physiol, October 1, 2001; 281(4): L799 - L806. [Abstract] [Full Text] [PDF]