Montelukast does not protect against hyperoxia‐induced inhibition of alveolarization in newborn rats

Impaired lung development has been demonstrated in neonatal animals exposed to hyperoxia. High lung cys‐leukotriene levels may be a contributing factor towards the increase in oxygen toxicity. We investigated the effect of cysteinyl‐leukotriene inhibition using the receptor antagonist, montelukast (MK, Singulair®), on hyperoxia‐induced changes in lung parenchymal structure in neonatal rat pups. Rat pups were exposed to 21% O 2 (air) or 50% O 2 (moderate hyperoxia) from days 1–14 after birth, and were administered the cys‐leukotriene receptor antagonist MK (1 mg/kg/day) or normal saline from days 4–14. Somatic growth and morphometric measurements were done on day 15. There was a significant increase in bronchoalveolar lavage fluid cysteinyl‐leukotriene levels (+61.9%) when animals were exposed to hyperoxia. O 2 exposure significantly decreased the specific internal surface area by 13%. There was a nonsignificant 5.8% and 19.6% increase in mean chord length and mean alveolar diameter, respectively, as well as an 8.6% decrease in lung volume to body weight ratio. Inhibition of only one arm of the arachidonic‐acid cascade by MK was not sufficient to prevent these oxygen‐induced changes. Pediatr Pulmonol. 2003; 35:446–451. © 2003 Wiley‐Liss, Inc.