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Query: UMLS:C0242706 (hyperoxia)
 5,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined whether lipid mediators have a causal role in neonatal hyperoxia-induced lung damage, specifically, airway remodeling and hyperresponsiveness. Newborn rat pups were exposed to hyperoxia (> 95% O2 from Days 4 to 14 and 65% from Days 14 to 32) or normoxia. The 5-lipoxygenase inhibitor, LTD4 receptor antagonist, and inhibitor of platelet-activating factor synthesis, Wy-50,295 (30 mg/kg), or vehicle was administered daily from Days 3 to 32. Oxygen exposure significantly increased (p < 0.05) the production of one potential lipid mediator group, peptido-LTs, from explanted lung slices and large airways from 2-wk-old rat pups. At 4 wk, only the large airway tissue output showed significant elevation because of oxygen exposure. At both ages, Wy-50,295 significantly decreased (p < 0.05) the production of peptido-LTs in the lung and large airways of oxygen-exposed pups. Pulmonary function and airway wall morphometry were studied in 5-wk-old rat pups 2 to 3 d after oxygen exposure and drug administration ceased. The resistance change in response to methacholine (0 to 20 microg/kg body weight given intravenously) was greater (p < 0.02) in oxygen-exposed animals. Oxygen exposure caused significant (60% increase) smooth muscle thickening (p < 0.05). Wy-50,295 prevented the oxygen-induced airway hyperresponsiveness and smooth muscle thickening. We conclude that chronic hyperoxic exposure causes an increase in pulmonary production of at least one lipid mediator, peptido-LTs, from newborn rats and that this is associated with airway smooth muscle layer thickening and, consequently, airway hyperresponsiveness.
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PMID:Lipid mediators in oxygen-induced airway remodeling and hyperresponsiveness in newborn rats. 888 72

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.
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PMID:Leukotrienes are indicated as mediators of hyperoxia-inhibited alveolarization in newborn rats. 912