Document Detail


Inhaled nitric oxide attenuates hyperoxic lung injury in lambs.
MedLine Citation:
PMID:  16327001     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cytochrome P450 (CYP) inhibition with cimetidine reduces hyperoxic lung injury in young lambs. Nitric oxide (NO), also a CYP inhibitor, has been shown to either aggravate or protect against oxidant stress depending on experimental context. The objective of this study was to determine whether NO, like cimetidine, would protect young lambs against hyperoxic lung injury, and whether its effect was associated with CYP inhibition. Three groups of lambs were studied: 1) room air exposure, 2) >95% O2, and 3) >95% O2 plus inhaled NO. After 72 h, hyperoxia alone resulted in a significant increase in arterial P(CO2) and number of polymorphonuclear leukocytes in bronchoalveolar lavage (BAL), and a significant decrease in arterial/alveolar O2 tension (a/A). The addition of inhaled NO significantly decreased the hypercarbia and BAL polymorphonuclear cellular response associated with hyperoxia but had no beneficial effect on a/A ratio. There were no significant differences in F2-isoprostanes or isofurans (markers of lipid peroxidation) measured in BAL or lung tissue among study groups. No intergroup differences were detected in BAL epoxyeicosatrienoic acid levels (index of CYP activity). The results of this study indicate that hypercarbia and inflammation accompanying hyperoxic lung injury in young lambs can be attenuated by inhaled NO. However, this study provides no direct evidence that NO is inhibiting CYP-mediated oxidant lung injury.
Authors:
Robert B Cotton; Håkan W Sundell; Darryl C Zeldin; Jason D Morrow; L Jackson Roberts; Tom A Hazinski; Amy B Law; Steven Steele
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural     Date:  2005-12-02
Journal Detail:
Title:  Pediatric research     Volume:  59     ISSN:  0031-3998     ISO Abbreviation:  Pediatr. Res.     Publication Date:  2006 Jan 
Date Detail:
Created Date:  2005-12-28     Completed Date:  2006-02-01     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0100714     Medline TA:  Pediatr Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  142-6     Citation Subset:  IM    
Affiliation:
Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA. robert.cotton@vanderbilt.edu
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MeSH Terms
Descriptor/Qualifier:
Administration, Inhalation
Animals
Animals, Newborn
Bronchoalveolar Lavage Fluid / chemistry,  cytology
Cytochrome P-450 Enzyme System / antagonists & inhibitors
F2-Isoprostanes / analysis
Hyperoxia / complications*
Leukocytes / cytology
Nitric Oxide / administration & dosage,  therapeutic use*
Oxidative Stress*
Pneumonia / enzymology,  etiology,  prevention & control*
Sheep, Domestic
Grant Support
ID/Acronym/Agency:
DK26657/DK/NIDDK NIH HHS; GM15431/GM/NIGMS NIH HHS; GM42056/GM/NIGMS NIH HHS; HL56697/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/F2-Isoprostanes; 10102-43-9/Nitric Oxide; 9035-51-2/Cytochrome P-450 Enzyme System

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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