Inhaled nitric oxide attenuates hyperoxic lung injury in lambs.
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.
Cotton
Robert B
RB
Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA. robert.cotton@vanderbilt.edu
Sundell
Håkan W
HW
Zeldin
Darryl C
DC
Morrow
Jason D
JD
Roberts
L Jackson
LJ
Hazinski
Tom A
TA
Law
Amy B
AB
Steele
Steven
S
D000280:Administration, Inhalation; D000818:Animals; D000831:Animals, Newborn; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D065607:Cytochrome P-450 Enzyme Inhibitors; D028441:F2-Isoprostanes / Q000032:analysis; D018496:Hyperoxia / Q000150:complications*; D007962:Leukocytes / Q000166:cytology; D009569:Nitric Oxide / Q000008:administration & dosage / Q000627:therapeutic use*; D018384:Oxidative Stress; D011014:Pneumonia / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D034561:Sheep, Domestic
D065607:Cytochrome P-450 Enzyme Inhibitors; D028441:F2-Isoprostanes; D009569:Nitric Oxide