Inhaled ethyl nitrite prevents hyperoxia-impaired postnatal alveolar development in newborn rats.
BACKGROUND
Inhaled nitric oxide (NO) has been used to prevent bronchopulmonary dysplasia, but with variable results. Ethyl nitrite (ENO) forms S-nitrosothiols more readily than does NO, and resists higher-order nitrogen oxide formation. Because S-nitrosylation is a key pathway mediating many NO biological effects, treatment with inhaled ENO may better protect postnatal lung development from oxidative stress than NO.


OBJECTIVE
To compare inhaled NO and ENO on hyperoxia-impaired postnatal lung development.


METHODS
We treated newborn rats beginning at birth to air or 95% O(2) +/- 0.2-20.0 ppm ENO for 8 days, or to 10 ppm NO for 8 days. Pups treated with the optimum ENO dose, 10 ppm, and pups treated with 10 ppm NO were recovered in room air for 6 more days.


RESULTS
ENO and NO partly prevented 95% O(2)-induced airway neutrophil influx in lavage, but ENO had a greater effect than did NO in prevention of lung myeloperoxidase accumulation, and in expression of cytokine-induced neutrophil chemoattractant-1. Treatment with 10 ppm ENO, but not NO, for 8 days followed by recovery in air for 6 days prevented 95% O(2)-induced impairments of body weight, lung compliance, and alveolar development.


CONCLUSIONS
Inhaled ENO conferred protection superior to inhaled NO against hyperoxia-induced inflammation. ENO prevented hyperoxia impairments of lung compliance and postnatal alveolar development in newborn rats.
Auten
Richard L
RL
Division of Neonatal Medicine, Department of Pediatrics, Neonatal-Perinatal Research Institute, University Medical Center, Durham, North Carolina 27710, USA. auten@duke.edu
Mason
Stanley N
SN
Whorton
Mary H
MH
Lampe
William R
WR
Foster
W Michael
WM
Goldberg
Ronald N
RN
Li
Bo
B
Stamler
Jonathan S
JS
Auten
Kathryn M
KM
D000280:Administration, Inhalation; D000818:Animals; D000831:Animals, Newborn; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001997:Bronchopulmonary Dysplasia / Q000517:prevention & control; D004195:Disease Models, Animal; D006801:Humans; D018496:Hyperoxia / Q000188:drug therapy / Q000503:physiopathology; D007231:Infant, Newborn; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D009569:Nitric Oxide / Q000008:administration & dosage / Q000009:adverse effects; D009573:Nitrites / Q000008:administration & dosage* / Q000009:adverse effects; D018384:Oxidative Stress / Q000187:drug effects; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000254:growth & development* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D001993:Bronchodilator Agents; D009573:Nitrites; D009569:Nitric Oxide; C032712:ethyl nitrite