Impaired regulation of surfactant phospholipid metabolism in the isolated rat lung after nitrogen dioxide inhalation.
Various drugs have been shown to stimulate surfactant phospholipid metabolism. Particularly beta-adrenergic agonists play an important role under physiologic conditions. For the first time we have studied whether nitrogen dioxide (NO2) inhalation alters beta-adrenergic regulation of surfactant phospholipid metabolism in the model of the isolated lung. Rats were continuously exposed in vivo to a 5 ppm NO2-containing atmosphere for 48 hr. The lungs were isolated and perfused in presence of the beta-adrenergic agonist dopexamine and surfactant metabolism was studied in three lung compartments: (1) lung lavage, (2) lung tissue, and (3) lavagable free alveolar cells. We found that (1) in normal rat lungs dopexamine increased the incorporation of palmitate and choline from the perfusate into lung lavage phospholipids. In nitrogen dioxide exposed rat lungs beta-adrenergic stimulation did not cause an increase in precursor incorporation. No significant difference in unstimulated precursor incorporation was found for normal and NO2-exposed rat lungs. (2) Lung tissue from rats exposed to NO2 showed a decreased precursor incorporation into disaturated phosphatidylcholine due to an augmented cellular pool size. (3) Lavagable alveolar cells showed an increased palmitate uptake after nitrogen dioxide inhalation and by beta-adrenergic stimulation. From these data we conclude that nitrogen dioxide inhalation impairs the beta-adrenergic regulation of surfactant phospholipid metabolism. Moreover these data underline the importance of beta-adrenergic agonists in surfactant metabolism.
Department of Internal Medicine, Philipps-University, Marburg, FRG.
R G
RG
Mengel
W
W
Bernhard
P
P
Barth
P
P
von Wichert
B
B
Müller
D000280:Administration, Inhalation; D000818:Animals; D002794:Choline / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism*; D009585:Nitrogen Dioxide / Q000008:administration & dosage / Q000633:toxicity*; D010168:Palmitates / Q000378:metabolism; D010646:Phentolamine / Q000494:pharmacology; D010743:Phospholipids / Q000378:metabolism*; D011663:Pulmonary Surfactants / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D010168:Palmitates; D010743:Phospholipids; D011663:Pulmonary Surfactants; D002794:Choline; D009585:Nitrogen Dioxide; D010646:Phentolamine