title: Early changes in alveolar fluid clearance by nitric oxide after endotoxin instillation in rats.
abstract: Alveolar fluid clearance may be inhibited and/or stimulated under pathologic conditions. We examined the early change of alveolar fluid clearance after endotoxin instillation in adult rats. We employed electron paramagnetic resonance nitric oxide (NO) trapping technique with iron complex with N,N-diethyldithiocarbamate as an NO trapping agent. We found that lung NO signals reached the highest magnitude by 6 hours after endotoxin instillation. NO production was accompanied by increases in lung cyclic guanosine monophosphate levels. Alveolar fluid clearance decreased significantly 6 hours after the administration of the endotoxin and increased further at 24 hours. These changes were shown to be related to the function of amiloride-sensitive sodium ion channels. Treatment with gadolinium chloride and aminoguanidine significantly decreased lung NO and cyclic guanosine monophosphate levels and completely ameliorated the decrease in alveolar fluid clearance. In addition, the increase in alveolar fluid clearance at 24 hours returned to normal levels after treatment with gadolinium chloride and aminoguanidine. We found immunoreactive inducible nitric oxide synthase to be abundantly expressed in the cytoplasm of alveolar macrophages. Our results suggest that alveolar endotoxin inhibits alveolar fluid clearance at 6 hours by NO. NO is produced via inducible NO synthase in endotoxin-stimulated alveolar macrophages and was also shown to increase alveolar fluid clearance at 24 hours.
authors.affiliation: Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Tsubochi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Suzuki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kubo
authors.forename: Takaharu
authors.initials: T
authors.lastname: Ueno
authors.forename: Tetsuhiko
authors.initials: T
authors.lastname: Yoshimura
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
authors.forename: Takashi
authors.initials: T
authors.lastname: Kondo
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004195:Disease Models, Animal; D004731:Endotoxins; D004926:Escherichia coli; D007150:Immunohistochemistry; D007322:Instillation, Drug; D008168:Lung / Q000473:pathology*; D016676:Macrophages, Alveolar / Q000201:enzymology*; D008297:Male; D009569:Nitric Oxide / Q000032:analysis / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D011336:Probability; D011654:Pulmonary Edema / Q000378:metabolism* / Q000503:physiopathology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013997:Time Factors
chemical_list: D004731:Endotoxins; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat