title: Increased pneumotoxicity of lipopolysaccharide from E.coli in nitric oxide deficient blood-perfused rat lungs.
abstract: Isolated lungs of Wistar rats were ventilated by air that was enriched with 5% CO2 and perfused with homologous blood in a closed circuit (9.5 +/- 1 ml/min) using Hugo Sachs apparatus type 829. Lipopolysaccharide from E.coli (LPS, serotype 0127:B8) at a selected sub-toxic concentration of 300 micrograms/ml added to recirculating blood produced a biphasic response. Instant transient increase in pulmonary arterial and venous perfusion pressures, and a decrease in air tidal volume, and fifty minutes later slowly progressing decrease in air tidal volume without changes in pulmonary haemodynamics, were observed. Inhibition of pulmonary nitric oxide synthase by instillation of NG-nitro-L-arginine methyl ester (L-NAME) at a final concentration of 300 microM to recirculating blood dramatically changed the response to LPS. In nitric oxide deficient lungs LPS caused prompt increase in arterial and venous pressures and a fall in air tidal volume with accompanying rise in airway resistance. Within 6.3 +/- 0.5 min a fulminant pulmonary oedema developed and all functions of the lung stopped abruptly. We conclude that pulmonary nitric oxide plays a defensive role in protecting rat lungs against LPS-induced injury.
authors.affiliation: Department of Pharmacology, Jagiellonian University Medical College, Cracow, Poland.
authors.forename: J B
authors.initials: JB
authors.lastname: Bartuś
authors.forename: S
authors.initials: S
authors.lastname: Chłopicki
authors.forename: R J
authors.initials: RJ
authors.lastname: Gryglewski
mesh_terms: D000818:Animals; D001794:Blood Pressure; D004926:Escherichia coli; D005260:Female; D008070:Lipopolysaccharides / Q000633:toxicity*; D008171:Lung Diseases / Q000139:chemically induced* / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D013990:Tidal Volume
chemical_list: D008070:Lipopolysaccharides; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester