Biphasic response to lipopolysaccharide from E. coli in the isolated ventilated blood-perfused rat lung.
We characterised early circulatory and respiratory responses to lipopolysaccharide from E. coli (LPS, serotype 0127:B8) in the isolated, ventilated and perfused rat lung preparation. Lungs were isolated from anaesthetised Wistar rats and perfused with full blood, platelet rich plasma (PRP), platelet poor plasma (PPP) or Krebs-Henseleit solution (KH). LPS (300 microg/ml) injected into the blood-perfused lung induced a characteristic biphasic response consisting of an immediate, transient decrease in respiratory tidal volume and an increase in pulmonary perfusion pressures followed by a delayed decrease in respiratory tidal volume. An immediate respiratory/circulatory response to LPS was of considerable magnitude only in full blood-perfused lung whereas the delayed response was fully expressed irrespective whether blood, PRP, PPP or KH was used for the lung perfusion. Immediate respiratory/circulatory response was inhibited by WEB 2170 (100 microM), a PAF receptor antagonist, and by camonagrel (300 microM), a TXA2 synthase inhibitor, but not by MK 571 (100 microM), a cysteinyl leukotriene receptor antagonist. Delayed respiratory response was inhibited by camonagrel only. In summary, we demonstrated that the immediate coupled respiratory/circulatory response is mediated by blood cell-derived PAF and TXA2 whereas the delayed uncoupled respiratory response is mediated by lung parenchyma-derived TXA2.
Chlopicki
S
S
Department of Pharmacology, Jagiellonian University Medical College, Krakow, Poland. mfschlop@cyf-kr.edu.pl
Bartuś
J B
JB
Gryglewski
R J
RJ
D000818:Animals; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D001993:Bronchodilator Agents / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli / Q000737:chemistry*; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects*; D010477:Perfusion; D010972:Platelet Activating Factor / Q000502:physiology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012119:Respiration / Q000187:drug effects; D013928:Thromboxane A2 / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D014662:Vasoconstrictor Agents; D013928:Thromboxane A2