title: Endotoxemia augments neurogenic plasma exudation in guinea pig lungs.
abstract: BACKGROUND
  Lipopolysaccharide (LPS) is closely associated with the development of infection-induced deleterious pulmonary reactions. In this study, we investigated the enhancement effects of LPS on tachykinin-mediated plasma exudation in the lungs of guinea pigs. The role of oxidants was also explored.
  
  
  METHODS
  Intravenous LPS (100 mu kg-1) or its vehicle was administered 0 to 3 hours prior to bilateral electrical or sham stimulation of the cervical vagus nerves in animals anesthetized with urethane and artificially ventilated. Plasma exudation into the lungs was assessed by measurement of extravasated 125I-albumin which had been intravenously administered before stimulation.
  
  
  RESULTS
  The plasma exudation in the lungs increased after bilateral cervical vagal stimulation. LPS alone did not induce significant plasma exudation. The vagally-mediated plasma exudation was enhanced by LPS with the peak effect 1 hour after LPS administration. LPS also enhanced exogenous substance P (10(-8) mol kg-1, i.v.)-induced plasma exudation. The vagally-induced plasma exudation was abolished by a specific neurokinin-1 (NK-1) receptor antagonist, L-732,138. The LPS-induced enhancement response was also attenuated by L-732,138. The vagally-induced plasma exudation was not affected by superoxide dismutase (SOD, 5000 U kg-1, i.p.) pretreatment. However, SOD significantly inhibited the LPS-enhanced neurogenic plasma leakage. The LPS-induced enhancement was not completely abolished by either L-732,138 or SOD pretreatment alone, but by a combination of both.
  
  
  CONCLUSIONS
  LPS augments neurogenic plasma exudation partly through NK-1 receptors to increase vascular permeability and partly via the generation of oxidative metabolites. Tachykinins released from nerve endings may contribute to endotoxin-related pulmonary inflammatory responses.
authors.affiliation: Department of Internal Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan, R.O.C.
authors.forename: S M
authors.initials: SM
authors.lastname: Lin
authors.forename: K H
authors.initials: KH
authors.lastname: Hwang
authors.forename: H C
authors.initials: HC
authors.lastname: Lin
authors.forename: C H
authors.initials: CH
authors.lastname: Wang
authors.forename: C T
authors.initials: CT
authors.lastname: Yu
authors.forename: H P
authors.initials: HP
authors.lastname: Kuo
mesh_terms: D000818:Animals; D002199:Capillary Permeability; D019446:Endotoxemia / Q000378:metabolism*; D006168:Guinea Pigs; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1 / Q000502:physiology; D013373:Substance P / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology
chemical_list: D008070:Lipopolysaccharides; D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1; D013373:Substance P; D013482:Superoxide Dismutase