title: Distant effects of nitric oxide inhalation in endotoxemic pigs.
abstract: OBJECTIVE
  Inhalation of nitric oxide (INO) has distant effects. By a blood- borne factor, INO down-regulates endogenous nitric oxide production in healthy pig lungs, resulting in vasoconstriction in lung regions not directly reached by INO. The aim of this study was to investigate whether INO has distant effects in endotoxemic pig lungs. The hypothesis was that INO down-regulates endogenous NO production in lung regions not reached by INO.
  
  
  METHODS
  Prospective, randomized animal study.
  
  
  METHODS
  University hospital research laboratory.
  
  
  METHODS
  Twenty-two pairs of domestic pigs.
  
  
  METHODS
  Cross-circulation was established in 22 pairs of anesthetized pigs. Nine pairs received endotoxin (control group) and 13 pairs received endotoxin, with one pig inhaling NO (80 ppm) and one pig receiving blood from that pig (NO-blood recipient group).
  
  
  RESULTS
  NO in exhaled air, NO synthase activity in lung tissue, endothelin-1 in the blood, ETA and ETB receptor immunoreactivity in lung tissue, vital parameters, and blood gases were measured. Endotoxin per se increased NO in exhaled air by 100% compared to baseline (control group). In the NO-blood recipient group, i.e., pigs receiving blood from the NO-inhaling pigs, NO in exhaled air increased by 300% (p = .03). The Ca-dependent NO synthase activity was higher in these pigs (p = .02), indicating increased endogenous NO production. The ET B receptor immunoreactivity was higher in the NO-blood recipient group (p = .004).
  
  
  CONCLUSIONS
  As opposed to findings in healthy pigs, INO in endotoxemic pigs causes an increase in endogenous NO production in lung regions not reached by INO. Increased NO production in nonventilated lung regions may cause vasodilatation, counteracting the INO-induced increase in blood flow to the ventilated lung regions.
authors.affiliation: Department of Anesthesiology and Intensive Care, Uppsala University, Uppsala.
authors.forename: Manja C A
authors.initials: MC
authors.lastname: Nilsson
authors.forename: Kristina
authors.initials: K
authors.lastname: Hambraeus-Jonzon
authors.forename: Kristina
authors.initials: K
authors.lastname: Hambraeus-Jonon
authors.forename: Marco
authors.initials: M
authors.lastname: Lattuada
authors.forename: Luni
authors.initials: L
authors.lastname: Chen
authors.forename: Ren
authors.initials: R
authors.lastname: Li
authors.forename: Kjell
authors.initials: K
authors.lastname: Alving
authors.forename: Peter
authors.initials: P
authors.lastname: Wiklund
authors.forename: Goran
authors.initials: G
authors.lastname: Hedenstierna
authors.forename: Filip
authors.initials: F
authors.lastname: Fredén
mesh_terms: D000280:Administration, Inhalation; D000704:Analysis of Variance; D000818:Animals; D001784:Blood Gas Analysis; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000097:blood* / Q000378:metabolism; D019446:Endotoxemia / Q000188:drug therapy* / Q000401:mortality; D004731:Endotoxins / Q000494:pharmacology; D004926:Escherichia coli; D006439:Hemodynamics / Q000187:drug effects; D009569:Nitric Oxide / Q000494:pharmacology*; D011336:Probability; D011652:Pulmonary Circulation / Q000187:drug effects*; D011863:Radioimmunoassay; D011897:Random Allocation; D012016:Reference Values; D015996:Survival Rate; D034421:Sus scrofa; D013552:Swine
chemical_list: D019332:Endothelin-1; D004731:Endotoxins; D009569:Nitric Oxide