title: Effect of Intralipid on hypoxic and angiotensin-II induced pulmonary vasoconstriction in the isolated rat lung.
abstract: OBJECTIVE
  Lipid infusions are reported to cause hypoxemia by increasing intrapulmonary shunt fraction. However, the mechanism by which they worsen gas exchange is unknown. We hypothesized that a reduction in hypoxic pulmonary vasoconstriction, caused by lipid infusion, could be the cause of increased shunt.
  
  
  METHODS
  A prospective, controlled laboratory study.
  
  
  METHODS
  A postgraduate teaching hospital laboratory.
  
  
  METHODS
  Male Wistar rats weighing 250 to 300 g.
  
  
  METHODS
  Four separate series of experiments were performed: a) The pulmonary vasopressor response to angiotensin-II was compared before and after adding either 0.9% sodium chloride (control n = 5) or 20 microL of Intralipid (n = 8). b) The pulmonary vasopressor response to hypoxia (FIO2 of 0.3) was compared before and after either 0.9% sodium chloride (control n = 5) or 20 microL of Intralipid (n = 8). c) 1 microM of indomethacin was added before either 0.9% sodium chloride (control n = 5) or Intralipid (n = 5) and the hypoxic pulmonary vasoconstriction response was compared. d) 10(-3) M L-monomethyl-n-arginine was added before 20 microL of Intralipid and the hypoxic pulmonary vasoconstriction response was compared (n = 5).
  
  
  RESULTS
  Changes in pulmonary arterial pressure were measured before and after interventions. Intralipid reduced the angiotensin-II pressor response by 36 +/- 3% (p = .005) and the hypoxic pulmonary vasoconstriction response by 50 +/- 2% (p = .0003). This action was not blocked by pretreatment with either indomethacin or L-monomethyl-n-arginine.
  
  
  CONCLUSIONS
  Intralipid reduces the hypoxic pulmonary vasoconstriction response in the isolated, blood perfused rat lung. This action is nonspecific, as shown by a similar reduction in the pulmonary pressor response to angiotensin-II. Pharmacologic blockade of prostaglandin release, by indomethacin, and nitric oxide release, by L-monomethyl-n-arginine did not prevent the reduction in hypoxic pulmonary vasoconstriction, thereby suggesting that neither agent mediates the lipid-induced change in pulmonary vasoreactivity.
authors.affiliation: Department of Anaesthesia and Intensive Care, National Heart and Lung Institute, Royal Brompton and National Heart and Lung Hospital, London, UK.
authors.forename: S V
authors.initials: SV
authors.lastname: Baudouin
authors.forename: M
authors.initials: M
authors.lastname: Messent
authors.forename: T W
authors.initials: TW
authors.lastname: Evans
mesh_terms: D000704:Analysis of Variance; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004347:Drug Interactions; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology*; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects*; D019323:omega-N-Methylarginine
chemical_list: D005217:Fat Emulsions, Intravenous; D011453:Prostaglandins; D000804:Angiotensin II; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D007213:Indomethacin