title: Modulation of hypoxic pulmonary vasoconstriction is time and nitric oxide dependent in a peritonitis model of sepsis.
abstract: OBJECTIVE
  This study assessed modulation of hypoxic pulmonary vasoconstriction (HPV) in isolated perfused rat lungs during sepsis induced by cecal ligation and perforation (CLP) at different times and its relationship to nitric oxide synthases (NOS).
  
  
  METHODS
  Prospective controlled trial in a university research laboratory.
  
  
  METHODS
  102 male Sprague-Dawley rats.
  
  
  METHODS
  Groups 1-3 received sham laparotomy 6 h before lung isolation: group 1, only laparotomy; group 2, concurrently L- N6-(1-iminoethyl)-lysine (L-NIL, 3 mg/kg); group 3, concurrently N(Omega)-nitro-L-arginine methylester (L-NAME, 5 mg/kg). Groups 4-6 received CLP 6 h before lung isolation: group 4, only CLP; group 5, concurrently L-NIL; group 6, concurrently L-NAME. The same experiments were carried out with sham and CLP treatment for 24 h (groups 7-12). Exhaled NO from rats' lungs was measured after anesthesia and tracheostomy. After the pulmonary circuit was isolated and perfused, angiotensin II (0.1 microg) was injected into the inflow tract. The lungs were ventilated with the hypoxic mixture (HPV, 3% O2) for 10 min and then again with the normoxic mixture (21% O2) for an equal period. Changes in perfusion pressure were measured. Endothelial (eNOS) and inducible NOS (iNOS) expression of the lungs was determined.
  
  
  RESULTS
  Treatment with L-NAME but not L-NIL increased HPV in sham lungs. HPV was unaltered after CLP 6 h and decreased after CLP 24 h compared to sham. In CLP animals eNOS protein expression was reduced whereas iNOS expression was increased compared to sham animals. Exhaled NO, reflecting NOS activity was twice as high in the CLP 24 h group than in the CLP 6 h group.
  
  
  CONCLUSIONS
  In the CLP sepsis model modulation of HPV was time-dependent. In addition, vasoconstriction to hypoxic stimuli was dependent on NOS activity.
authors.affiliation: Department of Anesthesiology and Intensive Care, University of Münster, 48149 Münster, Germany. fischla@hotmail.com
authors.forename: L G
authors.initials: LG
authors.lastname: Fischer
authors.forename: H
authors.initials: H
authors.lastname: Freise
authors.forename: J-H
authors.initials: JH
authors.lastname: Hilpert
authors.forename: D
authors.initials: D
authors.lastname: Wendholt
authors.forename: S
authors.initials: S
authors.lastname: Lauer
authors.forename: H
authors.initials: H
authors.lastname: Van Aken
authors.forename: A W
authors.initials: AW
authors.lastname: Sielenkämper
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology; D066298:In Vitro Techniques; D008168:Lung / Q000098:blood supply* / Q000378:metabolism / Q000503:physiopathology; D008239:Lysine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D010538:Peritonitis / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D011446:Prospective Studies; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000150:complications; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
chemical_list: D004791:Enzyme Inhibitors; C090663:N(6)-(1-iminoethyl)lysine; D000804:Angiotensin II; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; D008239:Lysine; D019331:NG-Nitroarginine Methyl Ester