title: Endotoxin induces differentiated contractile responses in porcine pulmonary arteries and veins.
abstract: OBJECTIVE
  Sepsis-induced lung injury is characterized by pulmonary hypertension, edema and deteriorated gas exchange. As in vivo studies have indicated that bacterial endotoxin predominantly induces a pulmonary venous constriction, we aimed to investigate effects of endotoxin on isolated porcine pulmonary vessels.
  
  
  METHODS
  Pulmonary arteries and veins were examined using in vitro isometric force recordings. Endothelin-receptor protein expression and distribution were analyzed by Western blot and immunohistochemistry. Freshly isolated preparations and vessels incubated (24 h) with/without endotoxin (10 μg·ml(-1)) were compared. The contractile responses to phenylephrine, UK14.304, U46619, PGF(2α), endothelin-1 (ET-1) and sarafotoxin were recorded, as well as the relaxation in response to acetylcholine, isoproterenol and nitroprusside.
  
  
  RESULTS
  In freshly isolated vessels, phenylephrine-induced contractions had a 5-times larger amplitude in arteries than in veins. The amplitude of the contractions in response to sarafotoxin was nearly 2 times larger in veins than in arteries, but there was no difference in responses to ET-1. Endotoxin markedly reduced phenylephrine-induced contractions in both arteries and veins, whereas the responses to ET-1 and sarafotoxin were augmented in veins only. No apparent changes in ET receptor expression or distribution were detected with Western blot or immunohistochemistry.
  
  
  CONCLUSIONS
  Endotoxin differentially and selectively alters the contractile responses of porcine pulmonary vessels in vitro, towards a situation where the α-1 adrenergic responses of arteries are attenuated and the ET responses of veins are augmented. In situations with high adrenergic activity and high circulating ET levels, such as sepsis, these results may provide a mechanism contributing to pulmonary hypertension and edema formation.
authors.affiliation: Section of Anaesthesiology and Intensive Care Medicine, Karolinska Institutet, Stockholm, Sweden. bjorn.persson@karolinska.se
authors.forename: Björn P
authors.initials: BP
authors.lastname: Persson
authors.forename: Piet J M
authors.initials: PJ
authors.lastname: Boels
authors.forename: Cecilia
authors.initials: C
authors.lastname: Lövdahl
authors.forename: Patrik
authors.initials: P
authors.lastname: Rossi
authors.forename: Anders
authors.initials: A
authors.lastname: Arner
authors.forename: Anders
authors.initials: A
authors.lastname: Oldner
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000494:pharmacology*; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D009213:Myography; D009924:Organ Culture Techniques; D011651:Pulmonary Artery / Q000187:drug effects* / Q000378:metabolism; D011667:Pulmonary Veins / Q000187:drug effects* / Q000378:metabolism; D017466:Receptors, Endothelin / Q000187:drug effects / Q000378:metabolism; D034421:Sus scrofa; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D004731:Endotoxins; D017466:Receptors, Endothelin; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents