title: Disparate IL-1beta and iNOS gene expression in the aorta and pulmonary artery after endotoxemia.
abstract: BACKGROUND
  Endotoxemia causes paradoxical effects on the systemic and pulmonary vasculature, resulting in systemic hypotension and increased pulmonary artery pressure. The local production of inflammatory mediators may have important effects on vascular tissue function. The purpose of this study was to delineate differences in function and the expression of tissue cytokine genes in the aorta and pulmonary artery after endotoxemia.
  
  
  METHODS
  Thoracic aorta and pulmonary artery branches were isolated from adult Sprague- Dawley rats (n = 4-6/group) 6 h after intraperitoneal injection of lipopolysaccharide (Salmonella typhimurium, 20 mg/kg) or vehicle (1.0 mL of saline). Arteries were suspended in perfused organ baths for measurement of isometric force transduction, and dose-response curves to phenylephrine (0.01-10 micromol/L), acetylcholine (0.01-10 micromol/L), and sodium nitroprusside (0.001-10 micromol/L) were generated. The vascular segments were also assessed for expression of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, and inducible nitric oxide synthase (iNOS) messenger RNA (mRNA) by semiquantitative reverse transcriptase- polymerase chain reaction.
  
  
  RESULTS
  Endotoxemia resulted in decreased contractility of the aorta (508.63 +/- 81.89 mg vs. 2544.16 +/- 142.05 mg in the vehicle group) and pulmonary artery (352.50 +/- 38.11 mg vs. 535.83 +/- 45.51 mg in the vehicle group) and decreased endothelium-dependent pulmonary artery relaxation (52.86 +/- 5.63% vs. 80.58 +/- 6.39% in the vehicle group). Expression of IL-1beta and iNOS mRNA by the pulmonary artery, but not the aorta, increased significantly in the endotoxintreated animals. Interleukin-6 was increased in both the pulmonary artery and the aorta during endotoxemia, whereas TNF concentrations were unchanged.
  
  
  CONCLUSIONS
  Endotoxemia may cause aortic hypocontractility and impaired endothelium-dependent pulmonary artery vasorelaxation. Expression of inflammatory genes in vascular tissue may be site-specific and may contribute to the functional derangements associated with sepsis.
authors.affiliation: Department of Surgery, Indiana University Medical Center, Indianapolis, Indiana 46202, USA.
authors.forename: Ben M
authors.initials: BM
authors.lastname: Tsai
authors.forename: Meijing
authors.initials: M
authors.lastname: Wang
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Pitcher
authors.forename: Ajay
authors.initials: A
authors.lastname: Kher
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Meldrum
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000502:physiology*; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000378:metabolism* / Q000503:physiopathology; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D011651:Pulmonary Artery / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D014661:Vasoconstriction / Q000502:physiology*
chemical_list: D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II