title: Increased concentrations of endothelin-1 messenger RNA in tissues and endothelin-1 peptide in plasma in septic pigs: modulation by betamethasone.
abstract: OBJECTIVE
  To study the expression of preproendothelin-1 messenger RNA (mRNA) in tissue after Escherichia coli lipopolysaccharide challenge and to evaluate the possible effects of betamethasone both regarding endothelin-1 production as well as hemodynamic and vascular effects during E. coli lipopolysaccharide infusion in pigs in vivo.
  
  
  METHODS
  Prospective trial.
  
  
  METHODS
  Laboratory at a university medical center.
  
  
  METHODS
  Ten domestic pigs, weighing 18 to 25 kg.
  
  
  METHODS
  Anesthetized pigs were given continuous infusions of E. coli lipopolysaccharide (15 micrograms/kg/hr for 3 hrs), with or without prior treatment with betamethasone (0.5 mg/kg im 12 hrs before the start of the surgical preparation and 0.5/kg iv at the start of the preparation).
  
  
  RESULTS
  The E. coli lipopolysaccharide infusion evoked the characteristic cardiovascular changes observed in septic shock: decreased mean arterial pressure and cardiac output; increased heart rate and increased pulmonary vascular resistance. Large increases in both arterial plasma concentrations of endothelin-1-like immunoreactivity, as well as preproendothelin-1 mRNA concentrations in tissues, were also observed during the E. coli lipopolysaccharide infusion. Treatment with betamethasone significantly attenuated the E. coli lipopolysaccharide-induced increase in endothelin-1 plasma concentrations, whereas the increased mRNA concentrations were only slightly affected. Furthermore, betamethasone treatment also affected cardiovascular parameters, with significant attenuation of the E. coli lipopolysaccharide-induced increase in heart rate and a higher cardiac output after 60 mins of the E. coli lipopolysaccharide infusion. The urine production, which was markedly decreased during the E. coli lipopolysaccharide infusion, was significantly higher in the betamethasone-treated group compared with the control group.
  
  
  CONCLUSIONS
  The present results indicate that the increased concentrations of endothelin-1-like immunoreactivity that are observed in septic shock may have negative effects on both cardiovascular parameters as well as renal function, which is in agreement with a possible role for endothelin-1 in the pathogenesis of septic shock.
authors.affiliation: Division of Pharmacology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Hemsén
authors.forename: A
authors.initials: A
authors.lastname: Modin
authors.forename: E
authors.initials: E
authors.lastname: Weitzberg
mesh_terms: D000818:Animals; D001623:Betamethasone / Q000494:pharmacology*; D016232:Endothelins / Q000096:biosynthesis* / Q000097:blood; D004926:Escherichia coli; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D011863:Radioimmunoassay; D012772:Shock, Septic / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D013552:Swine
chemical_list: D016232:Endothelins; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D001623:Betamethasone