title: Evidence against a pathogenetic role for endothelin in pre-eclampsia.
abstract: OBJECTIVE
  To assess whether increased placental or systemic endothelin synthesis has a pathogenic role in pre-eclampsia (gestational proteinuric hypertension).
  
  
  METHODS
  Prospective observations study.
  
  
  METHODS
  19 women with pre-eclampsia and 10 healthy pregnant women were studies. All were in the last trimester.
  
  
  METHODS
  Preproendothelin-1 gene expression by Northern blot analysis and generation of endothelin-1 precursor, big-endothelin-1, and endothelin isoforms, namely endothelin-1, 2 and 3, were assessed by specific radio-immunoassays, in placental tissue. Plasma endothelin-1 levels and urinary excretion of big-endothelin-1 and endothelin-1 were measured.
  
  
  RESULTS
  Placental preproendothelin-1 gene expression and immunoreactive big-endothelin-1 and endothelin-1, 2 and 3, were comparable in placental tissue from pre-eclamptic and normal pregnant women. Plasma levels of endothelin-1 did not differ between pre-eclamptic and normal pregnancies. In contrast, urinary excretion of endothelin-1, which is likely to reflect the renal synthesis of the peptide, was significantly decreased in pre-eclamptic, as compared with normal pregnant women. This was not due to a decreased renal generation of endothelin-1 precursor, since urinary excretion of big-endothelin-1 did not differ between pre-eclamptic and normal pregnancies. These data suggest an increased renal endothelin-1 breakdown in pre-eclampsia.
  
  
  CONCLUSIONS
  Endothelin is unlikely to play a role in the pathogenesis of pre-eclampsia. Instead, an increased renal breakdown may have a role in limiting the negative effects of other vasoactive factors on the renal circulation.
authors.affiliation: Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Benigni
authors.forename: S
authors.initials: S
authors.lastname: Orisio
authors.forename: F
authors.initials: F
authors.lastname: Gaspari
authors.forename: T
authors.initials: T
authors.lastname: Frusca
authors.forename: G
authors.initials: G
authors.lastname: Amuso
authors.forename: G
authors.initials: G
authors.lastname: Remuzzi
mesh_terms: D000328:Adult; D016232:Endothelins / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism; D010920:Placenta / Q000378:metabolism; D011225:Pre-Eclampsia / Q000209:etiology / Q000378:metabolism* / Q000652:urine; D011247:Pregnancy; D011446:Prospective Studies; D012313:RNA / Q000378:metabolism
chemical_list: D016232:Endothelins; D012313:RNA