title: Relation of ANP and BNP to their N-terminal fragments in fetal circulation: evidence for enhanced neutral endopeptidase activity and resistance of BNP to neutral endopeptidase in the fetus.
abstract: OBJECTIVE
  To investigate the role of neutral endopeptidase in the turnover of atrial (ANP) and brain (BNP) natriuretic peptides and their N-terminal fragments in human fetal circulation.
  
  
  METHODS
  Retrospective case-control study.
  
  
  METHODS
  Department of Obstetrics and Gynaecology, University of Leipzig, Germany.
  
  
  METHODS
  Nine control pregnancies and nine pregnancies with rhesus isoimmunisation before and after intravascular transfusion.
  
  
  METHODS
  Natriuretic peptides and N-terminal fragments in maternal and fetal blood were measured by radio-immunoassay. Neutral endopeptidase activity was determined by HPLC.
  
  
  METHODS
  Maternal and fetal plasma concentrations of ANP, NT-proANP, BNP, NT-proBNP as well as neutral endopeptidase activity. Ratios between mature peptide and N-terminal fragment. Feto-maternal ratio.
  
  
  RESULTS
  Plasma NT-proANP concentrations are 11.7 times higher in fetal than in maternal circulation. The ANP concentration is only 1.8 times higher, probably due to doubled neutral endopeptidase activity. In contrast, both NT-proBNP and BNP are doubled in fetal plasma. Fetuses with Rh isoimmunisation had significantly higher NT-proBNP but not NT-proANP and neutral endopeptidase activity than controls. An additional volume load by intravascular transfusion did not influence N-terminal fragments or neutral endopeptidase activity.
  
  
  CONCLUSIONS
  Our study is the first to determine NT-pro natriuretic peptide concentrations and neutral endopeptidase activity in human fetuses. The results show that increased fetal neutral endopeptidase activity shifts the ANP/NT-proANP but not the BNP/NT-proBNP ratio and that the shifted BNP/NT-proBNP ratio in fetuses with Rh isoimmunisation does not involve increased neutral endopeptidase activity. These findings point to a BNP degradation that is not dependent on neutral endopeptidase.
authors.affiliation: Department of Cardiology, Benjamin Franklin Medical Center, Free University of Berlin, Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Walther
authors.forename: Holger
authors.initials: H
authors.lastname: Stepan
authors.forename: Kristin
authors.initials: K
authors.lastname: Pankow
authors.forename: Florian
authors.initials: F
authors.lastname: Gembardt
authors.forename: Renaldo
authors.initials: R
authors.lastname: Faber
authors.forename: Heinz-Peter
authors.initials: HP
authors.lastname: Schultheiss
authors.forename: Wolf-Eberhard
authors.initials: WE
authors.lastname: Siems
mesh_terms: D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D015331:Cohort Studies; D005312:Fetal Blood / Q000502:physiology; D005333:Fetus / Q000098:blood supply*; D005865:Gestational Age; D006801:Humans; D020097:Natriuretic Peptide, Brain / Q000378:metabolism*; D015260:Neprilysin / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D012189:Retrospective Studies
chemical_list: D010446:Peptide Fragments; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D015260:Neprilysin