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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

  1. Thomas Walther1,2,*,
  2. Holger Stepan3,
  3. Kristin Pankow4,
  4. Florian Gembardt1,2,
  5. Renaldo Faber3,
  6. Heinz-Peter Schultheiss1,
  7. Wolf-Eberhard Siems4

Article first published online: 19 APR 2004

DOI: 10.1111/j.1471-0528.2004.00123.x

Issue

BJOG: An International Journal of Obstetrics & Gynaecology

BJOG: An International Journal of Obstetrics & Gynaecology

Volume 111, Issue 5, pages 452–455, May 2004

Additional Information

How to Cite

Walther, T., Stepan, H., Pankow, K., Gembardt, F., Faber, R., Schultheiss, H.-P. and Siems, W.-E. (2004), 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. BJOG: An International Journal of Obstetrics & Gynaecology, 111: 452–455. doi: 10.1111/j.1471-0528.2004.00123.x

Author Information

  1. 1

    Department of Cardiology, Benjamin Franklin Medical Center, Berlin, Germany

  2. 2

    Department of Pharmacology, Erasmus MC, Rotterdam, The Netherlands

  3. 3

    Department of Obstetrics and Gynaecology, University of Leipzig, Germany

  4. 4

    Institute of Molecular Pharmacology, Berlin-Buch, Germany

* * Correspondence: Dr T. Walther, Department of Cardiology and Pneumology, Benjamin Franklin Medical Center, Free University of Berlin, Hindenburgdamm 30, D-12200 Berlin, Germany.

Publication History

  1. Issue published online: 19 APR 2004
  2. Article first published online: 19 APR 2004

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Objectives  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.

Design  Retrospective case–control study.

Setting  Department of Obstetrics and Gynaecology, University of Leipzig, Germany.

Sample  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.

Main outcome measures  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.

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