Clearance mechanisms of atrial and brain natriuretic peptides in rats

Pharm Res. 1994 Jan;11(1):60-4. doi: 10.1023/a:1018941626731.


To assess clearance mechanisms of atrial and brain natriuretic peptides in the circulation, we examined the effects of a neutral endopeptidase (NEP) inhibitor and a clearance receptor ligand on plasma concentrations of the peptides in normal rats. Plasma concentrations of endogenous alpha-rat atrial natriuretic peptide (alpha-rANP) were not significantly elevated by intravenous infusion of a NEP inhibitor, phosphoramidon, but were elevated threefold by intravenous infusion of a clearance receptor ligand, des(Gln18-Gly22)-rANP(4-23)-NH2 [C-ANF(4-23)]. On the other hand, the clearance of alpha-rANP given intravenously at the pharmacological dose, 600 pmol/min/kg for 2 min, was decreased to one-third by the administration of phosphoramidon, although the administration of C-ANF(4-23) did not significantly decrease the clearance. The clearance of rat brain natriuretic peptide (rBNP) given at 600 pmol/min/kg for 2 min was approximately 38% lower than that of alpha-rANP. The effect of phosphoramidon on the clearance of rBNP was not significant and was similar to that of C-ANF(4-23). These results suggest that clearance receptor is involved in the clearance of the physiological levels of alpha-rANP and that NEP plays a major role in the clearance of a pharmacological dose of alpha-rANP, at which clearance receptors are thought to be saturated, and also indicate a pharmacokinetic difference between alpha-rANP and rBNP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Atrial Natriuretic Factor / blood
  • Atrial Natriuretic Factor / pharmacokinetics*
  • Blood Proteins / metabolism
  • Cattle
  • Glycopeptides / pharmacology
  • Humans
  • Male
  • Microvilli / metabolism
  • Molecular Sequence Data
  • Natriuretic Peptide, Brain
  • Neprilysin / antagonists & inhibitors
  • Nerve Tissue Proteins / blood
  • Nerve Tissue Proteins / pharmacokinetics*
  • Peptide Fragments / blood
  • Peptide Fragments / pharmacokinetics*
  • Protein Binding
  • Rats
  • Rats, Wistar
  • Recombinant Proteins / pharmacokinetics


  • Blood Proteins
  • Glycopeptides
  • Nerve Tissue Proteins
  • Peptide Fragments
  • Recombinant Proteins
  • atrial natriuretic factor (4-23)NH2, de-Gln(18)-de-Ser(19)-de-Gly(20,22)-de-Leu(21)-
  • Natriuretic Peptide, Brain
  • Atrial Natriuretic Factor
  • Neprilysin
  • phosphoramidon