Clearance Mechanisms of Atrial and Brain Natriuretic Peptides in Rats

Yukiya Hashimoto, Kazuwa Nakao, Norio Hama, Hiroo Imura, Sachiyo Mori, Masayuki Yamaguchi, Masato Yasuhara, Ryohei Hori*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

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 α-rat atrial natriuretic peptide (α-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)-rANP4−23-NH2 [C-ANF4−23]. On the other hand, the clearance of α-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-ANF4−23 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 α-rANP. The effect of phosphoramidon on the clearance of rBNP was not significant and was similar to that of C-ANF4−23. These results suggest that clearance receptor is involved in the clearance of the physiological levels of α-rANP and that NEP plays a major role in the clearance of a pharmacological dose of α-rANP, at which clearance receptors are thought to be saturated, and also indicate a pharmacokinetic difference between α-rANP and rBNP.

Original languageEnglish
Pages (from-to)60-64
Number of pages5
JournalPharmaceutical Research
Volume11
Issue number1
DOIs
StatePublished - 1994/01

Keywords

  • atrial natriuretic peptide
  • brain natriuretic peptide
  • clearance receptor
  • neutral endopeptidase
  • phosphoramidon

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

Fingerprint

Dive into the research topics of 'Clearance Mechanisms of Atrial and Brain Natriuretic Peptides in Rats'. Together they form a unique fingerprint.

Cite this