Role of natriuretic peptide clearance receptor in in vivo control of C- type natriuretic peptide

R. R. Brandt, D. M. Heublein, L. L. Aarhus, J. A. Lewicki, John C Jr. Burnett

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

C-type natriuretic peptide (CNP) is a newly described 22-amino acid peptide of endothelial cell origin, which has selective cardiovascular actions and is structurally related to atrial natriuretic peptide (ANP). Recent in vitro studies have demonstrated that an important regulatory pathway for the clearance of natriuretic peptides involves binding to a common clearance receptor [natriuretic peptide C receptor (NPR-C)]. Although CNP has also been identified as a ligand for NPR-C in binding assays, no studies have defined the in vivo interaction of CNP with NPR-C. CNP (10 ng · kg-1 · min-1) followed by C-ANP-(4-23), a specific ligand for NPR-C blockade, was infused intravenously in two groups (both n = 7) of anesthetized dogs at two different doses (0.1 or 1.0 μg · kg-1 · min-1) to permit calculation of total metabolic clearance rate (TMCR). C-ANP- (4-23) increased circulating CNP and reduced TMCR in both groups. Pulmonary metabolic clearance rate was negative at baseline, suggesting a net secretion of CNP across the lung, which was increased during CNP infusion and was abolished with NPR-C blockade. Renal and femoral metabolic clearance rates were positive at baseline and increased with CNP infusion. A decrease in cardiac output and cardiac filling pressures in response to CNP administration was potentiated by NPR-C blockade. We conclude that 1) circulating CNP achieved by CNP infusion is regulated by NPR-C in vivo, 2) the pulmonary circulation is a possible site of CNP secretion, 3) the renal and peripheral circulations are sites of CNP clearance, and 4) NPR-C blockade potentiates the selective cardiovascular actions of CNP.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume269
Issue number1 38-1
StatePublished - 1995

Fingerprint

C-Type Natriuretic Peptide
natriuretic peptides
Natriuretic Peptides
Peptide Receptors
receptors
Metabolic Clearance Rate
atrial natriuretic peptide
lungs
Ligands
Lung
Pulmonary Circulation
Renal Circulation
Atrial Natriuretic Factor
Thigh
atrial natriuretic factor receptor C

Keywords

  • kidney
  • lung
  • metabolism

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Physiology

Cite this

Role of natriuretic peptide clearance receptor in in vivo control of C- type natriuretic peptide. / Brandt, R. R.; Heublein, D. M.; Aarhus, L. L.; Lewicki, J. A.; Burnett, John C Jr.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 269, No. 1 38-1, 1995.

Research output: Contribution to journalArticle

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abstract = "C-type natriuretic peptide (CNP) is a newly described 22-amino acid peptide of endothelial cell origin, which has selective cardiovascular actions and is structurally related to atrial natriuretic peptide (ANP). Recent in vitro studies have demonstrated that an important regulatory pathway for the clearance of natriuretic peptides involves binding to a common clearance receptor [natriuretic peptide C receptor (NPR-C)]. Although CNP has also been identified as a ligand for NPR-C in binding assays, no studies have defined the in vivo interaction of CNP with NPR-C. CNP (10 ng · kg-1 · min-1) followed by C-ANP-(4-23), a specific ligand for NPR-C blockade, was infused intravenously in two groups (both n = 7) of anesthetized dogs at two different doses (0.1 or 1.0 μg · kg-1 · min-1) to permit calculation of total metabolic clearance rate (TMCR). C-ANP- (4-23) increased circulating CNP and reduced TMCR in both groups. Pulmonary metabolic clearance rate was negative at baseline, suggesting a net secretion of CNP across the lung, which was increased during CNP infusion and was abolished with NPR-C blockade. Renal and femoral metabolic clearance rates were positive at baseline and increased with CNP infusion. A decrease in cardiac output and cardiac filling pressures in response to CNP administration was potentiated by NPR-C blockade. We conclude that 1) circulating CNP achieved by CNP infusion is regulated by NPR-C in vivo, 2) the pulmonary circulation is a possible site of CNP secretion, 3) the renal and peripheral circulations are sites of CNP clearance, and 4) NPR-C blockade potentiates the selective cardiovascular actions of CNP.",
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