Role of the natriuretic peptide clearance receptor in the in vivo control of c-type natriuretic peptide. Brandt, Roland R., Denise M. Heublein, Lawrence L. Aarhus, John A. Lewicki, and John C. Burnett, Jr. Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Mayo Clinic and Foundation, Rochester, Minnesota 55905 and Scios Nova, Inc., Mountain View, California 94043
APStracts 2:0146H, 1995.
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. Recent in vitro studies have demonstrated that an important regulatory pathway for the clearance of natriuretic peptides involves binding to a common clearance receptor (NPR-C). While 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/min) followed by C-ANP4-23, a specific ligand for NPR-C blockade, was infused i.v. in 2 groups (both n=7) of anesthetized dogs at 2 different doses (0.1 or 1.0 [mu]g/kg/min) to permit calculation of total metabolic clearance rate (TMCR). C-ANP4-23 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, 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. 

Received 6 December 1994; accepted in final form 21 February
1995.
APS Manuscript Number H1068-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 19 April 1995.