Atrial natriuretic factor (
ANF) is a circulating 28-amino
acid peptide that functions in the regulation of
sodium homeostasis and vascular tone.
ANF metabolism occurs via degradation by
neutral endopeptidase 24.11 and binding to the
ANF clearance receptor (ANFR-C). The present study was performed on anesthetized dogs, normal (control) and with experimental
congestive heart failure (CHF), and was designed to investigate the ability of an
ANF ligand specific for ANFR-C [
C-ANF-(4-23)] to increase plasma
ANF and also to evaluate the influence of ANFR-C on regional pulmonary and renal
ANF clearances. C-ANF-(4-23) increased plasma
ANF in controls (51 +/- 15 to 123 +/- 39 pg/ml; P < 0.05) and further increased plasma
ANF in CHF dogs (242 +/- 30 to 327 +/- 34; P < 0.05), demonstrating that ANFR-C plays a significant role in the overall metabolism and clearance of
ANF, even with chronically elevated
ANF. Infusion of C-ANF-(4-23) produced a marked decrease in
ANF pulmonary clearance (PCLANF) in controls (1,018 +/- 405 to -286 +/- 383 ml/min; P < 0.05); however, PCLANF was not altered by the
ANF ligand in CHF dogs [-137 +/- 174 to -106 +/- 226 ml/min; not significant (NS)], suggesting an occupancy of ANFR-C or a downregulation of this receptor with chronically elevated plasma
ANF.
ANF renal clearance (RCLANF) was not altered in either group by C-ANF-(4-23) infusion.(ABSTRACT TRUNCATED AT 250 WORDS)