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2009 ; ä (191
): 341-66
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Natriuretic peptides: their structures, receptors, physiologic functions and
therapeutic applications
#MMPMID19089336
Potter LR
; Yoder AR
; Flora DR
; Antos LK
; Dickey DM
Handb Exp Pharmacol
2009[]; ä (191
): 341-66
PMID19089336
show ga
Natriuretic peptides are a family of three structurally related hormone/
paracrine factors. Atrial natriuretic peptide (ANP) and B-type natriuretic
peptide (BNP) are secreted from the cardiac atria and ventricles, respectively.
ANP signals in an endocrine and paracrine manner to decrease blood pressure and
cardiac hypertrophy. BNP acts locally to reduce ventricular fibrosis. C-type
natriuretic peptide (CNP) primarily stimulates long bone growth but likely serves
unappreciated functions as well. ANP and BNP activate the transmembrane guanylyl
cyclase, natriuretic peptide receptor-A (NPR-A). CNP activates a related cyclase,
natriuretic peptide receptor-B (NPR-B). Both receptors catalyze the synthesis of
cGMP, which mediates most known effects of natriuretic peptides. A third
natriuretic peptide receptor, natriuretic peptide receptor-C (NPR-C), clears
natriuretic peptides from the circulation through receptor-mediated
internalization and degradation. However, a signaling function for the receptor
has been suggested as well. Targeted disruptions of the genes encoding all
natriuretic peptides and their receptors have been generated in mice, which
display unique physiologies. A few mutations in these proteins have been reported
in humans. Synthetic analogs of ANP (anaritide and carperitide) and BNP
(nesiritide) have been investigated as potential therapies for the treatment of
decompensated heart failure and other diseases. Anaritide and nesiritide are
approved for use in acute decompensated heart failure, but recent studies have
cast doubt on their safety and effectiveness. New clinical trials are examining
the effect of nesiritide and novel peptides, like CD-NP, on these critical
parameters. In this review, the history, structure, function, and clinical
applications of natriuretic peptides and their receptors are discussed.