CD-NP: an innovative designer natriuretic peptide activator of particulate guanylyl cyclase receptors for cardiorenal disease.
The natriuretic peptide (NP) family consists of structurally similar, although physiologically distinct, peptides that play an important role in cardiorenal homeostasis. CD-NP is a novel chimeric natriuretic peptide developed by the Mayo Clinic, in which the 15-amino acid COOH-terminus of dendroaspis NP is fused to C-type NP. CD-NP is a dual activator of NP receptors A and B, and therefore, possesses the strong antiproliferative and antifibrotic properties of C-type NP with the potent natriuretic, diuretic, and aldosterone-inhibiting properties of dendroaspis NP. CD-NP has favorable cardiorenal properties when compared to recombinant B-type NP (nesiritide), including preservation of glomerular filtration rate with minimal blood pressure-lowering effects. Thus, CD-NP has emerged as an appealing novel therapeutic strategy for heart failure. The endogenous NP system, the development rationale for CD-NP, as well as in vitro, animal, and human studies and future directions will be reviewed.
McKie
Paul M
PM
Cardiorenal Research Laboratory, Division of Cardiovascular Disease, Mayo Clinic and Foundation, 200 First Street Southwest, Rochester, MN 55905, USA. mckie.paul@mayo.edu
Sangaralingham
S Jeson
SJ
Burnett
John C
JC
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D002678:Chimera; D004232:Diuretics / Q000494:pharmacology; D015195:Drug Design; D004546:Elapid Venoms / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007668:Kidney / Q000187:drug effects; D020098:Natriuretic Peptide, C-Type / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology; D050705:Receptors, Guanylate Cyclase-Coupled / Q000378:metabolism*
D000959:Antihypertensive Agents; C075597:Dendroaspis natriuretic peptide; D004232:Diuretics; D004546:Elapid Venoms; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D020098:Natriuretic Peptide, C-Type; D050705:Receptors, Guanylate Cyclase-Coupled