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CD‐NP: A novel aldosterone‐suppressing designer natriuretic peptide in a first‐in‐human study
Author(s) -
Lee Candace Y.W.,
Chen Horng H.,
Lisy Ondrej,
Lieu Hsiao D.,
Burnett John C.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.757.2
Subject(s) - natriuretic peptide , aldosterone , medicine , endocrinology , agonist , receptor , chemistry , renin–angiotensin system , excretion , angiotensin ii , peptide , biochemistry , heart failure , blood pressure
Background CD‐NP is a novel chimeric natriuretic peptide (NP) consisting of the full‐length human C‐type natriuretic peptide (CNP), a NP receptor (NPR)‐B agonist, and the C‐terminus of Dendroaspis NP (DNP), a NPR‐A agonist. In the first‐in‐human clinical trial, CD‐NP activated plasma and urinary cGMP, the second messenger for the NPs, and increased Na + excretion in normal subjects. Here we report for the first time plasma aldosterone (ALDO) and angiotensin II (ANG II) levels. Methods In the double‐blind, PLB‐controlled phase of this trial, adults received CD‐NP 17.5 ng/kg/min (n = 6) or PLB (n = 4) i.v. for 4 hours. Plasma ALDO and ANG II were quantified by RIA. Data were analyzed by 2‐tailed paired t‐test and signed‐rank (S‐R) test (SAS v9). Results In subjects who received CD‐NP, plasma ALDO (mean±SD) decreased from a baseline of 21.9±2.7 to 9.5±3.2 ng/dL (P<0.001 t‐test, P<0.05 S‐R test) at the end of infusion. Plasma ANG II tended to decrease (29.2±5.2 to 23.0±3.5 ng/L, P=0.086 t‐test, P=0.69 S‐R test). In the PLB group, ALDO (20.3±4.2 to 13.6±4.5 ng/dL) and ANG II (23.3±2.2 to 19.8±8.2 ng/L) did not change. Conclusion CD‐NP suppressed plasma ALDO in normal subjects, consistent with NPR‐A activation by a novel NP with dual NPR‐A and NPR‐B activating properties. CD‐NP may be of therapeutic potential in disease states that are characterized by ALDO activation, such as in heart failure warranting further studies. Sources of funding: Mayo Foundation and Nile Therapeutics, Inc.