An initial characterization of N-terminal-proatrial natriuretic peptide in serum of Sprague Dawley rats.
In the clinical setting, natriuretic peptides (NPs) have proven to be reliable noninvasive markers for diagnostic, prognostic, and therapeutic monitoring of heart failure. Given their proven utility in humans, NPs are potential candidates for translational biomarkers during drug development to detect drug-induced hemodynamic stress resulting in cardiac hypertrophy in preclinical species. We evaluated the intra- and interassay precision and the stability of serum N-terminal-proatrial natriuretic peptide (NT-proANP) using a commercially available enzyme-linked immunoassay (EIA). We then measured NT-proANP concentrations in 532 serum samples from 337 male Crl:CD(SD) rats with or without pressure-induced cardiac hypertrophy. Additionally, we established a reference range using samples from control animals across multiple studies. The data demonstrate that the NT-proANP EIA is a robust and reproducible assay for the measurement of NT-proANP. The noninvasive translational utility, minimal sample volume requirement, and the lack of existing hypertrophic biomarkers in the male rat make NT-proANP an excellent candidate for further interrogation as a biomarker of cardiac hypertrophy in preclinical toxicology investigations.
Safety Assessment, Platform Technology & Science, Medicines Development, GlaxoSmithKline, Research Triangle Park, North Carolina 27709, USA. heidi.m.colton@gsk.com
Heidi M
HM
Colton
Alan H
AH
Stokes
Lawrence W
LW
Yoon
Michael P
MP
Quaile
Paul J
PJ
Novak
James Greg
JG
Falls
Carie L
CL
Kimbrough
Neal F
NF
Cariello
Holly L
HL
Jordan
Brian R
BR
Berridge
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002312:Cardiomyopathy, Hypertrophic / Q000097:blood*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D008297:Male; D011498:Protein Precursors / Q000097:blood*; D055550:Protein Stability; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D015415:Biomarkers; C099254:N-terminal proatrial natriuretic peptide; D011498:Protein Precursors; D009320:Atrial Natriuretic Factor