title: Atrial natriuretic peptides in Han Wistar, Sprague-Dawley and spontaneously hypertensive rats.
abstract: The atrial natriuretic peptide (ANP) and its precursor (N-terminal fragment of atrial natriuretic peptide, NT-proANP) are natriuretic peptides released into the circulation as a consequence of an acute atrial stretch. As for the brain natriuretic peptide and its N-terminal fragment, the biological significance of ANP and NT-proANP has been widely studied in humans, but the literature is lacking information about the determination of these biomarkers in veterinary medicine and, in particular, in the toxicological species used in preclinical pharmaceutical drug development. This paper describes the evaluation of ANP and NT-proANP levels in a healthy population of Han Wistar and Sprague-Dawley rats, as well as in a rodent model of hypertension (Spontaneously Hypertensive rats). Both biomarkers were measured by mean of two commercially available enzyme immunoassays and serum levels were correlated with heart weight and histopathological findings in the heart, with the aim of building an integrated assessment of the significance of these biomarkers. Results obtained demonstrated that NT-proANP and ANP can be accurately measured in the different rat strains, with NT-proANP concentrations higher than those of ANP, as expected because of its longer half-life. In addition, both correlated well with cardiac hypertrophy evaluated by means of heart weight and histopathological examination. NT-proANP and ANP represent reliable markers of cardiac hypertrophy in the rat.
authors.affiliation: Safety Assessment Department, GlaxoSmithKline Research Centre, Verona, Italy. patrizia.g.cristofori@gsk.com
authors.forename: Federica
authors.initials: F
authors.lastname: Crivellente
authors.forename: Nicola
authors.initials: N
authors.lastname: Bocchini
authors.forename: Monica
authors.initials: M
authors.lastname: Bonato
authors.forename: Luca
authors.initials: L
authors.lastname: Vandin
authors.forename: Ivo
authors.initials: I
authors.lastname: Faustinelli
authors.forename: Patrizia
authors.initials: P
authors.lastname: Cristofori
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D001794:Blood Pressure; D006332:Cardiomegaly / Q000097:blood; D006207:Half-Life; D006325:Heart Atria / Q000378:metabolism; D008297:Male; D009929:Organ Size; D011863:Radioimmunoassay; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar
chemical_list: D015415:Biomarkers; D009320:Atrial Natriuretic Factor