IntroductionBrain and atrial natriuretic peptides (BNP and ANP) are cardiac hormones with diuretic, natriuretic, and vasodilatory activities. Cardiomyopathic hamsters are widely used animal models of heart failure. Due to the structural divergence of BNP among species, examination on pathophysiological roles of BNP using cardiomyopathic hamsters is so far impossible. We therefore isolated hamster BNP and ANP cDNAs, and investigated synthesis and secretion of these peptides in normal and cardiomyopathic hamsters. The COOH-terminal 32-residue peptide of cloned hamster preproBNP with 122 amino acids, preceded by a single arginine residue, supposedly represents hamster BNP showing < 50% homology to rat BNP. Alpha-hamster ANP, 28-residue peptide, is identical to a-rat ANP. In hamsters, BNP and ANP occur mainly in the ventricle and the atrium, respectively. The 32-wk-old hypertrophic cardiomyopathic B1014.6 strain exhibited ventricular hypertrophy. The 32-wk-old dilated cardiomyopathic B1053.58 strain remained at the stage without apparent heart failure. In B1014.6 and B1053.58 strains at this age, ventricular BNP and ANP gene expressions are augmented, and the plasma BNP concentration is elevated to 136 and 108 fmol/ml, respectively, three times greater than the elevated plasma ANP concentration, which well mimics changes of the plasma BNP and ANP concentrations in human heart failure. Cardiomyopathic hamsters, therefore, are useful models to investigate the implication of BNP in human cardiovascular diseases. (J. Clin. Invest. 1994. 94:1059-1068 Key words: cardiac hypertrophy -congestive heart failure * gene expression * radioimmunoassay * tissue distribution Address correspondence to Kazuwa Nakao, Second Division, Department of Medicine, Kyoto University Faculty of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606, Japan.Received for publication 6 December 1993 and in revised form 4 May 1994.1. Abbreviations used in this paper: AMI, acute myocardial infarction; ANP, atrial natriuretic peptide; BNP, brain natriuretic peptide; CHF, congestive heart failure; CNP, C-type natriuretic peptide; DOCA, deoxycorticosterone acetate; HOCM, hypertrophic obstructive cardiomyopathy; HP-GPC, high-performance gel permeation chromatography; LI, like immunoreactivity; SHR, spontaneously hypertensive rats.Since the discovery of atrial natriuretic peptide (ANP)' in the heart (1), it has been demonstrated that ANP is synthesized in and secreted from the heart, implicated in body fluid homeostasis and blood pressure control as a cardiac hormone (2). In normal hearts, ANP is produced mainly in the atrium and only slightly occurs in the ventricle, whereas in patients with congestive heart failure (CHF) and animal models of ventricular hypertrophy, ANP synthesis and secretion are greatly augmented in the ventricle (3-6).Brain natriuretic peptide (BNP), a second natriuretic peptide, was originally isolated from the porcine brain (7). This peptide shows a sequence homology to ANP (7) and has peripheral and central actions similar to t...