Differential regulation of cardiac ANP and BNP mRNA in different stages ofexperimental heart failure

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are ca rdiac hormones that are involved in water and electrolyte homeostasis in he art failure. Although both hormones exert almost identical biological actio ns, the differential regulation of cardiac ANP and BNP mRNA in compensated and overt heart failure is not known. To study the hypothesis that cardiac BNP is more specifically induced in overt heart failure, a large aortocaval shunt of 30 days duration was produced in rats and compared with compensat ed heart failure. Compensated heart failure was induced either by a small s hunt of 30 days duration or by a large shunt of 3 days duration. Both heart failure models were characterized by increased cardiac weight, which was s ignificantly higher in the large-shunt model, and central venous pressure. Left ventricular end-diastolic pressure was elevated only in the overt hear t failure group (control: 5.7 +/- 0.7; small shunt: 8.6 +/- 0.9; large shun t 3 days: 8.5 +/- 1.7; large shunt 30 days: 15.9 +/- 2.6 mmHg; P < 0.01). A NP and BNP plasma concentrations were elevated in both heart failure models . In compensated heart failure, ANP mRNA expression was induced in both ven tricles. In contrast, ventricular BNP mRNA expression was not upregulated i n any of the compensated heart failure models, whereas it increased in over t heart failure (left ventricle: 359 +/- 104% of control, P < 0.001; right ventricle: 237 +/- 33%, P < 0.01). A similar pattern of mRNA regulation was observed in the atria. These data indicate that, in contrast to ANP, cardi ac BNP mRNA expression might be induced specifically in overt heart failure , pointing toward the possible role of BNP as a marker of the transition fr om compensated to overt heart failure.