Contrasting cardiac regional responses of A-type and B-type natriuretic peptide to experimental chronic heart failure

OBJECTIVE: The aim of this study was to examine the regional myocardial variation in atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) synthesis during development of congestive heart failure (CHF). METHODS: Heart failure was induced by left atrial rapid pacing for 3 weeks in pigs. The gene expression of ANP and BNP was measured by northern blot analysis and the peptide concentration in myocardial tissue and plasma by radioimmunoassay (RIA). RESULTS: At the end of the pacing period pulmonary capillary wedge pressure (PCWP) and right atrial pressure (RAP) increased, and cardiac output (CO) decreased compared to sham-operated controls (PCWP: 17.6 +/- 1.9 vs. 3.1 +/- 0.9 mmHg) (RAP: 10.4 +/- 1.7 vs. 2.2 +/- 0.6 mmHg) (CO: 3.5 +/- 0.4 vs. 5.3 +/- 0.3 l/min), indicating a state of moderate to severe CHF. The gene expression and tissue concentration of BNP was low in sham pigs, but was strongly increased in all cardiac regions, and especially in the left ventricle, during CHF. In contrast, ANP was mainly produced in the atria both in normal and heart failure conditions. The relative increases in mRNA levels, tissue concentrations and circulating peptide concentrations were more profound for BNP than for ANP. CONCLUSIONS: In response to CHF induction, ANP and BNP respond differently across the cardiac regions. Strong expression of the BNP gene was only found in the heart failure state, while ANP was clearly expressed also in the normal state. These findings support the concept of BNP being superior to ANP as a biochemical marker of CHF.