DIFFERENTIAL ATRIAL AND VENTRICULAR EXPRESSION OF MYOCARDIAL BNP DURING EVOLUTION OF HEART-FAILURE

Although brain natriuretic peptide (BNP) of myocardial origin is impor tant in cardiovascular and renal function and as a marker of cardiac d ysfunction, the expression of BNP in atrial and ventricular myocardium remains controversial both under normal conditions and in heart failu re. We therefore determined left atrial and left ventricular (LV) gene expression and tissue concentration as well as circulating BNP during the evolution of rapid ventricular pacing-induced congestive heart fa ilure (CHF) in the dog. Early LV dysfunction after 10 days of pacing w as characterized by impaired LV function but maintained arterial press ure, and overt CHF after 38 days of pacing was characterized by furthe r impaired LV function and decreased systemic arterial pressure. Under normal conditions, cardiac BNP mRNA and cardiac tissue BNP were of at rial origin. In early LV dysfunction, BNP mRNA and tissue BNP were mar kedly increased in the left atrium in association with an increase in circulating BNP but remained below or at the limit of detection in the LV. In overt CHF, BNP mRNA was further increased in the left atrium a nd first increased in the LV, together with an increase in LV tissue B NP and a further increase in circulating BNP. In the progression of CH F, early LV dysfunction is characterized by a selective increase in at rial BNP expression in association with increased circulating BNP. Ove rt CHF is characterized by an additional recruitment of ventricular BN P expression and a further increase in circulating BNP. These studies provide important new insight into the local and temporal regulation o f cardiac BNP gene expression during the progression of heart failure and underscore the predominant endocrine role of atrial myocardium und er normal conditions and in early LV dysfunction.