B-Type Natriuretic Peptide Forms within the Heart, Coronary Sinus, and Peripheral Circulation in Humans: Evidence for Degradation before Secretion

Abstract

The B-type natriuretic peptides (BNP and N-terminal pro-BNP) are secreted by the heart and, in the case of BNP, serve to maintain circulatory homeostasis through renal and vascular actions and oppose many effects of the renin-angiotensin system. Recent evidence suggests that in patients with severe heart failure, circulating immunoreactive BNP is made up mainly of metabolites that may have reduced bioactivity. We hypothesized that BNP may be degraded before it even leaves the heart. Peripheral venous plasma plus atrial and ventricular tissue, obtained from explanted hearts at the time of transplantation, were collected from 3 patients with end-stage heart failure. In a separate study, plasma was collected from the coronary sinus and femoral artery of 3 separate patients undergoing cardiac catheterization. Plasma C18 reverse-phase extracts were separated on reverse-phase HPLC, and the collected fractions were subjected to RIAs with highly specific antisera directed to the amino- and carboxy-terminal ends of BNP(1-32). ProBNP, BNP(1-32), and 2 major BNP metabolites were present in atrial and ventricular tissue, where BNP(1-32) represented 45% and 70% of total processed BNP, respectively. Neither BNP(1-32) nor the 2 metabolites were detected in peripheral venous plasma. Nor was BNP(1-32) detected in matching coronary sinus and femoral artery plasma from the 3 patients undergoing cardiac catheterization. BNP(1-32) is partly degraded within the hearts of patients with end-stage heart failure, and even in patients with relatively well-preserved left ventricular systolic function, only BNP metabolites enter the systemic circulation.