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Using a highly sensitive radioimmunoassay (RIA) system for human brain natriuretic peptide (BNP), immunoreactive (ir-) human BNP was found to be present in plasma, in addition to heart and brain tissue. Plasma concentrations of ir-BNP were 0.17-0.74 fmol/ml (mean: 0.35 fmol/ml) in normal young men, being about 1/17 of the plasma concentration of human atrial natriuretic peptide (ANP). In patients with heart disease, plasma concentration of ir-BNP increased about 100-fold (5.00-177.37 fmol/ml), being nearly comparable to that of ir-ANP, even though ANP concentration also increased about 7-fold. Two molecular forms of ir-BNP in plasma were identified as BNP-32 and gamma-BNP (pro-BNP), which are also found in cardiac atrium. In normal human plasma, gamma-BNP is the predominant molecular form, while the main form in cardiac atrium is BNP-32. These results suggest that biosynthesis and secretion of BNP are augmented in heart disease and that human BNP has a unique processing and metabolic system distinct from that of ANP.
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