The mature form of brain natriuretic peptide (BNP) is formed from the BNP (1-108) precursor and is secreted predominantly by the cardiac ventricles. Circulating forms of BNP include BNP-32 (77-108), a high molecular weight BNP which has not been well characterized and and the nt-proBNP (1-76). The BNP fragment is typically measured as a proxy for BNP because of its longer half-life. Recent research suggests that natriuretic peptides are important protectors against fluid overload and high blood pressure. BNP has also been implicated as a valuable marker in assessing cardiac risk.
The natriuretic peptides are members of a family of structurally similar but genetically distinct peptide hormones, consisting of atrial-, brain-, and C-type (ANP, BNP, and CNP, respectively). ANP and BNP preferentially bind to a membrane-bound guanylyl cyclase (GC) receptor called GC-A or NPR1, whereas CNP is the physiological ligand for GC-B (NPR2). The natriuretic peptides play an important role in the regulation of cardiovascular and renal homeostasis and in the regulation of fatty acid metabolism and body weight.
BNP is mainly expressed by ventricular myocardium in response to volume overload and increased filling pressure. BNP has a cleavable signal sequence. Mature BNP consists of 108 amino acids (proBNP or BNP-108), and undergoes cleavage resulting in physiologically active BNP-32 and additional C-terminal fragments along with a physiologically inactive N-terminal peptide comprising amino acids 1-76, which is further degraded proteolytically. BNP fragments in the circulation are therefore very heterogenous.
BNP has a key role in cardiovascular homeostasis with biological actions including natriuresis, diuresis, vasorelaxation, and inhibition of renin and aldosterone secretion. A high concentration of BNP in the bloodstream is indicative of heart failure. The discovery of natriuretic peptides identified an endocrine system that contributes to diuresis and vascular tone. The biology, biochemistry and the pathophysiological role of natriuretic peptides are described in several reviews.
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