Clinical application and elucidation of significance of natriuretic peptide family

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The natriuretic peptide system consists of, at least, three endogenous ligands, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP), and three receptors, ANP receptor-A (guanylate cyclase A), ANP receptor-B (guanylate cyclase B) and clearance receptor (C receptor).ANP, the prototype of natriuretic peptides, is mainly produced in the atrium and secreted into the circulation as a cardiac hormone. ANP is also produced in the ventricle, and in the central nervous system. BNP first isolated from the porcine brain has a marked divergence in its molecular size and the sequence among species. In humans and rats, the major site of production of BNP is the ventricle of the heart. BNP is also secreted into the circulation as a cardiac hormone. The plasma BNP level in normal subjects is approximately one sixths of the plasma ANP level, however, the plasma BNP level markedly increases in heart failure, renal failure and hypertension and the augmentation of the BNP secretion is much larger than that of the ANP secretion. In addition, clearance of BNP from the circulation is slower than that of ANP. Furthermore, BNP is secreted more urgently than ANP in acute heart failure. CNP distributes mainly in the central nervous system and pituitary gland. No significant amount of CNP is detectable in the heart and plasma. Thus, CNP is a local regulator rather than a cardiac hormone.Three natriuretic receptors have ligand selectivity. The rank order in potency for cyclic GMP production via ANP receptor-A is ANP>BNP>>CNP, while that via ANP-B receptor is CNP>ANP>BNP. The rank-order of binding affinity for C receptor is ANP>CNP>BNP.The complicated natriuretic peptide system is implicated in the control of body fluid and blood pressure in endocrine and paracrine fashions.