Plasma A- and B-type natriuretic peptides: physiology, methodology and clinical use

Time for primary review 25 days. In the 20 years which have passed since the first description by de Bold of a natriuretic and diuretic substance produced in the heart 1, a large body of research has firmly established the position of the heart as an endocrine organ. Two peptides, both containing a 17-amino acid ring structure, have been a focus of much interest: atrial natriuretic peptide (ANP), and brain (or B-type) natriuretic peptide (BNP). A third member of this family of peptides, C-type natriuretic peptide, has been described; it is mainly produced by the endothelium and not by the heart, has no diuretic or natriuretic activity, and will not be discussed here. ANP is produced mainly in the cardiac atria, while BNP, originally isolated from porcine brain, was soon reported to be mainly produced in the cardiac ventricles. In recent years, however, it has become clear that in fact both ANP and BNP are produced both in atria and in ventricles, and that ANP is normally predominant; under pathological conditions production of BNP rises strongly in both atria and ventricles and plasma concentrations may overtake those of (also risen) ANP 2, 3. Both are formed as pre-pro-polypeptides. Pro-atrial natriuretic peptide is a 126-amino acid peptide stored in atrial granulae; upon secretion it is cleaved by a serine protease into equimolar amounts of the active ANP (amino acids 99–126) and the inactive N-terminal fragment N -ANP (amino acids 1–98) 4. Further degradation of N -ANP may lead to several smaller fragments some of which may also have biological activity 5. Less is known about the procession of BNP; it is believed to be more constitutively expressed. Pro-brain natriuretic peptide is a 108-amino acid peptide also cleaved into equimolar amounts of the 32-amino acid active BNP and an … * Corresponding author. University Hospital Dijkzigt, Internal Medicine, Rm L-276, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. Tel.: +31-10-463-3764; fax: +31-10-463-4531 boomsmaatinw1. azr. nl