Fortnightly Review: Ten years of natriuretic peptide research: a new dawn for their diagnostic and therapeutic use?

In 1981 de Bold et al found that atrial extracts contained a substance which caused natriuresis and vasodilatation.1 Three years later the amino acid structure of atrial natriuretic peptide was identified.2 This was followed by a period of fervent research activity to define its role and therapeutic potential. In 1988, just as the initial flush of research activity was wearing off, a second related compound was identified.3 This was called brain natriuretic peptide because it was first identified in porcine brain. It soon became clear, however, that the main source of this peptide was the cardiac ventricle rather than the brain, and brain natriuretic peptide is now sometimes called B type natriuretic peptide. In 1990 a third natriuretic peptide was identified, and in order to maintain the alphabetical nomenclature it was called C type natriuretic peptide.4 The amino acid structure of the three peptides is shown in the figure. Though C type natriuretic peptide was, like B type, initially localised to the nervous system, it was later found to be present in high concentration in the vascular tree, especially the endothelium.

The biological effects of atrial natriuretic peptide and B type natriuretic peptide are very similar, both peptides causing natriuresis, vasodilatation, and suppression of the renin-angiotensin-aldosterone system. Indeed, atrial natriuretic peptide suppresses the renin-angiotensin-aldosterone system at three separate sites. It reduces renin release, suppresses angiotensin converting enzyme activity, and blocks aldosterone release. Atrial natriuretic peptide and C type natriuretic peptide are cleared from the body by an enzyme called neutral endopeptidase and by binding to clearance receptors (see below). B type natriuretic peptide is also cleared by neutral endopeptidase, though less so by the clearance receptor mechanism. With C type natriuretic peptide the overall picture is less clear, but …