It is 32 years since storage granules were identified in cardiac atria [1], 15 years since atrial homogenates were shown to induce a natriuresis, diuresis and a decline in arterial pressure in rat [2], and 11 years since synthetic atrial natriuretic peptide (ANP), the active 28 amino acid peptide, was demonstrated to be natriuretic, diuretic and hypotensive after intravenous injection in man [3]. We now know that ANP is released into the circulation from the atria in proportion to atrial transmural pressure, but also from the ventricles in heart failure. It serves to counteract excessive vasoconstriction and volume overload, and specifically to inhibit and counter activity of the renin–angiotensin–aldosterone system. Brain natriuretic peptide (BNP), identified only 8 years ago [4], is, despite its name, produced by the cardiac ventricles in response to stretch of ventricular myocardium [5]. Like ANP, its role under physiological circumstances and in circulatory disorders, especially congestive heart failure, appears to be as a counter-regulator to vasoconstrictor\antinatriuretic systems.

These cardiac natriuretic peptides have aroused considerable interest from several viewpoints. First, they may have therapeutic potential—not so much from their administration (as they must be given intravenously), but through inhibition of their enzymatic breakdown using drugs that inhibit neutral endopeptidase (NEP). In fact, compounds that inhibit both NEP (thereby increasing plasma ANP and possibly BNP levels) and angiotensin converting enzyme (ACE), and hence reduce angiotensin II and