After the pivotal discovery of atrial natriuretic peptide (ANP) in 1981 and subsequent identification of BNP in 1988, the focus of worldwide research on cardiac peptides (NP) has moved over the subsequent two decades from identification and measurement to characterisation of biological actions and elucidation of the roles NP play in circulatory homeostasis, through to clinical applications. Internationally, guidelines for the diagnosis of heart failure (HF) incorporate plasma BNP/NTproBNP which assist in distinguishing HF from other diagnoses in acutely breathless patients.1 Across the spectrum of cardiovascular disease from asymptomatic risk factor through to severe HF, the B type peptides provide powerful independent prognostic information.2 3

From the mid-1980s, infusions of exogenous ANP and BNP in humans were conducted in the context of mechanistic studies aimed at determining the array and dose response of peptide bioactivity and documenting their pharmacokinetics. They confirmed a qualitatively similar array of biological actions for both ANP and BNP. They are natriuretic and diuretic. They suppress renin-angiotensin, aldosterone and sympathetic traffic.4 5 They are vasodilators. Knockout models of either peptide or their common receptor exhibit raised blood pressure and trophic changes indicating both peptides mitigate cardiac fibrosis and hypertrophy, and may have directly antiapoptotic effects.6 7

These findings gave rise to the commencement of infusions of NP in heart failure with a view to exploring the therapeutic potential of agents with what appeared to be a beneficial array of actions. The first report of B type natriuretic peptide administered to normal humans outlining the effects on haemodynamic, neuroendocrine and renal variables was published in 1990.4 Subsequently, in heart failure pathophysiological increments in plasma BNP induced by low-dose infusions of exogenous human BNP induced falls in left ventricular (LV) filling pressures in association with inhibitory effects upon renin and aldosterone …