The tumultuous journey of nesiritide: past, present, and future.

Almost 3 decades ago, we witnessed the discovery of the natriuretic peptides and the role of the heart as an endocrine organ in which peptides of cardiovascular origin emerged as a humoral link between the heart and the kidney in cardiorenal homeostasis. In the United States, one such natriuretic peptide, B-type natriuretic peptide (BNP), was approved by the US Food and Drug Administration in 2001 as a drug (nesiritide) for the treatment of acute decompensated heart failure (ADHF). The rationale for the use of BNP as a cardiovascular therapy was in response to laboratorybased research and a series of clinical trials. What emerged was a theme that BNP was an endogenous ligand for the natriuretic peptide-A receptor that is linked to particulate guanylyl cyclase and the second messenger 3 ,5 -cyclic guanosine monophosphate (cGMP).1 After receptor activation, the biological actions of BNP include vasodilatation, diuresis and natriuresis, positive lusitropism, inhibition of the renin-angiotensin-aldosterone system, suppression of the myocardial hypertrophy response to pressure overload, and attenuation of myocardial fibrosis.