This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Burnett, J. C. Articles by Korinek, J. Search for Related Content PubMed PubMed Citation Articles by Burnett, J. C., Jr Articles by Korinek, J. Related Collections Cardio-renal physiology/pathophysiology

Editorials

The Tumultuous Journey of Nesiritide

Past, Present, and Future

John C. Burnett, Jr, MD and Josef Korinek, MD

From the Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minn.

Correspondence to John C. Burnett, Jr, MD, Mayo Clinic and Foundation, 200 First St SW, Rochester, MN 55905. E-mail burnett.john@mayo.edu

Key Words: Editorials • heart failure • natriuretic peptides

An extract of the first 250 words of the full text is provided, because this article has no abstract.

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 laboratory-based 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.

Article p 9

Although a hallmark of acute and chronic congestive heart failure (CHF) is an increased plasma level of BNP, there are functional derangements in the BNP/cGMP signaling pathway that provide additional rationale for the exogenous administration of BNP or nesiritide to treat CHF. The 2 most compelling abnormalities include increased production of less biologically active BNP forms and increased renal resistance to BNP in severe experimental CHF.^2–5

Since the initial report in 1991 by Yoshimura et al⁶ and after several clinical trials . . . [Full Text of this Article]

This article has been cited by other articles:

				C. Y. W. Lee, H. H. Chen, O. Lisy, S. Swan, C. Cannon, H. D. Lieu, and J. C. Burnett Jr. Pharmacodynamics of a Novel Designer Natriuretic Peptide, CD-NP, in a First-in-Human Clinical Trial in Healthy Subjects J. Clin. Pharmacol., June 1, 2009; 49(6): 668 - 673. [Abstract] [Full Text] [PDF]