The role of B-type and other natriuretic peptides in health and disease

Abstract

Natriuretic peptide (NP) physiology is a complex field. NPs also are known to be highly phylogenetically preserved. NPs can be thought of as counterregulatory hormones antagonizing the effects of the renin-angiotensin-aldosterone and sympathetic systems. These peptides are primarily responsible for maintaining salt and water homeostasis, but they also have vasodilatory properties. It was originally thought that B-type NP (BNP) and N-terminal-pro-BNP are secreted in a 1:1 ratio. However, recent data has shed further light into this area. Commercial assays for NPs will need to keep up with these changes. Currently, BNP levels within Kaiser Permanente are obtained by multiple providers in a variety of clinical scenarios in order to help them manage their patients. Therefore, a basic understanding of the physiology of NPs and the methodology of assays are needed to appropriately interpret an NP test result within the corresponding clinical scenario.

Figure 1

Schematic structure of B-type natriuretic peptide beginning at the N-terminal end and ending at the C-terminal, with amino acids 11 through 25 comprising the ring.

Figure 2

Simplistic scheme (in gray highlight). Prior model regarding B-type natriuretic peptide (BNP) release was that only two products of pro-BNP were released: BNP (active) and N-terminal-pro-BNP ([NT-pro-BNP] inactive). The current paradigm of natriuretic peptide (NP) synthesis and release consists of a variety of peptides released into bloodstream, each with varying biologic activity. NP location and release has not been fully elucidated. BNP = B-type natriuretic peptide; NT-pro-BNP = N-terminal-pro-BNP; DPP-IV = dipeptidyl peptidase–IV. Reprinted and adapted from the American Journal of Cardiology 2008 Feb 4, Supplement 1, 101(3A), Martinez-Rumayor A, Richard M, Burnett JC, Januzzi JL Jr, Biology of the natriuretic peptides, p 3–8, Copyright 2008, with permission of Elsevier. Available from: www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T10-4RR606X-5&_user=6774829&_coverDate=02%2F04%2F2008&_alid=769284664&_rdoc=1&_fmt=high&_orig=search&_cdi=4876&_docanchor=&view=c&_ct=1&_acct=C000061869&_version=1&_urlVersion=0&_userid=6774829&md5=64832291ac574f09248cd33a7f9a48cf.

Figure 3

Action of atrial natriuretic peptide (ANP) at target cells. Binding of ANP to natriuretic peptide receptor A (NPR-A) and, in an ATP-dependent fashion, stimulating the intrinsic guanylyl cyclase activity of the receptor. Cyclic guanosine monophosphate (cGMP) exerts its biologic effects. ANP binds to natriuretic peptide receptor C (NPR-C), after which it is internalized and degraded. The C-receptor may also have independent signaling functions. Finally, ANP may be degraded by the extracellular neutral endopeptidases (NEPs) in the kidney and vasculature. Reprinted with permission from Levin ER, Gardner DG, Samson WK. Natriuretic peptides. N Engl J Med 1998 Jul 30;339(5):321–8. Copyright 1998 Massachusetts Medical Society. All rights reserved.

Figure 4

Receiver-operating characteristic curve for various cutoff levels of B-type natriuretic peptide (BNP) in differentiating between dyspnea due to congestive heart failure and dyspnea due to other causes. BNP = B-type natriuretic peptide. Reprinted from Maisel AS, Krishnaswamy P, Nowak RM, et al; Breathing Not Properly Multinational Study Investigators. Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. N Engl J Med 2002 Jul 18;347(3)161–7. Copyright 2002 Massachusetts Medical Society. All rights reserved.