Brain natriuretic peptide is a novel cardiac hormone

doi:10.1016/S0006-291X(89)80056-7

Biochemical and Biophysical Research Communications

Volume 158, Issue 2, 31 January 1989, Pages 360-368

https://doi.org/10.1016/S0006-291X(89)80056-7 Get rights and content

Using a radioimmunoassay for brain natriuretic peptide (BNP), we have measured levels of BNP-like immunoreactivity (-LI) in extract of the porcine heart, in perfusate from the isolated porcine heart and in porcine plasma. BNP-LI was detected in the extract of the atrium, though no detectable amount of BNP-LI (more than 1 ng/g) was present in the ventricle. The BNP-LI level in the porcine atrium was 148.7 ± 23.3 ng/g. BNP-LI was also detected in the perfusate from the heart. Basal secretory rate of BNP was 3.18 ± 0.76 ng/min. Moreover, BNP-LI was detected in porcine plasma at the concentration of 4.2 ± 1.3 pg/ml. Gel filtration studies showed that BNP is present in the atrium as a large molecule and is secreted into the circulation as a small molecule. The percentage of BNP-LI to atrial natriuretic peptide (ANP)-LI was almost the same among the extract, the perfusate and the plasma (2–3 percent).

These results indicate that BNP is synthesized in and is secreted into the circulation from the heart in a similar fashion as ANP.

References (25)

MoriiN. et al.
Biochem. Biophys. Res. Commun.
(1985)
MoriiN. et al.
Biochem. Biophys. Res. Commun.
(1987)
ItohH. et al.
Brain Res. Bull.
(1986)
KatsuuraG. et al.
Eur. J. Pharmacol.
(1986)
YamadaT. et al.
Eur. J. Pharmacol.
(1986)
ItohH. et al.
Neurosci. Lett.
(1986)
ItohH. et al.
Eur. J. Pharmacol.
(1988)
KangawaK. et al.
Biochem. Biophys. Res. Commun.
(1984)
SugawaraA. et al.
Biochem. Biophys. Res. Commun.
(1985)
NakaoK. et al.
Biochem. Biophys. Res. Commun.
(1984)

SaitoY. et al.

Biochem. Biophys. Res. Commun.

(1986)

MinaminoN. et al.

Biochem. Biophys. Res. Commun.

(1988)

Cited by (220)

The natriuretic peptide system in heart failure: Diagnostic and therapeutic implications
2021, Pharmacology and Therapeutics
Citation Excerpt :
Natriuretic peptides are the most notable example of cardioprotective neurohumoral factors and consist of three family members (Nakao, Ogawa, Suga, & Imura, 1992). Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are secreted from the heart and have antagonistic actions against angiotensin II (de Bold, Bruneau, & Kuroski de Bold, 1996; Saito et al., 1989). They exhibit antagonistic effects through diuretic/natriuretic actions, vasodilatory actions, and inhibition of aldosterone secretion (Nishikimi, Maeda, & Matsuoka, 2006).
Natriuretic peptides, which are activated in heart failure, play an important cardioprotective role. The most notable of the cardioprotective natriuretic peptides are atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), which are abundantly expressed and secreted in the atrium and ventricles, respectively, and C-type natriuretic peptide (CNP), which is expressed mainly in the vasculature, central nervous system, and bone. ANP and BNP exhibit antagonistic effects against angiotensin II via diuretic/natriuretic actions, vasodilatory actions, and inhibition of aldosterone secretion, whereas CNP is involved in the regulation of vascular tone and blood pressure, among other roles. ANP and BNP are of particular interest with respect to heart failure, as their levels, most notably BNP and N-terminal proBNP—a cleavage product produced when proBNP is processed to mature BNP—are increased in patients with heart failure. Furthermore, the identification of natriuretic peptides as sensitive markers of cardiac load has driven significant research into their physiological roles in cardiovascular homeostasis and disease, as well as their potential use as both biomarkers and therapeutics. In this review, I discuss the physiological functions of the natriuretic peptide family, with a particular focus on the basic research that has led to our current understanding of its roles in maintaining cardiovascular homeostasis, and the pathophysiological implications for the onset and progression of heart failure. The clinical significance and potential of natriuretic peptides as diagnostic and/or therapeutic agents are also discussed.
Dual mode competitive electrochemical immunoassay for B-type natriuretic peptide based on GS/SnO <inf>2</inf> /polyaniline-Au and ZnCo <inf>2</inf> O <inf>4</inf> /N-CNTs
2019, Biosensors and Bioelectronics
A sensitive dual mode competitive electrochemical immunosensor for the detection of B-type natriuretic peptide (BNP) was successfully fabricated, which based on differential pulse voltammetry (DPV) and amperometric i-t curve response modes. Polyaniline (PAN) and tin dioxide (SnO₂) were loaded on graphene sheets (GS), which could effectively promote the electron transfer process, thereby amplifying the current signal and increasing the sensitivity of the immunosensor. To promote biocompatibility, gold nanoparticles (Au) were incorporated on GS/SnO₂/PAN (GS/SnO₂/PAN-Au). GS/SnO₂/PAN-Au complex was gotten to act as the platform which could provide a clearly DPV signals. N-doped carbon nanotubes (N-CNTs) embellished by ZnCo₂O₄ quantum dots (ZnCo₂O₄/N-CNTs) with excellent catalytic properties for the reduction of H₂O₂ was gotten to act as the label of the antibody-BNP (Ab), providing an obviously current signal through amperometric i-t curve method. A large quantity of BNP could be stable loaded in the modified electrode via GS/SnO₂/PAN-Au with excellent electrical conductivity and good biocompatibility, which could compete with target-BNP to combine Ab that labelled by ZnCo₂O₄/N-CNTs. Under the optimum conditions, the immunosensor exhibited remarkable analytical performance of a linear range from 0.01 pg/mL to 1 ng/mL with a detection limit of 3.4 fg/mL for quantitative detection of BNP (S/N = 3). This method was able to become a universal strategy for other biological detection.
Natriuretic peptides in human heart: Novel insight into their molecular forms, functions, and diagnostic use
2019, Peptides
Among the three natriuretic peptides, atrial/A-type natriuretic peptide (ANP) and brain/B-type natriuretic peptide (BNP) are primarily produced by, and secreted from, heart tissue. They maintain cardiovascular homeostasis by binding to natriuretic peptide receptor-A. Since plasma ANP and BNP concentrations, as well as expression, are elevated in response to increased body fluid volume and pressure load on the heart wall, these peptides are widely utilized as diagnostic biomarkers for evaluating heart failure. Regardless of their high utility, differences in their molecular forms between healthy and diseased subjects and how these relate to pathophysiology have not well been examined. Recent studies have shown that the circulating molecular forms of ANP and BNP are not uniform; bioactive α-ANP is the major ANP form, whereas the weakly active proBNP is the major BNP form. The relative ratios of the different molecular forms are altered under different pathophysiological conditions. These facts indicate that detailed measurements of each form may provide useful information on the pathophysiological state of heart tissue. Here, we revisit the relationship between the molecular forms of, and pathophysiological alterations in, human ANP and BNP and discuss the possible utility of the measurement of each of the molecular forms. The third peptide, C-type natriuretic peptide, activates natriuretic peptide receptor-B, but little is known about its production and function in the heart because of its extremely low levels. However, through recent studies, its role in the heart is gradually becoming clear. Here, we summarize its molecular forms, assay systems, and functions in the heart.
Procholecystokinin expression and processing in cardiac myocytes
2019, Peptides
The mammalian heart is by now an established endocrine organ whose myocytes in a regulated manner release atrial and ventricular natriuretic peptides (ANP and BNP). But like other hormone-producing cells in classic endocrine organs, the cardiac myocytes also express genes of additional peptide hormones. One such hormone gene is that of the well-known pleiotropic gut-brain peptide system, cholecystokinin (CCK), which is expressed at mRNA and protein levels in both atrial and ventricular cardiac myocytes. The posttranslational processing of proCCK in the myocytes, however, deviates substantially from that of other CCK-producing cells. Hence, the predominant cardiac proCCK product is devoid of the N-terminal 1–24 fragment, and besides O-sulfated at three C-terminal tyrosyl residues (Y₇₆, Y₉₀, and Y₉₂). Moreover, carboxyamidated CCK peptides are present only in very low trace amounts (≤0.1%) in comparison with the truncated and triple-sulfated proCCK fragment. The present review first summarizes present knowledge about the wide-spread expression of the CCK system in mammals, and then discusses the possible function and biomarker role of the specific cardiac proCCK variant. The review concludes that the many unsettled questions about the specific cardiac expression cascade as well as the functional and diagnostic roles of cardiac CCK are worth pursuing.
Atrial and brain natriuretic peptides: Hormones secreted from the heart
2019, Peptides
Citation Excerpt :
BNP was first identified in porcine brain tissue in 1988 by Sudoh et al. as a peptide with natriuretic-diuretic, hypotensive, and smooth muscle relaxant properties similar to those of ANP [4]. Soon thereafter, Saito et al. reported that human BNP was produced and secreted from the heart as a cardiac hormone [16]. The predominant circulating form of BNP is a 26-, 45- or 32-amino acid peptide in pig, rat and human, respectively [13].
The natriuretic peptide family consists of three biologically active peptides: atrial natriuretic peptide (ANP), brain (or B-type) natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). Among these, ANP and BNP are secreted by the heart and act as cardiac hormones. Both ANP and BNP preferentially bind to natriuretic peptide receptor-A (NPR-A or guanylyl cyslase-A) and exert similar effects through increases in intracellular cyclic guanosine monophosphate (cGMP) within target tissues. Expression and secretion of ANP and BNP are stimulated by various factors and are regulated via multiple signaling pathways. Human ANP has three molecular forms, α-ANP, β-ANP, and proANP (or γ-ANP), with proANP predominating in healthy atrial tissue. During secretion proANP is proteolytically processed by corin, resulting in secretion of bioactive α-ANP into the peripheral circulation. ProANP and β-ANP are minor forms in the circulation but are increased in patients with heart failure. The human BNP precursor proBNP is proteolytically processed to BNP_1-32 and N-terminal proBNP (NT-proBNP) within ventricular myocytes. Uncleaved proBNP as well as mature BNP_1-32 and NT-proBNP is secreted from the heart, and its secretion is increased in patients with heart failure. Mature BNP, its metabolites including BNP_3-32, BNP_4-32, and BNP_5-32, and proBNP are all detected as immunoreactive-BNP by the current BNP assay system. We recently developed an assay system that specifically detects human proBNP. Using this assay system, we observed that miR30-GALNTs-dependent O-glycosylation in the N-terminal region of proBNP contributes to regulation of the processing and secretion of proBNP from the heart.
Detection of heart failure-related biomarker in whole blood with graphene field effect transistor biosensor
2017, Biosensors and Bioelectronics
Citation Excerpt :
Studies have shown that brain natriuretic peptide (BNP) can rise in the early HF (Palazzuoli et al., 2012; Maisel et al., 2008). BNP is a cardiac hormone that is synthesized predominantly in the heart ventricles (Saito et al., 1989). It has become an internationally recognized biomarker in the diagnosis of HF (Bettencourt, 2004; de Avila et al., 2013; Rezaei et al., 2016), and has great application value and curative effect evaluation in the diagnosis and prognosis of diseases of the cardiovascular system (Mills et al., 2002; Gelfand et al., 1991).
Since brain natriuretic peptide (BNP) has become internationally recognized biomarkers in the diagnosis and prognosis of heart failure (HF), it is highly desirable to search for a novel sensing tool for detecting the patient's BNP level at the early stage. Here we report a platinum nanoparticles (PtNPs)-decorated reduced graphene oxide (rGO) field effect transistor (FET) biosensor coupled with a microfilter system for label-free and highly sensitive detection of BNP in whole blood. The PtNPs-decorated rGO FET sensor was obtained by drop-casting rGO onto the pre-fabricated FET chip and subsequently assembling PtNPs on the graphene surface. After anti-BNP was bound to the PtNPs surface, BNP was successfully detected by the anti-BNP immobilized FET biosensor. It was found that the developed FET biosensor was able to achieve a low detection limitation of 100 fM. Moreover, BNP was successfully detected in human whole blood sample treated by a custom-made microfilter, suggesting the sensor's capability of working in a complex sample matrix. The developed FET biosensor provides a new sensing platform for protein detection, showing its potential applications in clinic sample.

View all citing articles on Scopus

View full text

Brain natriuretic peptide is a novel cardiac hormone

Biochem. Biophys. Res. Commun.

Biochem. Biophys. Res. Commun.

Brain Res. Bull.

Eur. J. Pharmacol.

Eur. J. Pharmacol.

Neurosci. Lett.

Eur. J. Pharmacol.

Biochem. Biophys. Res. Commun.

Biochem. Biophys. Res. Commun.

Biochem. Biophys. Res. Commun.

Biochem. Biophys. Res. Commun.

Biochem. Biophys. Res. Commun.