Atrial Natriuretic Peptide and Brain Natriuretic Peptide Coexist in the Secretory Granules of Human Cardiac Myocytes

Nakamura, Sumio; Naruse, Mitsuhide; Naruse, Kiyoko; Kawana, Masatoshi; Nishikawa, T; Hosoda, S; Tanaka, Issei; Takai, Yoshimi; Yoshihara, I; Inagami, Tadashi

doi:10.1093/ajh/4.11.909

Cited by 91 publications

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“…This observation confirms previous reports on the time course of ANP secretion in vitro 25,29,30 and is consistent with rapid depletion of a "stretch-sensitive pool" of ANP. 29 -31 ANP and BNP have been colocalized in human, 32 rat, 33 and porcine 34 cardiac myocytes, and it may be that some of the observed increases in plasma ANP, NT-proBNP, and BNP in the present study are derived from corelease from a single class of cardiac myocyte granule. Thus, it is possible that the concept of a readily releasable pool of atrial ANP for stretch-induced release 29,30 may also apply to colocalized BNP within secretory granules.…”

Section: Discussionmentioning

confidence: 54%

Deconvolution Analysis of Cardiac Natriuretic Peptides During Acute Volume Overload

et al. 2000

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Abstract-Cardiac natriuretic peptides, especially amino terminal pro-Brain Natriuretic Peptide (NT-proBNP), are emerging as powerful circulating markers of cardiac function. However, the in vivo secretion and elimination (t 1 ⁄2) of these peptides during acute volume overload have not been studied. We present the first report of the secretion and elimination of cardiac natriuretic peptides, based on deconvolution analysis of endogenous ovine plasma levels measured by specific radioimmunoassay. Four normal, conscious sheep underwent rapid right ventricular pacing (225 bpm) for 1 hour to stimulate acute cardiac natriuretic peptide release. Plasma samples and right atrial pressure measurements were taken at regular intervals 30 minutes before, during, and 4 hours after pacing. Baseline right atrial pressure significantly increased (Pϭ0.02) during the 1 hour of pacing in association with a prompt increase in plasma BNP (Pϭ0.03), atrial natriuretic peptide (Pϭ0.01), and NT-proBNP (Pϭ0.02). Deconvolution analysis showed that the t 1 ⁄2 of NT-proBNP (69.6Ϯ10.8 minutes) was 15-fold longer than BNP (4.8Ϯ1.0 minutes). Despite sustained increases in atrial pressure, cardiac secretion of natriuretic peptides (particularly atrial natriuretic peptide) fell during the pacing period, suggesting a finite source of peptide for secretion. Size-exclusion high-performance liquid chromatography revealed NT-proBNP to be a single immunoreactive peak, whereas BNP comprised at least 2 immunoreactive forms. These findings, especially the prompt secretion of BNP and the prolonged t 1 ⁄2 of NT-proBNP, clarify the metabolism of BNP forms and help to explain the diagnostic value of NT-proBNP measurement as a sensitive marker of ventricular function. Key Words: heart failure Ⅲ natriuretic peptides Ⅲ myocytes Ⅲ metabolism I ncreases in circulating volume and cardiac filling pressures promote increased secretion of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) from mammalian cardiac myocytes. ANP is synthesized and stored in the atria, whereas BNP is released from the ventricle. 1,2 ProANP is the dominant storage form in mammalian cardiac extracts 3 and is cleaved during secretion into 2 fragments, ANP [4][5][6] In contrast, myocytes contain either proBNP alone or a complex ratio of proBNP, BNP,3 suggesting that the mechanism responsible for cardiac processing of proBNP differs from that of proANP. Circulating ANP is rapidly cleared by specific clearance receptor (NPR-C) and enzymatic (neutral endopeptidase, NEP) pathways 10 -12 in contrast to 8,9,13 which is slowly metabolized and accumulates in plasma at concentrations 10-to 50-fold those of ANP. 13 Whereas BNP is cleared from the circulation by NPR-C and NEP at variable rates across species, 1,14 the absolute and proportional increment of NTproBNP in clinical and experimental heart failure 15-18 exceeds that of BNP.The growing recognition of the value of plasma levels of BNP and NT-proBNP as markers of left ventricular function 17 and prognosis after myocardial infarcti...

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Section: Discussionmentioning

confidence: 54%

Deconvolution Analysis of Cardiac Natriuretic Peptides During Acute Volume Overload

et al. 2000

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“…[11][12][13][14] Atrial natriuretic peptide (ANP) and BNP have similar properties, but the half-life of BNP is five-to six-fold longer, and BNP is mainly secreted from the ventricles in the heart, whereas ANP mainly derives from the atria. [15][16][17] There is great interest in the diagnostic use of BNP for detection of ventricular dysfunction. Several authors have suggested that determination of BNP levels could be used as a screening technique for cardiac disease.…”

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confidence: 99%

Ventricular natriuretic peptide (BNP) in heart transplantation: BNP correlation with endomyocardial biopsy, laboratory and hemodynamic measures

et al. 2003

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A prospective study of 81 heart transplant (HT) patients was carried out in order to evaluate the evolution of brain natriuretic peptide (BNP) levels in HT patients and compare them with the degree of rejection as determined by endomyocardial biopsy. All patients were subjected to endomyocardial biopsy (532), and determination of BNP and creatinine levels as well as hemodynamic parameters. A control group of 36 volunteers was included. BNP values were significantly greater in HT patients than in healthy volunteers. In the first 3 months, BNP levels in patients with treatable rejection were significantly greater than in patients without graft rejection, although evident overlapping was observed in both distributions and discriminatory potential was low. After the third month, BNP values were similar in patients with and without rejection. Creatinine levels were observed to increase over time after transplantation, but no correlation was observed between the creatinine and BNP levels. A significant positive correlation was observed between BNP and right ventricle and pulmonary arterial pressures.

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“…In contrast, the main production and secretion of BNP is from the heart ventricles (Mukoyama et al 1991), primarily the left (Yasue et al 1994), although this peptide is expressed in small amounts in the atrium. Different studies have shown that both ANP and BNP are stored in the atrium in the same granules and that both are secreted into the circulation under similar conditions (Nakamura et al 1991;Thibault et al 1992;Takemura et al 1998).…”

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confidence: 99%

Evaluation of Atrial Natriuretic Peptide and Brain Natriuretic Peptide in Atrial Granules of Rats with Experimental Congestive Heart Failure

Bialik

Abassi²,

Hammel

et al. 2001

J Histochem Cytochem.

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S U M M A R YThe natriuretic peptides are believed to play an important role in the pathophysiology of congestive heart failure (CHF). We utilized a quantitative cytomorphometric method, using double immunocytochemical labeling, to assess the characteristics of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in atrial granules in an experimental model of rats with CHF induced by aortocaval fistula. Rats with CHF were further divided into decompensated (sodium-retaining) and compensated (sodium-excreting) subgroups and compared with a sham-operated control group. A total of 947 granules in myocytes in the right atrium were analyzed, using electron microscopy and a computerized analysis system. Decompensated CHF was associated with alterations in the modal nature of granule content packing, as depicted by moving bin analysis, and in the granule density of both peptides. In control rats, the mean density of gold particles attached to both peptides was 347.0 Ϯ 103.6 and 306.3 Ϯ 89.9 gold particles/ m 2 for ANP and BNP, respectively. Similar mean density was revealed in the compensated rats (390.6 Ϯ 81.0 and 351.3 Ϯ 62.1 gold particles/ m 2 for ANP and BNP, respectively). However, in rats with decompensated CHF, a significant decrease in the mean density of gold particles was observed (141.6 Ϯ 67.3 and 158.0 Ϯ 71.2 gold particles/ m 2 for ANP and BNP, respectively; p Ͻ 0.05 compared with compensated rats, for both ANP and BNP). The ANP:BNP ratio did not differ between groups. These findings indicate that the development of decompensated CHF in rats with aortocaval fistula is associated with a marked decrease in the density of both peptides in atrial granules, as well as in alterations in the quantal nature of granule formation. The data further suggest that both peptides, ANP and BNP, may be regulated in the atrium by a common secretory mechanism in CHF.

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Atrial Natriuretic Peptide and Brain Natriuretic Peptide Coexist in the Secretory Granules of Human Cardiac Myocytes

Cited by 91 publications

References 0 publications

Deconvolution Analysis of Cardiac Natriuretic Peptides During Acute Volume Overload

Deconvolution Analysis of Cardiac Natriuretic Peptides During Acute Volume Overload

Ventricular natriuretic peptide (BNP) in heart transplantation: BNP correlation with endomyocardial biopsy, laboratory and hemodynamic measures

Evaluation of Atrial Natriuretic Peptide and Brain Natriuretic Peptide in Atrial Granules of Rats with Experimental Congestive Heart Failure

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