Brain natriuretic peptide as a novel cardiac hormone in humans. Evidence for an exquisite dual natriuretic peptide system, atrial natriuretic peptide and brain natriuretic peptide.

Mukoyama, Masashi; Nakao, Kazuwa; Hosoda, Kiminori; Suga, Shin Ichi; Saito, Yoshihiko; Ogawa, Yoshihiro; Shirakami, Gotaro; Jougasaki, Michihisa; Obata, Keisuke; Yasue, Hirofumi

doi:10.1172/jci115146

Cited by 1,263 publications

(773 citation statements)

References 51 publications

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“…ANP and BNP are secreted predominantly by the cardiac atrium and ventricle, respectively, in response to volume expansion and ventricular wall stress [9,11]. Increased cardiac secretion of BNP, as well as ANP, has been demonstrated in patients with cardiovascular diseases such as congestive heart failure, hypertension and renal failure, serving as one of the compensatory mechanisms against disease progression [11,12]. ANP and BNP share the same receptor, a particulate guanylyl cyclase (GC)-coupled receptor, or GC-A, and exert almost identical actions [13].…”

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confidence: 99%

Transgenic overexpression of brain natriuretic peptide prevents the progression of diabetic nephropathy in mice

et al. 2006

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Aims/hypothesis Brain natriuretic peptide (BNP) is a potent vasorelaxing and natriuretic peptide that is secreted from the heart and has cardioprotective properties. We have previously generated hypotensive transgenic mice (BNP-Tg mice) that overproduce BNP in the liver, which is released into the circulation. Using this animal model, we successfully demonstrated the amelioration of renal injury after renal ablation and in proliferative glomerulonephritis. Glomerular hyperfiltration is an early haemodynamic derangement, representing one of the key mechanisms of the pathogenesis of diabetic nephropathy. Based on the suggested involvement of increased endogenous natriuretic peptides, the aim of this study was to investigate their role in the development and progression of diabetic nephropathy. Materials and methods We evaluated the progression of renal injury and fibrogenesis in BNP-Tg mice with diabetes induced by streptozotocin. We also investigated the effect of BNP on high glucose-induced signalling abnormalities in mesangial cells. Results After induction of diabetes, control mice exhibited progressively increased urinary albumin excretion with impaired renal function, whereas these changes were significantly ameliorated in BNP-Tg mice. Notably, diabetic BNP-Tg mice revealed minimal mesangial fibrogenesis with virtually no glomerular hypertrophy. Glomerular upregulation of extracellular signal-regulated kinase, TGF-β and extracellular matrix proteins was also significantly inhibited in diabetic BNP-Tg mice. In cultured mesangial cells, activation of the above cascade under high glucose was abrogated by the addition of BNP. Conclusions/interpretation Chronic excess of BNP prevents glomerular injury in the setting of diabetes, suggesting that renoprotective effects of natriuretic peptides may be therapeutically applicable in preventing the progression of diabetic nephropathy.

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confidence: 99%

Transgenic overexpression of brain natriuretic peptide prevents the progression of diabetic nephropathy in mice

et al. 2006

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“…BNP is a cardiac neurohormone specifically secreted from the ventricle in response to volume expansion and pressure overload (22)(23)(24)(25). BNP is a truly ventricular hormone, and responds to changes in LV filling pressure.…”

Section: Discussionmentioning

confidence: 99%

“…Although the kinetics of atrial-derived BNP in heart failure are not fully known, some studies (23)(24)(25) propose that the atrium is the major source of secretion in the early stage of lowered cardiac function, and that BNP levels from the ventricle increase after the progression to heart failure. BNP and ANP are structurally similar, and BNP is probably also stored in secretion granules (16,33).…”

Section: Discussionmentioning

confidence: 99%

Usefulness of the brain natriuretic peptide to atrial natriuretic peptide ratio in determining the severity of mitral regurgitation

Shimamoto

Kusumoto

Sakai

et al. 2007

Canadian Journal of Cardiology

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I n chronic mitral regurgitation (MR), increased preload and reduced afterload due to unloading from the left ventricle (LV) into the left atrium (LA) leads to compensatory dilation of the LV and facilitates LV ejection. Although this response initially maintains cardiac output, myocardial decompensation eventually results in heart failure symptoms and an increased risk of sudden death. In addition, backflow into the LA results in enlargement of the LA, atrial fibrillation and elevated pulmonary pressures. In some patients, LV contractility is irreversibly impaired in the absence of symptoms (1-3). Thus, deferring surgical intervention often leads to irreversible postoperative LV dysfunction. Valve replacement or valvuloplasty is essential before the myocardial damage becomes irreversible.Early valvuloplasty conducted when heart failure is mild has been reported to improve prognosis (4). In clinical practice, however, it remains difficult to decide the timing of surgery defined by mild heart failure symptoms and preserved cardiac function.Some reports have shown that preoperative LV function (LV end-diastolic diameter [LVDd], LV end-systolic diameter BACKGROUND: Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels were characterized in subjects with mitral regurgitation (MR). METHODS: Sixty-two cases of moderate or severe chronic MR were studied. The blood levels of neurohormonal factors were stratified by the known MR prognostic factors of New York Heart Association (NYHA) functional class, left ventricular end-diastolic diameters, left ventricular end-systolic diameter (LVDs), ejection fraction (EF), left atrial diameter and presence of atrial fibrillation (AF). RESULTS: ANP levels were higher in NYHA class II and lower in classes I and III/IV (P=0.0206). BNP levels were higher in NYHA class II than class I (P=0.0355). The BNP/ANP ratio was significantly higher in NYHA classes II and III/IV than in class I (P=0.0007). To differentiate between NYHA classes I/II and III/IV, a cut-off BNP/ANP ratio of 2.97 produced a sensitivity of 78% and specificity of 87%. Compared with subjects in sinus rhythm, patients with AF had an enlarged left atrium and lower ANP levels. The BNP/ANP ratio correlated significantly with left atrial diameter, LVDs and EF (r=0.429, P=0.0017; r=0.351, P=0.0117; and r=-0.349, P=0.0122; respectively), and was significantly higher among all the known operative indications for MR tested (LVDs 45 mm or more, EF 60% or less, NYHA class II or greater and AF; P=0.0073, P=0.003, P=0.0102 and P=0.0149, respectively). CONCLUSIONS: In chronic MR, levels of ANP and BNP, and the BNP/ANP ratio are potential indicators of disease severity.

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“…In an earlier study (20) we had demonstrated that in conscious hypertensive transgenic rats with an extra renin gene (TG(m(Ren2)27)) a single administration of the NEP inhibitor ecadotril, the orally active prodrug of (S)-thiorphan, significantly increased plasma ANP levels (11). In rats with experimentally induced congestive heart failure (aortovenocaval fistula rats) acute treatment with ecadotril increased the plasma levels of endogenous ANP without having any effect in their sham-operated controls (21).…”

Section: Discussionmentioning

confidence: 99%

“…In contrast to ANP, cardiac hormone BNP is secreted predominantly from the ventricles of a hypertrophic h eart, and it is used as a marker for various stages of heart failure in humans (10). Mukoyama et al (11) have shown a higher percentage increase in plasma BNP than in plasma ANP in patients with CHF (11) and immediately after myocardial infarction (12). They also found a relationship between the plasma levels of BNP and both the degree of heart failure and that of left-ventricular dysfunction.…”

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confidence: 99%

Neutral Endopeptidase Inhibition Potentiates the Effects of Natriuretic Peptides in Renin Transgenic Rats.

1996

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The influence of neutral endopeptidase (NEP) inhibition with (S)-thiorphan on the hormonal, renal, and blood-pressure-lowering effects of an infusion of atrial (ANP), brain (BNP), and C-type natriuretic peptide (CNP) was evaluated in hypertensive transgenic rats (TGR) harboring an additional mouse renin gene (TGR(m(Ren2)27)).These TGR possess an activated natriuretic peptide system as compared with Sprague-Dawley rats (SDR), used in this study as control. (S)-Thiorphan significantly decreased blood pressure in anesthetized TGR but not in anesthetized SDR during the 60-min infusion period. Exogenously administered ANP decreased blood pressure in SDR with no significant effects in TGR after 60 min. In contrast, BNP infusion significantly decreased blood pressure in TGR, while changes in SDR were not significant. The blood pressure was further decreased after combined infusion of ANP and BNP with (S)-thiorphan in TGR. No effect on blood pressure was registered during infusion of CNP in either experimental group. The plasma levels of ANP, BNP, and cGMP were higher in TGR than in SDR, whereas plasma renin activity was lower. Co-administration of ANP, BNP, or CNP with the NEP inhibitor (S)-thiorphan potentiated the plasma ANP, BNP, and cGMP. Infusion of ANP alone did not affect BNP plasma levels of TGR and vice versa. In contrast, CNP infusion increased ANP plasma levels in both TGR and SDR. Renal excretion of sodium and cGMP increased after infusion of (S)-thiorphan and ANP or BNP in both TGR and SDR. The combination of ANP and (S)-thiorphan had a slightly greater effect on urinary excretion of sodium and cGMP in TGR than either compound alone, but the effects were more pronounced in SDR than in TGR. Finally, infusion of CNP alone and in combination with (S)-thiorphan influenced the excretion of sodium and cyclic GMP only slightly. These results indicate that inhibition of neutral endopeptidase by (S)-thiorphan potentiates the hemodynamic and renal effects of natriuretic peptides ANP and BNP, and to some extent those of CNP, in hypertensive TGR and normotensive SDR. In contrast to ANP and BNP, infusion of CNP had no effect on the blood pressure in anesthetized TGR or SDR. Inhibition of NEP therefore seems to be a promising way to potentiate endogenous levels of natriuretic peptides, which may be of therapeutic benefit in cardiovascular diseases such as hypertension or heart failure. (Hypertens Res 1996;19: 229-238) Key Words: neutral endopeptidase 24.11, (S)-thiorphan, ecadotril, TGR(m(Ren2)27), ANP, BNP, CNPThe natriuretic peptides are a family of related polypeptide hormones including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). These natriuretic peptides have a common structural motif consisting of a loop of 17 amino acids formed by intramolecular disulfide bonds. Only 6 of the 17 amino acids in this ring differ among the three peptides isolated from the pig, whereas the N-and C-terminals vary both in amino acid composition and length (1,2). Neutral m...

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Brain natriuretic peptide as a novel cardiac hormone in humans. Evidence for an exquisite dual natriuretic peptide system, atrial natriuretic peptide and brain natriuretic peptide.

Cited by 1,263 publications

References 51 publications

Transgenic overexpression of brain natriuretic peptide prevents the progression of diabetic nephropathy in mice

Transgenic overexpression of brain natriuretic peptide prevents the progression of diabetic nephropathy in mice

Usefulness of the brain natriuretic peptide to atrial natriuretic peptide ratio in determining the severity of mitral regurgitation

Neutral Endopeptidase Inhibition Potentiates the Effects of Natriuretic Peptides in Renin Transgenic Rats.

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