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Cathy A Guo and Shaodong Guo

Introduction Insulin resistance is the major underlying mechanism for metabolic and cardiovascular dysfunction in obesity and type 2 diabetes mellitus (T2D) ( Qi 2016 ). T2D is a high-risk factor in promoting heart failure and its prevalence

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Ricardo Rodríguez-Calvo, Josefa Girona, Josep M Alegret, Alba Bosquet, Daiana Ibarretxe and Lluís Masana

Introduction Heart failure (HF) is one of the most important health problems around the world (for a review, see Hunt et al . 2009 ). The prevalence of HF is especially ominous in developed societies. Between the EU and the United States

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Sushil K Mahata, Hong Zheng, Sumana Mahata, Xuefei Liu and Kaushik P Patel

Introduction Enhanced neurohumoral drive is a major risk factor that influences the progression of chronic heart failure (HF) and mortality in patients and the experimental models ( Packer 1988 , Zucker et al . 1995 , Patel 1997 ). During

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Vanesa Jiménez-Amilburu, Susanne Jong-Raadsen, Jeroen Bakkers, Herman P Spaink and Rubén Marín-Juez

Introduction Cardiovascular pathologies are a leading cause of mortality ( Pagidipati & Gaziano 2013 ). Heart failure constitutes the primary cause of death in developed countries and its occurrence increases rapidly in developing countries ( Sliwa

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N. Takemura, H. Koyama, T. Sako, K. Ando, S. Motoyoshi and F. Marumo


The present study describes the concentration and molecular form of atrial natriuretic peptide (ANP) in Holstein dairy cattle with mild (bacterial endocarditis; BEC) or severe (dilated cardiomyopathy; DCM) heart failure. Significant increases in plasma concentration of ANP were observed in cattle with DCM (73·3 ± 16·02 pmol/l, n=4, P<0·01) and BEC (20·6± 3·45 pmol/l, n=7, P<0·05), when compared with those in control cattle (14·5± 1·84 pmol/l, n= 12). The concentration of ANP in cattle with DCM was significantly (P<0·01) higher compared with that in cattle with BEC. Plasma concentration of ANP correlated significantly with right atrial pressure (r =0·95, P<0·01) and left ventricular end-diastolic pressure (r= 0·84, P<0·01). Gel-permeation chromatography of ANP in plasma and the right atrium from control and cattle with BEC revealed a single peak corresponding to the elution position of authentic human ANP(99–126) in plasma, and two peaks corresponding to those of authentic human ANP(99–126) and pro-ANP in the atrial extract. In cattle with DCM, however, peaks corresponding to the elution positions of authentic human β-ANP and/or pro-ANP were detected in addition to the peak corresponding to ANP(99–126). The content of ANP in the right atrium of cattle with DCM was significantly (P<0·05) increased compared with that in control cattle and those with BEC. The present study therefore suggests that the synthesis and secretion of ANP might be stimulated by atrial distention induced by increased atrial pressure. This suggestion is supported by the fact that the middle molecular weight form of ANP, possibly corresponding to human β-ANP, was detected in both the plasma and atria of the cattle with severe heart failure.

Journal of Endocrinology (1990) 124, 463–467

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Jarrad M Scarlett, Darren D Bowe, Xinxia Zhu, Ayesha K Batra, Wilmon F Grant and Daniel L Marks

Introduction Chronic heart failure (CHF) is a major public health problem in western countries, with an incidence approaching 10 per 1000 population per year in those aged 65 years or older ( Cowie et al . 1999 , Lloyd-Jones et al . 2002 ). In

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N Hirayama, K Kitamura, T Imamura, J Kato, Y Koiwaya, T Tsuji, K Kangawa and T Eto

In the biosynthesis of adrenomedullin (AM), an intermediate form, AM(1-52)-glycine-COOH (iAM), is cleaved from proAM and subsequently processed to a biologically active mature form, AM(1-52)-NH2 (mAM), by enzymatic amidation. We recently reported that immunoreactive AM in human plasma consists of mAM and iAM. To clarify the pathophysiological roles of mAM and iAM in heart failure, we established an assay method to specifically detect mAM, and we determined the plasma concentrations of mAM and iAM in 68 patients with congestive heart failure (CHF). The plasma mAM concentrations of the CHF patients classified as being class I or II of New York Heart Association (NYHA) functional classification were significantly greater than those of the 28 healthy controls, and a further increase was noted in the class III or IV patients. Similar increases in plasma iAM were also observed in these patients compared with controls. The increased plasma mAM and iAM in 12 patients with exacerbated CHF were significantly reduced by treatment of their CHF for 7 days. In addition, the plasma concentrations of both mAM and iAM were significantly correlated with pulmonary capillary wedge pressure, pulmonary artery pressure, right atrial pressure, cardiothoracic ratio, heart rate, and the plasma concentrations of atrial and brain natriuretic peptides in the CHF patients. Thus the plasma concentrations of both mAM and iAM were increased progressively in proportion to the severity of CHF. These results suggest that, though the role of iAM remains to be clarified, mAM acts against the further deterioration of heart failure in patients with CHF.

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C Azizi, G Maistre, H Kalotka, R Isnard, C Barthélemy, F Masson, P Pham, F Pousset, J Eurin, P Lechat, M Komajda and A Carayon


A specific and sensitive radioimmunoassay (RIA) for the N-terminal fragment of proatrial natriuretic peptide (NproANP) was developed. Antiserum raised in rabbits against a mixture enriched with prohormone was 100% cross-reactive with human proANP(1–30). Plasma concentrations of proANP(1–30) and ANP immunoreactivities (ir-) were simultaneously measured in healthy subjects and patients with congestive heart failure (CHF; 26 dilated cardiomyopathy and 5 ischemic heart disease). High plasma levels of both ir-proANP(1–30) and ir-ANP were detected in CHF patients. Circulating ir-ANP levels were elevated in New York Heart Association functional Classes II and III patients but not in Class I patients. However, plasma levels of ir-proANP(1–30) were higher in asymptomatic patients than in healthy subjects, and markedly increased in patients of Classes II and III. Analysis of ir-proANP(1–30) by gel filtration chromatography or reverse-phase high pressure liquid chromatography revealed a 10 kDa peptide circulating as a distinct entity.

These findings indicate that: (i) the most probable form of NproANP in human plasma is a 10 kDa peptide and (ii) in CHF patients the rise in plasma ir-proANP(1–30) levels is more pronounced than the variation in plasma ir-ANP. Thus, NproANP plasma levels may prove to be a more sensitive marker of left ventricular dysfunction than ANP.

Journal of Endocrinology (1996) 148, 51–57

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CJ Pemberton, TG Yandle, CJ Charles, MT Rademaker, GD Aitken and EA Espiner

Whereas numerous studies have examined the cardiac tissue content and secretion of atrial natriuretic peptide (ANP), the response of brain natriuretic peptide (BNP) in states of experimental cardiac overload is less well documented. Our recent partial cloning of the ovine BNP gene has enabled us to study changes in cardiac tissue concentration, together with tissue and circulating molecular forms of ANP and BNP, in response to cardiac overload induced by rapid ventricular pacing (n = 7) and aortic coarctation (n = 6). In normal sheep, although highest levels of BNP were found in atrial tissue (15-fold those of the ventricle), the BNP/ANP concentration ratio in the ventricles was 10- to 20-fold higher than the ratio calculated for atrial tissue. Compared with normal sheep, significant depletion of both ANP and BNP concentrations within the left ventricle occurred after rapid ventricular pacing. Size exclusion and reverse phase HPLC analysis of atrial and ventricular tissue extracts from normal and overloaded sheep showed a single peak of high molecular weight BNP consistent with the proBNP hormone. In contrast, immunoreactive BNP extracted from plasma drawn from the coronary sinus was all low molecular weight material. Further analysis of plasma BNP using ion exchange HPLC disclosed at least 3 distinct immunoreactive peaks consistent with ovine BNP forms 26-29 amino acid residues in length. These findings show that BNP is stored as the prohormone in sheep cardiac tissues and that complete processing to mature forms occurs at the time of secretion. The capacity to process the prohormone at secretion is not impaired by chronic heart failure.

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Sung Wook Park, Shawna D Persaud, Stanislas Ogokeh, Tatyana A Meyers, DeWayne Townsend and Li-Na Wei

heart failure ( Nichtova et al. 2012 , Garg & Khanna 2014 ). β-Adrenergic stimulation activates cAMP-protein kinase A (PKA) signaling and CaMKII ( Grimm & Brown 2010 ) through multiple mechanisms. Initial activation of CaMKII by Ca 2+ /calmodulin