scholarly journals N-Terminal Pro–Atrial Natriuretic Peptide Measurement in Plasma Suggests Covalent Modification

2011 ◽  
Vol 57 (9) ◽  
pp. 1327-1330 ◽  
Author(s):  
Ingrid Hunter ◽  
Urban Alehagen ◽  
Ulf Dahlström ◽  
Jens F Rehfeld ◽  
Dan L Crimmins ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Clinical Performance ◽  
Roc Curves ◽  
Healthcare Setting ◽  
Left Ventricular ◽  
Covalent Modification ◽  
Moderate Heart Failure ◽  
Atrial Natriuretic

BACKGROUND The N-terminal fragment of cardiac-derived pro–B-type natriuretic peptide is a glycosylated polypeptide. It is unknown whether N-terminal pro–atrial natriuretic peptide (proANP) fragments are also covalently modified. We therefore evaluated the clinical performance of 2 distinctly different proANP assays on clinical outcome. METHODS We examined 474 elderly patients with symptoms of heart failure presenting in a primary healthcare setting. Samples were analyzed with an automated immunoluminometric midregion proANP (MR-proANP) assay and a new processing-independent assay (PIA) developed in our laboratory. The results were compared with Bland–Altman plots, and clinical performance was assessed by generating ROC curves for different clinical outcomes. RESULTS Despite linear regression results indicating a good correlation (r = 0.85; P < 0.0001), the PIA measured considerably more proANP than the MR-proANP assay (mean difference, 663 pmol/L; SD, 478 pmol/L). In contrast, the clinical performances of the 2 assays [as assessed by the area under the ROC curve (AUC)] in detecting left ventricular dysfunction were similar [proANP PIA, 0.71 (95% CI, 0.63–0.79); MR-proANP assay, 0.74 (95% CI, 0.66–0.81); P = 0.32]. The prognostic ability to report cardiovascular mortality during a 10-year follow-up revealed AUC values of 0.66 (95% CI, 0.60–0.71) for the proANP PIA and 0.69 (95% CI, 0.63–0.74) for the MR-proANP assay (P = 0.08, for comparing the 2 assays). CONCLUSIONS Our data suggest that N-terminal proANP fragments in patient plasma differ from the calibrator peptides used but that the difference does not affect ROC curves in an elderly cohort of patients with mild to moderate heart failure. We suggest that human N-terminal proANP fragments can be covalently modified.

Role of endogenous atrial natriuretic peptide on systemic and renal hemodynamics in heart failure rats

1994 ◽  
Vol 267 (1) ◽  
pp. H182-H186 ◽  
Author(s):  
T. Nishikimi ◽  
K. Miura ◽  
N. Minamino ◽  
K. Takeuchi ◽  
T. Takeda
Keyword(s):  
Heart Failure ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Diastolic Pressure ◽  
Urinary Sodium Excretion ◽  
Left Ventricular ◽  
Renal Hemodynamics ◽  
Renal Tubular ◽  
Atrial Natriuretic

To investigate the role of endogenous atrial natriuretic peptide (ANP) in rats with heart failure (HF), we administered HS-142-1 (HS; 3 mg/kg body wt iv), a novel nonpeptide ANP-receptor antagonist, to rats with surgically induced myocardial infarction and sham-operated rats. HF was characterized by a higher left ventricular end-diastolic pressure and higher plasma ANP concentration vs. controls. HS administration significantly reduced the plasma and urinary levels of guanosine 3',5'-cyclic monophosphate in rats with HF [plasma concentration 10.6 +/- 2.6 vs. 2.7 +/- 0.4 nM (P < 0.05); urinary excretion 48 +/- 8 vs. 12 +/- 2 pmol/min (P < 0.05)]. Systemic and renal hemodynamics were unaffected by HS administration. Urine flow (-35%) and urinary sodium excretion (-50%) were significantly decreased after HS only in those rats with HF that had no changes in systemic and renal hemodynamics. These results suggest that the elevated ANP levels in HF do not contribute directly to the maintenance of systemic hemodynamics but rather compensate for the HF mainly via diuresis and natriuresis, achieved by the inhibition of renal tubular reabsorption rather than by renal vasodilatation.

Atrial natriuretic peptide and sodium homeostasis in compensated heart failure

1996 ◽  
Vol 271 (5) ◽  
pp. R1353-R1363 ◽  
Author(s):  
T. E. Lohmeier ◽  
H. L. Mizelle ◽  
G. A. Reinhart ◽  
J. P. Montani ◽  
C. E. Hord ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Output ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Plasma Levels ◽  
Left Ventricular ◽  
Sodium Balance ◽  
Plasma Norepinephrine ◽  
Norepinephrine Concentration ◽  
Atrial Natriuretic

The purpose of this study was to determine whether high plasma levels of atrial natriuretic peptide (ANP) in compensated heart failure are important in the maintenance of sodium balance. This was achieved by subjecting eight dogs to bilateral atrial appendectomy (APX) to blunt the ANP response to pacing-induced heart failure. Five intact dogs served as controls. In controls, 14 days of left ventricular pacing at 240 beats/min produced a sustained fall in cardiac output and mean arterial pressure of approximately 40 and 20%, respectively; compared with cardiac output, reductions in renal blood flow (up to approximately 25%) were less pronounced and even smaller decrements in GFR occurred (up to 9%). Despite these changes and a threefold elevation in plasma norepinephrine concentration, plasma renin activity (PRA) did not increase and sodium balance was achieved during the second week of pacing in association with a six- to eightfold rise in plasma levels of ANP. Similar responses occurred in four dogs in which APX was relatively ineffective in blunting the ANP response to pacing. In marked contrast, there were substantial increments in PRA and in plasma norepinephrine concentration, and marked sodium and water retention during the last week of pacing in four dogs with APX and severely deficient ANP. These results indicate that ANP plays a critical role in promoting sodium excretion in the early stages of cardiac dysfunction.

Atrial natriuretic peptide transcription, storage, and release in rats with myocardial infarction

1987 ◽  
Vol 253 (6) ◽  
pp. H1449-H1455 ◽  
Author(s):  
R. E. Mendez ◽  
J. M. Pfeffer ◽  
F. V. Ortola ◽  
K. D. Bloch ◽  
S. Anderson ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Chronic Heart Failure ◽  
Atrial Natriuretic Peptide ◽  
Infarct Size ◽  
Natriuretic Peptide ◽  
Left Ventricular ◽  
Coronary Artery Ligation ◽  
Mrna Levels ◽  
Atrial Natriuretic

To study the role of atrial natriuretic peptide (ANP) in chronic heart failure, ANP synthesis, storage, and release were examined by measuring atrial ANP messenger ribonucleic acid (mRNA) levels and atrial and plasma ANP concentrations in rats with myocardial infarction produced by coronary artery ligation. Three groups were defined as the following: 1) controls, sham-operated, or operated, but noninfarcted; 2) moderate infarcts, involving 5-30% of the left ventricular circumference; and 3) large infarcts (greater than or equal to 30%). In addition, to determine a possible modulation by dietary Na intake on ANP levels in heart failure, plasma immunoreactive ANP (iANP) levels were measured in rats with and without infarcts given low, regular, or high Na intake for 2 wk, by which time all groups were in neutral balance. Plasma iANP levels varied directly with increasing infarct and atrial sizes, irrespective of Na intake. In contrast, atrial ANP concentration varied inversely with increasing infarct size. The ANP mRNA content index, a measure of total atrial ANP mRNA, was significantly increased in rats with large infarcts compared with control rats. These results indicate that in rats with myocardial infarction, the severity of left ventricular dysfunction, as inferred from infarct size, but not chronic Na intake, is the primary determinant of the extent of activation of the ANP system. Elevated circulating ANP levels are maintained through enhanced atrial synthesis and release. ANP may thus play an important role in the hemodynamic and renal adaptations to chronic heart failure.

Renal hyporesponsiveness to atrial natriuretic peptide in congestive heart failure results from reduced atrial natriuretic peptide receptor concentrations

2007 ◽  
Vol 292 (5) ◽  
pp. F1636-F1644 ◽  
Author(s):  
Paula M. Bryan ◽  
Xin Xu ◽  
Deborah M. Dickey ◽  
Yingjie Chen ◽  
Lincoln R. Potter
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Guanylyl Cyclase ◽  
Left Ventricular ◽  
Natriuretic Peptide Receptor ◽  
Peptide Receptor ◽  
Protein Levels ◽  
Atrial Natriuretic

Atrial natriuretic peptide (ANP) and B-type natriuretic peptide decrease blood pressure and cardiac hypertrophy by activating natriuretic peptide receptor A (NPR-A), a transmembrane guanylyl cyclase also known as guanylyl cyclase A. Inactivation of NPR-A is a potential mechanism for the renal hyporesponsiveness observed in congestive heart failure (CHF) but direct data supporting this hypothesis are lacking. We examined whether NPR-A activity was reduced in CHF, and if so, by what mechanism. In two separate trials, CHF was induced in mice by 8-wk transverse aortic constriction. Sham controls underwent surgery without constriction. The constricted animals developed severe heart failure as indicated by increased heart weight, increased left ventricular end diastolic and systolic diameters, and decreased left ventricular ejection fractions. Kidney membranes were assayed for guanylyl cyclase activity or used to purify NPR-A by sequential immunoprecipitation/SDS-PAGE. Maximal ANP-dependent guanylyl cyclase activities were reduced by 44 or 43% in kidney membranes from CHF animals in two independent trials. Basal cyclase activities were also reduced by 31% in the second trial. The amount of phosphorylated NPR-A was reduced by 25 or 24% in kidney membranes from CHF animals as well. SYPRO Ruby staining suggested that NPR-A protein levels were similar between treatments in the first trial. However, more accurate estimates of NPR-A protein levels by immunoprecipitation/Western analysis in the second trial indicated that NPR-A protein was reduced by 30%. We conclude that reduced NPR-A protein levels, not receptor dephosphorylation, explain the renal hyporesponsiveness to natriuretic peptides in CHF.

Bovine atrial natriuretic peptide in heart failure

1990 ◽  
Vol 124 (3) ◽  
pp. 463-467 ◽  
Author(s):  
N. Takemura ◽  
H. Koyama ◽  
T. Sako ◽  
K. Ando ◽  
S. Motoyoshi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Plasma Concentration ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Right Atrium ◽  
Left Ventricular ◽  
Atrial Pressure ◽  
Right Atrial ◽  
The Right ◽  
Atrial Natriuretic

ABSTRACT 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

Abnormal rhythmic oscillations of atrial natriuretic peptide and brain natriuretic peptide in heart failure

2003 ◽  
Vol 104 (3) ◽  
pp. 303-312 ◽  
Author(s):  
Hans BENTZEN ◽  
Robert S. PEDERSEN ◽  
Henrik B. PEDERSEN ◽  
Ole NYVAD ◽  
Erling B. PEDERSEN
Keyword(s):  
Heart Failure ◽  
Atrial Natriuretic Peptide ◽  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Left Ventricular ◽  
Control Group ◽  
Pulsatile Secretion ◽  
Main Frequency ◽  
Healthy Humans ◽  
Atrial Natriuretic

The purpose of this study was to clarify whether the secretions of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are pulsatile in patients with chronic heart failure (CHF), and whether the rhythmic oscillations for ANP and BNP are abnormal in patients with CHF. Several reports have shown that ANP and especially BNP are valuable indicators of the prognosis in CHF. Previously, a pulsatile secretion has been described for ANP and BNP in healthy humans and for ANP in CHF patients. More information about the secretion pattern of BNP in heart failure is necessary to increase the clinical usefulness of BNP in patients with CHF. Patients with left ventricular systolic dysfunction and CHF (n = 12) and controls (n = 12) were investigated. Plasma ANP and BNP levels were determined every 2min during a 2-h period by radioimmunoassay and analysed for pulsatile behaviour by Fourier transformation. All patients and controls had significant rhythmic oscillations in plasma ANP levels, and 11 patients with CHF and 10 controls had significant rhythmic oscillations in plasma BNP levels. The amplitude of the main frequency was considerably higher in patients with CHF than in controls (ANP: CHF, 4.76pmol/l; controls, 0.75pmol/l; P<0.01. BNP: CHF, 3.24pmol/l; controls, 0.23pmol/l; P<0.001; all values are medians), but the main frequency did not differ significantly between the group with CHF and the control group for either ANP or BNP. Patients with CHF demonstrate pulsatile secretion of ANP and BNP with a much higher absolute amplitude, but with the same main frequency as healthy subjects.

scholarly journals Analytical performance and clinical usefulness of a commercially available IRMA kit for measuring atrial natriuretic peptide in patients with heart failure

1996 ◽  
Vol 42 (10) ◽  
pp. 1627-1633 ◽  
Author(s):  
A Clerico ◽  
G Iervasi ◽  
M G Del Chicca ◽  
S Maffei ◽  
S Berti ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Healthy Subjects ◽  
Left Ventricular ◽  
Clinical Usefulness ◽  
Left Ventricular Ejection ◽  
Plasma Samples ◽  
Patients With Heart Failure ◽  
Atrial Natriuretic

Abstract We evaluated the analytical characteristics and clinical usefulness of a commercially available IRMA kit for measuring plasma concentrations of atrial natriuretic peptide (ANP) in healthy subjects and in patients with heart failure. The method uses two monoclonal antibodies prepared against sterically remote epitopes of the ANP molecule; the first antibody is coated on the solid-phase beads, and the second is radiolabeled with 125I. Fifty-nine healthy subjects and 77 patients with heart failure were studied. After subjects had rested 20 min in a recumbent position, blood samples were collected from a brachial vein into ice-chilled disposable polypropylene tubes containing aprotinin and EDTA. Plasma samples were immediately separated by centrifugation and stored at -20 degrees C until assay. The working range (CV &lt;15%) was 10-2000 ng/L. The detection limit (2.13 +/- 0.91 ng/L) was similar to those reported for other IRMAs but was much better than those of RIAs. For healthy subjects, the results of this method (18.0 +/- 10.6 ng/L, range 4.7-63 ng/L, median 16.7 ng/L, n = 59) were similar to those generally reported for the most accurate methods, i.e., those using preliminary extraction and chromatographic purification of plasma samples. Measured plasma ANP was significantly associated with the severity of clinical symptoms, i.e., NYHA class (ANOVA, P &lt;0.0001), and with the left ventricular ejection fraction (n = 62, r = 0.618, P &lt;0.0001). Patients with severe heart failure showed greatly increased values (NYHA III-IV: 257.4 +/- 196.6 ng/L, n = 23).

Left atrial remodelling, mid-regional pro-atrial natriuretic peptide, and prognosis across a range of ejection fractions in heart failure

2020 ◽  
Author(s):  
Brendan N Putko ◽  
Anamaria Savu ◽  
Padma Kaul ◽  
Justin Ezekowitz ◽  
Jason R Dyck ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Composite Endpoint ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Lv Mass ◽  
Atrial Remodelling ◽  
Atrial Natriuretic

Abstract Aims  Measures of structural and functional remodelling of the left atrium (LA) are emerging as useful biomarkers in heart failure (HF). We hypothesized that LA volume and its contribution to stroke volume (SV) would predict a composite endpoint of HF hospitalization or death in patients with HF. Methods and results  We recruited 57 controls and 86 patients with HF, including preserved and reduced left ventricular ejection fraction (LVEF). Cardiac magnetic resonance imaging was used to evaluate LA volumes and contribution to LV SV. Plasma mid-region pro-atrial natriuretic peptide (MR-proANP) was evaluated. LA volume was negatively correlated with LVEF (P = 0.001) and positively correlated with LV mass in HFrEF (P &lt; 0.001) but not in HFpEF. LA volume at end-diastole was associated with the composite endpoint in HFrEF (hazard ratio 1.26, 95% confidence interval 1.01–1.54; P = 0.044), but not HFpEF (1.06, 0.85–1.30; P = 0.612), per 10 mL/m increase. Active contribution to SV was negatively associated with the composite endpoint in HFpEF (0.32, 0.14–0.66; P = 0.001), but not HFrEF (0.91, 0.38–2.1; P = 0.828) per 10% increase. MR-proANP was associated with the composite endpoint in HFpEF (1.46, 1.03–1.94; P = 0.034), but not in HFrEF (1.14, 0.88–1.37; P = 0.278), per 100 pM increase. Conclusion  We found different relationships between LA remodelling and biomarkers in HFrEF and HFpEF. Our results support the hypothesis that the pathophysiologic underpinnings of HFpEF and HFrEF are different, and atrial remodelling encompasses distinct components for each HF subtype.

Sign in / Sign up

Export Citation Format

Share Document