Plasma proANP Research Articles

The FVB mouse strain as a spontaneous model of degenerative mitral valve disease

Mitral valve disease is a complex entity with diverse origins, degeneration occurring following an extrinsic aggression (infection, autoimmune attack, drug), genetic malformation or being due to a hemodynamic abnormality (dilatation of the left ventricle, myocardial infarction). The aim is to present the main cardiovascular characteristics of the FVB mouse strain with a particular focus on spontaneous mitral valve degeneration and the serotonergic system in comparison with the C57BL/6 J, the usual background strain of many cardiovascular studies. Body weight, systolic blood pressure, heart rate, urinary 5-hydroxyindoleacetic acid (5-HIAA), whole blood and plasma serotonin, tail bleeding time, blood cell count, plasma TGF-β1 and plasma natriuretic peptide concentrations were measured in FVB/NJ and FVB/NRj mice strains (males and females) obtained from Janvier and Charles River Labs in comparison to the usual C57BL/6 background at different ages (12, 16, 20 and 24-week-old). To know if the mitral valve was remodeled, cardiac anatomy and function were assessed by echocardiography and mitral valves were finally characterized by histology. The expression of 5-HT2A and 5-HT2B receptors was measured by RTqPCR in the anterior leaflet of the valve. No significant difference in C57BL/6 J compared to FVB mice strains regarding body weight increase, arterial blood pressure and heart rate was observed. A progressive augmentation of plasma pro-ANP was observed in FVB mice. However, no cardiac hypertrophy or left-ventricular fibrosis were observed. Conversely, FVB mice demonstrated a high prevalence of fibromyxoid highly cellularized and enriched in glycosaminoglycans lesions, inducing major mitral leaflets thickening without increase in length (100% of 24-week-old FVB/NRj males). The increased thickness was correlated with urinary 5-HIAA and blood platelet count. Whole blood serotonin concentration was similar in the two strains but, in FVB, a reduction of plasma serotonin was observed together with an increase of the bleeding time. No difference regarding serotonergic receptors expression was observed. Finally, echocardiography identified left atrial and left ventricular remodeling associated with thickening of both mitral leaflets and mitral insufficient in 30% of FVB mice but no systolic protrusion of mitral leaflets towards the atrium meaning the absence of mitral valve prolapse. Spontaneous mitral myxomatous degeneration is highly prevalent in FVB mice. A contribution of the serotonergic system is suggested

Characterization of the spontaneous degenerative mitral valve disease in FVB mice.

The development of new non-surgical treatments dedicated to mitral valve degeneration is limited by the absence of relevant spontaneous and rapidly progressing animal experimental models. We characterized the spontaneous mitral valve degeneration in two inbred FVB mouse strains compared to C57BL/6J and investigated a contribution of the serotonergic system. Males and females FVB/NJ and FVB/NRj were compared to the putative C57BL/6J control at 12, 16, 20 and 24 weeks of age. Body weight, systolic blood pressure, heart rate, urinary 5-hydroxyindoleacetic acid (5-HIAA), whole blood and plasma serotonin, tail bleeding time, blood cell count, plasma TGF-β1 and plasma natriuretic peptide concentrations were measured. Myocardium and mitral valves were characterized by histology. mRNA mitral expression of 5-HT2A and 5-HT2B receptors was measured in the anterior leaflet. Cardiac anatomy and function were assessed by echocardiography. Compared to C57BL/6J, FVB mice strains did not significantly differ regarding body weight increase, arterial blood pressure and heart rate. A progressive augmentation of plasma pro-ANP was observed in FVB mice. Nevertheless, no cardiac hypertrophy or left-ventricular fibrosis were observed. Accordingly, plasma TGF-β1 was not different among the three strains. Conversely, FVB mice demonstrated a high prevalence of fibromyxoid highly cellularized and enriched in glycosaminoglycans lesions, inducing major mitral leaflets thickening without increase in length. The increased thickness was correlated with urinary 5-HIAA and blood platelet count. Whole blood serotonin concentration was similar in the two strains but, in FVB, a reduction of plasma serotonin was observed together with an increase of the bleeding time. Finally, echocardiography identified left atrial and left ventricular remodeling associated with thickening of both mitral leaflets and mitral insufficient in 30% of FVB mice but no systolic protrusion of mitral leaflets towards the atrium. The FVB mouse strain is highly prone to spontaneous mitral myxomatous degeneration. A contribution of the peripheral serotonergic system is suggested.

Atrial natriuretic peptide (ANP) as an endogenous anxiolytic in patients with heart failure? – No replication of previous results showing an inverse association of anxiety and plasma ANP parameters

ObjectiveAn acute anxiolytic-like effect of atrial natriuretic peptide (ANP) has been demonstrated in several preclinical and clinical studies. In a so far singular study (Herrmann-Lingen et al., 2003), patients with congestive heart failure, who pathognomonicly display increased plasma ANP, showed a significant inverse association of anxiety symptoms and pro-ANP levels, giving rise to speculations about ANP as an endogenous anxiolytic. We tried to replicate and extend this preliminary finding. MethodsIn 56 patients suffering from heart failure with reduced left ventricular ejection fraction we measured ANP, mid-regional pro-ANP (MR-proANP) and cyclic guanosine monophosphate (cGMP) as plasma parameters of ANP functioning and characterized anxiety symptoms using the Hospital Anxiety and Depression Scale (HADS) and in addition the State Trait Anxiety Inventory (STAI) for state anxiety. Spearman rank correlation coefficients were calculated. ResultsNone of our plasma ANP parameters showed a significant association with anxiety symptoms as per HADS ratings. The same picture emerged with STAI state anxiety. ANP, MR-proANP and cGMP significantly correlated with each other. ConclusionIn another sample of patients with heart failure we were unable to replicate previous and preliminary cross-sectional findings of low anxiety in subjects with high plasma pro-ANP. Direct measurement of effector hormone ANP and its second messenger as well did not support our hypothesis. Chronically elevated ANP in heart failure might attenuate its potential anxiolytic effects. Longitudinal studies experimentally increasing ANP levels in anxious heart failure patients are needed to test if this approach has clinical psychotropic utility.

Maternal plasma pro-atrial and C-type natriuretic peptide levels and their associations with cardiovascular and renal function in the second half of normal pregnancy: a longitudinal study

BackgroundPhysiological adaptation in pregnancy is characterized by remodeling of endocrine, cardiovascular and renal functions leading to fluid retention, volume expansion, altered cardiac loading conditions and hyperdynamic circulation. Natriuretic peptides have been used as biomarkers of cardiovascular function, but their associations with gestational age-related changes in maternal cardiac, endothelial and renal function have not been elucidated. The aim of this study was to establish longitudinal reference values for maternal plasma atrial natriuretic peptide (proANP) and C-type natriuretic peptide (CNP) and investigate their temporal association with cardiovascular and renal function in the second half of pregnancy.MethodsThis study was a prospective longitudinal study of 53 low-risk pregnancies. Women were examined every 3–5 weeks during 22–40 weeks of gestation (252 observations). Fasting maternal blood samples were obtained to measure proANP, CNP, creatinine, cystatin C, uric acid, and fibrinogen levels. Cardiac function and systemic hemodynamics were assessed noninvasively by impedance cardiography (ICG) and vascular endothelial function by flow-mediated vasodilation of brachial artery (FMD).ResultsThe plasma proANP (R2adj = 0.79; P = 0.007), CNP (R2adj = 0.54; P = 0.005) decreased between 22 and 40 weeks. The creatinine (R2adj = 0.90; P < 0.001), cystatin C (R2adj = 0.93; P = < 0.001) and uric acid (R2adj = 0.83; P < 0.001) increased significantly, whereas the estimated glomerular filtration rate (R2adj = 0.93; P < 0.001) decreased with gestational age. The FMD did not change significantly but fibrinogen (R2adj = 0.79; P < 0.001) increased with advancing gestation. The maternal systemic vascular resistance index (R2adj = 0.50; P < 0.001) increased, stroke index (R2adj = 0.62; P < 0.001) decreased, whereas the cardiac index (R2adj = 0.62; P = 0.438) and thoracic fluid content (R2adj = 0.72; P = 0.132) did not change significantly with gestation. The proANP was associated with thoracic fluid content (R2adj = 0.74; P < 0.001) and fibrinogen (R2adj = 0.78; P = 0.034) but not with other variables of systemic hemodynamics, endothelial function, or renal function. The CNP was not associated significantly with parameters of cardiovascular or renal function.ConclusionLongitudinal reference values for maternal plasma proANP and CNP were established. These natriuretic peptides decreased slightly with advancing gestation, but they did not reflect the temporal physiological changes in maternal systemic hemodynamics, vascular endothelial function and renal function during the second half of pregnancy. The proANP correlated with the thoracic fluid content reflecting volume load in pregnancy.

The central blood volume as measured by thoracic electrical impedance and plasma proANP is not compromised by donation of 900 mL of blood in men.

To evaluate whether the donation of 900 mL of blood reduces the central blood volume (CBV) assessed by thoracic electrical impedance (TI) and plasma pro-atrial natriuretic peptide (proANP). Donation of 450 mL of blood carries a 1% risk of a vasovagal reaction. Withdrawal of 900 mL of blood decreases cardiac output; however, the effect on CBV remains unknown. A randomised, single-blinded, placebo-controlled, crossover design was used, where 21 healthy semi-recumbent men donated 2 × 450 mL blood or were sham-phlebotomised. Changes in CBV were estimated by proANP and TI at 1.5 (TI1.5 ) and 100 (TI100 ) kHz, reflecting extracellular volume and (regional) total body water, respectively, and the index value (IDX; 1/T1.5 -1/TI100 ) was used to estimate changes in intracellular (red cell) volume. Systolic, diastolic and mean arterial blood pressure; heart rate; stroke volume; cardiac output; and systemic vascular resistance were monitored. After completion of the study, 1000 mL of isotonic saline was infused. Changes (mean% ± SD) in TI1.5 , TI100 and IDX were similar after 450 mL (-0.2 ± 1.6%, 0.0 ± 1.1%, -0.4 ± 10.1%) and 900 mL (0.1 ± 1.6%, 0.2 ± 1.5% and -2.0 ± 15.8%) of blood donation compared to after a sham donation of 450 mL (-0.9 ± 1.2%, -0.5 ± 1.5% and -0.1 ± 6.1%) and 900 mL (-1.2 ± 1.5%, -0.6 ± 1.3% and 0.5 ± 9.9%). In addition, changes in plasma proANP were similar after 450 and 900 mL of blood donation (-0.8 ± 6.7% and -7.6 ± 7.9%) as after sham donations (1.3 ± 7.3% and -4.5 ± 5.6%). Monitoring haemodynamic variables revealed that stroke volume decreased after the donation of 900 mL of blood (-12 ± 12 mL) compared to sham donations. During a 900-mL blood loss in semi-recumbent men, CBV measured by TI and plasma proANP is not affected.

Effect of insulin on natriuretic peptide gene expression in porcine heart

Gut hormones affect cardiac function and contractility. In this study, we examined whether insulin affects the cardiac atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) gene expression and release of proANP-derived peptides in pigs. Anaesthetized pigs were included in an experimental study comparing the effect of hyperinsulinemia in 15 pigs submitted to two different protocols versus 11 control pigs receiving saline infusion. Phosphorylation of Akt on Thr308 was determined by western blotting with a pAkt-Thr308 antibody. The mRNA contents of ANP and BNP were determined with real-time PCR; plasma and cardiac tissue proANP was measured with an immunoluminometric assay targeted against the mid-region of the propeptide and a processing-independent assay. Insulin stimulation increased phosphorylation of Akt Thr308 in both left atrium and left ventricle of porcine hearts (p < 0.005). No change was observed in ANP and BNP mRNA contents in the right or left atrium. BNP mRNA contents in the left ventricle, however, decreased 3-fold (p = 0.02) compared to control animals, whereas the BNP mRNA content in the right ventricle as well as ANP mRNA content in the right and left ventricle did not change following hyperinsulinemia. Moreover, the peptide contents did not change in the four cardiac chambers. Finally, proANP concentrations in plasma did not change during the insulin infusion compared to the control animals. These results suggest that insulin does not have direct effect on atrial natriuretic peptide expression but may have a role in the left ventricle.

Effect of early versus delayed activation of thoracic epidural anesthesia on plasma pro-atrial natriuretic peptide to indicate deviations in central blood volume during esophagectomy

Background and ObjectivesA side effect to thoracic epidural anesthesia (TEA) is hypotension induced by central hypovolemia. This study addressed whether early activation (EA) versus late activation (LA) of TEA affects...

Effect of hypotensive hypovolemia and thoracic epidural anesthesia on plasma pro-atrial natriuretic peptide to indicate deviations in central blood volume in pigs: a blinded, randomized controlled trial.

PurposeChanges in plasma pro-atrial natriuretic peptide (proANP) may indicate deviations in the central blood volume (CBV). We evaluated the plasma proANP response to hypotensive hypovolemia under the influence of thoracic epidural anesthesia (TEA) in pigs. We hypothesized that plasma proANP would decrease in response to hypotensive hypovolemia and that TEA would aggravate the proANP response, reflecting a further decrease in CBV.DesignRandomized, blinded, controlled trial.SettingA university-affiliated experimental facility.ParticipantsTwenty pigs randomized to administration of saline (placebo) or bupivacaine with morphine (TEA) in the epidural space at Th8-Th10.InterventionsRelative hypovolemia was established by an inflatable Foley catheter positioned in the inferior caval vein just below the heart (caval obstruction), and hemorrhage-induced hypovolemia was by withdrawal of blood from the femoral artery, both aiming at a mean arterial pressure (MAP) of 50–60 mmHg. Hemodynamic variables and plasma proANP were determined before and after the interventions.ResultsCaval obstruction and withdrawal of blood reduced MAP to 50–60 mmHg. Accordingly, cardiac output, central venous pressure, and mixed venous oxygen saturation decreased (p<0.05). Yet, plasma proANP was stable after both caval obstruction (TEA: 72 [63–78] to 80 pmol/L [72–85], p=0.09 and placebo: 64 [58–76] to 69 pmol/L [57–81], p=0.06) and withdrawal of blood (TEA: 74 [73–83] to 79 pmol/L [77–87], p=0.07 and placebo: 64 [56–77] to 67 pmol/L [58–78], p=0.15).ConclusionPlasma proANP was stable in response to relative and hemorrhage-induced hypovolemia to a MAP of 50–60 mmHg, and the response was independent of TEA. The findings suggest that alterations in plasma proANP do not follow deviations in CBV during hypotensive hypovolemia in pigs.

Extracellular Volume Expansion Uncovers a Natriuretic Action of Glucagon-Like Peptide-1

We have previously demonstrated that the gut hormone glucagon-like peptide-1 (GLP-1) does not affect renal hemodynamics or function at baseline conditions in healthy individuals and in patients with type 2 diabetes mellitus. However, it is possible that GLP-1 promotes renal NaCl excretion under conditions with addition of salt and water to the extracellular fluid (mimicking a mixed meal/daily NaCl load). The present study was designed to investigate whether GLP-1 induces natriuresis in healthy, volume overloaded individuals. Under fixed sodium intake, 8 healthy men were examined twice in random order during a 3-hour infusion of either GLP-1(1.5 pmol kg-1 min-1) or vehicle together with an intravenous infusion of 0.9% NaCl (750 ml/hour) given throughout both experiments. Timed urine collections were conducted throughout the experiments at voluntary voiding, and subjects remained supine during the experiments. Renal plasma flow (RPF), glomerular filtration rate (GFR), and uptake/release of hormones and ions were measured using Fick’s Principle after catheterization of a renal vein and an artery. During GLP-1 infusion, urinary sodium excretion increased compared to vehicle infusion (193 ± 40 mmol/180 min vs. 89 00B110 mmol/180 min, p&amp;lt;0.05), whereas GLP-1 had no significant effect on urine flow rate (1666 ± 284 ml/180 min vs. 1189 ± 132 ml/180 min, p=0.184). Plasma renin levels decreased similarly on both days, whereas angiotensin II levels decreased significantly only during GLP-1 infusion. During GLP-1 infusion, GLP-1 was extracted by the kidneys by about 50%. RPF and GFR remained unchanged on both days. Plasma proANP, ANP, and BNP levels remained unchanged on both days. This study shows that physiologically relevant changes in GLP-1 induce significant natriuresis independent of measurable changes in RPF and GFR in volume overloaded subjects. The natriuresis is likely brought about via a tubular mechanism secondary to suppression angiotensin II. Disclosure A. Asmar: None. P.K. Cramon: Employee; Spouse/Partner; Novo Nordisk A/S. L. Simonsen: None. M. Asmar: None. C.M. Sorensen: None. S. Madsbad: Advisory Panel; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Speaker's Bureau; Self; Eli Lilly and Company, Eli Lilly and Company. Advisory Panel; Self; Merck Sharp &amp; Dohme Corp., Sanofi-Aventis, Novo Nordisk A/S. Speaker's Bureau; Self; Novo Nordisk A/S. Research Support; Self; Novo Nordisk A/S. C. Moro: None. B. Hartmann: None. J.J. Holst: Advisory Panel; Self; Novo Nordisk A/S. Board Member; Self; Zealand Pharma A/S. Speaker's Bureau; Self; Merck Sharp &amp; Dohme Corp., AstraZeneca. Research Support; Self; Danish Diabetes Academy, Novo Nordisk Foundation. Other Relationship; Self; Antag Therapeutics. Other Relationship; Spouse/Partner; Antag Therapeutics. B.L. Jensen: None. J. Bülow: None.

Processing-independent proANP measurement for low concentrations in plasma: reference intervals and effect of body mass index and plasma glucose.

Decreased concentrations of pro-atrial-derived natriuretic peptides (proABP) in plasma have been associated with obesity and suggested as a predictor of type 2 diabetes. However, assays for measuring proANP are generally aimed to quantitate higher concentrations of proANP associated with cardiac disease. Therefore, we aimed to measure plasma proANP concentrations in a non-obese Scandinavian reference material and evaluate potential associations of plasma proANP with body mass index (BMI) and plasma glucose, respectively. We report an optimized processing-independent assay (PIA) for proANP in the lower concentration range. The assay was optimized by raising the amount of radioactive tracer and modifying the mixing ratio of resuspended plasma and buffer. Blood samples from a Scandinavian plasma cohort of 693 healthy subjects were then analyzed and age and gender-specific reference intervals were determined. Simple linear regression analyses of proANP and both BMI and plasma glucose in fasting subjects displayed insignificant associations. Multiple regression analyses supported these findings. However, a higher median plasma concentration of proANP was noted among women <50 years compared to men, whereas no gender-specific differences were seen in other age groups. Our results show that in a healthy non-obese population, BMI and plasma glucose in fasting subjects do not affect plasma proANP concentrations. Our method should be considered for future studies on low proANP concentration studies, e.g. in obesity and diabetes.

Effect of Pancreatic Hormones on pro-Atrial Natriuretic Peptide in Humans

Plasma concentrations of pro-Atrial natriuretic peptide, proANP, are decreased in obesity and diabetes. Decreased proANP concentrations have also been noted after meal intake, and recently, a glucose-mediated regulation of ANP gene expression was reported. Hence, we evaluated the effects of insulin, glucagon and glucose on plasma proANP in a series of observational and experimental studies.Six healthy men underwent seven days of bed rest. Before and after the bed rest, hyperinsulinemic euglycemic clamps with serial plasma measurements of proANP were performed. Moreover, plasma proANP was quantified in 65 individuals with normal or impaired glucose regulation. Finally, the effects of infusion-induced hyperglucagonemia were examined in ten healthy men.Bed rest decreased insulin sensitivity and plasma proANP. The decrease in proANP was not associated with insulin sensitivity and the peptide concentrations remained constant during euglycemic hyperinsulinemia and hyperglycemic hyperglucagonemia. Impaired glucose regulation was not associated with decreased proANP concentrations.Bed rest per se induces a marked decrease in plasma proANP concentrations whereas insulin resistance and impaired glucose regulation was not associated with lower proANP concentrations. Neither acute hyperinsulinemia nor hyperglucagonemia seems to affect plasma proANP. Our findings thus suggest that decreased plasma proANP concentrations occur late in the development of insulin resistance.

Plasma pro-atrial natriuretic peptide to estimate fluid balance during open and robot-assisted esophagectomy: a prospective observational study

BackgroundIt remains debated how much fluid should be administered during surgery. The atrial natriuretic peptide precursor proANP is released by atrial distension and deviations in plasma proANP are reported associated with perioperative fluid balance. We hypothesized that plasma proANP would decrease when the central blood volume is compromised during the abdominal part of robot-assisted hybrid (RE) esophagectomy and that a positive fluid balance would be required to maintain plasma proANP.MethodsPatients undergoing RE (n = 25) or open (OE; n = 25) esophagectomy for gastroesophageal cancer were included consecutively in this prospective observational study. Plasma proANP was determined repetitively during esophagectomy to allow for distinction between the abdominal and thoracic part of the procedure. The RE group was 15° head up tilted during the abdominal procedure.ResultsThe blood loss was 250 (150–375) (RE) and 600 ml (390–855) (OE) (p = 0.01), but the two groups of patients were provided with a similar positive fluid balance: 1705 (1390–1983) vs. 1528 ml (1316–1834) (p = 0.4). However, plasma proANP decreased by 21% (p < 0.01) during the abdominal part of RE carried out during moderate head-up tilt, but only by 11% (p = 0.01) during OE where the patients were supine. Plasma proANP and fluid balance were correlated in the RE-group (r = 0.5 (0.073–0.840), p = 0.02) and tended to correlate in the OE group (r = 0.4 (−0.045–0.833), p = 0.08).ConclusionThe results support that plasma proANP decreases when the central blood volume is compromised and suggest that an about 2200 ml surplus administration of crystalloid is required to maintain plasma proANP during esophagectomy.Trial registrationClinicaltrials.gov (NCT02077673). Registered retrospectively February 12th 2014.

Association between plasma proANP and hyperuricemia in Chinese Han women: a cross-sectional study.

Association between pro-atrial natriuretic peptide (proANP) and hyperuricemia has not yet been investigated in population. This study aimed to examine the association in Chinese Han women. We measured plasma proANP, serum uric acid, and other traditional biomarkers in 1360 women older than 30 years residing in the Gusu district of Suzhou City. Association between plasma proANP and hyperuricemia was analyzed in women aged ≥45 years and those aged <45 years, respectively. In women aged ≥45 years, the odds ratio (OR) [95% confidence interval (CI)] of hyperuricemia with high proANP (over the median) was 0.57 (0.34-0.97) compared to those with low proANP (p=0.040). After adjustment for age and other potential covariates, a high plasma proANP was associated with a decreased risk of hyperuricemia in women aged ≥45 years (OR 0.40; 95% CI, 0.19-0.84), when the highest and lowest categories were compared. In contrast, there was no association between plasma proANP and hyperuricemia in women aged <45 years. We did not observe a significant interaction between age and proANP (pinteraction=0.113). Sensitivity analyses further confirmed these age-specific findings. Plasma proANP was significantly and inversely associated with hyperuricemia in Chinese Han women aged ≥45 years. This study suggests that an increased plasma proANP should be a protective factor of hyperuricemia among middle-aged and old women.

Novel Chemiluminescent Enzyme Immunoassays for Individual Quantification of 3 Endogenous Molecular Forms of Atrial Natriuretic Peptide in Human Plasma.

Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) are cardiac peptide hormones with pivotal roles in maintaining cardiovascular homeostasis. BNP and its precursor fragment are accepted as gold standard markers for heart failure (HF). Human ANP is present in the atria of the heart and plasma as 3 endogenous molecular forms designated α-ANP, β-ANP, and proANP. A previous study indicated that the ratios of these 3 ANP forms are altered in the plasma of HF patients. The purpose of our study was to establish immunoassays for quantifying the individual ANP forms to collect clinical information. We developed 3 plate-based chemiluminescent enzyme immunoassays (CLEIAs) for measuring total ANP (i.e., sum of α-ANP, β-ANP, and proANP), β-ANP, and proANP levels. To minimize background signals, we added single-step PEGylation targeting the immobilized antibody in the conventional plate-based sandwich CLEIA procedure. CLEIAs with PEGylation showed sensitivity, specificity, reproducibility, and accuracy satisfying clinical requirements. Two of the CLEIAs enabled direct measurement in plasma samples. During treatments, acute decompensated HF patients exhibited marked decreases in plasma β-ANP levels but moderate decreases in plasma proANP level. The plasma ratios of α-ANP/total ANP and proANP/total ANP in acute decompensated HF patients were maintained, whereas the β-ANP/total ANP ratio was significantly decreased at discharge. The combination of the 3 CLEIAs enabled accurate quantification of α-ANP, β-ANP, and proANP, even in plasma samples, and indicated the potential of β-ANP and proANP as circulating biomarkers for HF, with different characteristics from that of BNP.

Plasma pro-atrial natriuretic peptide to indicate fluid balance during cystectomy: a prospective observational study

ObjectivesDuring surgery the volume of administered fluid is debated. Pro-atrial natriuretic peptide (proANP) is released by atrial distension, and we evaluated the relationship between changes in proANP associated with perioperative...

Using natriuretic peptides to detect cardiac diseases in horses

WHEN considering the use of cardiac biomarkers for diagnosis, prognosis and monitoring of cardiac diseases, is equine cardiology catching up with small animal and human cardiology? The paper by Van...

Total plasma proANP increases with atrial dilatation in horses

Equine atrial natriuretic peptide (ANP) plasma concentrations are correlated with left atrial size. However, species-specific assays are lacking and the results from human assays are poorly reproducible. A new methodology...

Interplay Between Adiponectin and Pro-Atrial Natriuretic Peptide and Prognosis in Patients With ST-Segment Elevation Myocardial Infarction

Natriuretic peptides (NPs) may regulate adipocyte metabolism including adiponectin. Infusion of atrial natriuretic peptide (ANP) increases plasma adiponectin in patients with heart failure. However, this relation has not been examined in a clinical setting or in myocardial infarction (MI). Accordingly, we investigated the interplay between proANP and adiponectin and the prognostic implications in patients with MI. We prospectively included 680 patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention from September 2006 to December 2008. Blood samples were drawn immediately before percutaneous coronary intervention. Additionally, we included 40 patients with 4 obtained blood samples during STEMI. Adiponectin and proANP were measured in all plasma samples. All patients were followed for 5years. End points were all-cause mortality (n= 137) and the combined end point (n=170) of major adverse cardiovascular events (MACEs). Plasma adiponectin and proANP were strongly associated at admission (r= 0.34, p <0.001). In patients with increasing proANP during STEMI, adiponectin also increased (0.5 ± 0.3 vs-0.1 ± 0.1mg/L, p= 0.026). During follow-up, patients with higher adiponectin at admission had increased risk of all-cause mortality and MACE (both, p <0.001). After adjustment for confounding risk factors by Cox regression analysis, adiponectin remained an independent predictor ofall-cause mortality and MACE: hazard ratio 1.31 (95% confidence interval 1.07 to 1.60; p= 0.009) and 1.31 (95% confidence interval 1.09 to 1.57; p= 0.004), respectively, for each SD increase. However, the association vanished when proANP was included in the analysis. In conclusion, adiponectin is associated with an increased risk of all-cause mortality and MACE. However, concomitantly elevated proANP levels appear to confound the association between adiponectin and worsened outcome.

Glucagon-like peptide-1: effect on pro-atrial natriuretic peptide in healthy males

The antihypertensive actions of glucagon-like peptide-1 (GLP1) receptor agonists have been linked to the release of atrial natriuretic peptide (ANP) in mice. Whether a GLP1–ANP axis exists in humans is unknown. In this study, we examined 12 healthy young males in a randomized, controlled, double-blinded, single-day, cross-over study to evaluate the effects of a 2-h native GLP1 infusion. Plasma proANP concentrations were measured by an automated mid-region-directed proANP immunoassay and N-terminal pro B-type natriuretic peptide (BNP) on Roche Modular E170. Urine was collected for measurements of sodium excretion. Although GLP1 infusion increased the urinary sodium excretion markedly, there were no significant changes in either proANP or proBNP concentrations. When GLP1 infusion was stopped, sodium excretion declined rapidly. As proANP concentration reflects ANP secretion, our data could not confirm the existence of a GLP1–ANP axis in humans. Especially, the natriuretic effects of GLP1 seem unlikely to be mediated exclusively via ANP.

ProANP plasma measurement predicts all-cause mortality in acutely hospitalised patients: a cohort study

ImportanceThe association of natriuretic peptide measurement with all-cause mortality in a broad selection of acutely admitted patients has not yet been examined.ObjectiveTo test the risk association between pro-atrial natriuretic peptide...