NT-proANP Concentrations Research Articles

Endothelin-1 (ET-1), N-terminal fragment of pro-atrial natriuretic peptide (NTpro-ANP), and tumour necrosis factor alpha (TNF-α) in children with primary hypertension and hypertension of renal origin.

Hypertension is regarded as a condition of mild inflammation and endothelial imbalance. The aim of the study was to evaluate serum concentrations of biomarkers of inflammation and endothelial function: tumour necrosis factor alpha (TNF-α), endothelin-1 (ET-1), and N-terminal fragment of pro-atrial natriuretic peptide (NTpro-ANP) in hypertensive and normotensive children. We studied 63 children aged 13.56 ± 3.73 years, divided into two groups: a group with primary hypertension (n = 50) and a group with renal hypertension (n = 13). The control group consisted of 34 normotensive children aged 12.76 ± 3.96 years. Biomarkers were measured with ELISA tests. ET-1 levels were significantly higher in primary hypertension (9.93 ± 1.73 pg/ml) and renal hypertension (10.77 ± 1.50 pg/ml) in comparison to controls (4.03 ± 0.97 pg/ml), (p < 0.001, p < 0.001, respectively). NT-pro ANP concentrations in primary hypertension (71.03 ± 10.02 pg/ml), and renal hypertension (84.78 ± 6.44 pg/ml) were significantly higher than in the control group (29.62 ± 5.56 pg/ml) (p < 0.001, p < 0.001, respectively). TNF-α concentrations in primary hypertension (8.36 ± 1.60 pg/ml) and renal hypertension (7.35 ± 0.93 pg/ml) significantly exceeded concentrations in controls (4.49 ± 0.93 pg/ml), (p < 0.001, p < 0.001, respectively). ET-1 and NT-pro ANP concentrations in renal hypertension significantly exceeded those in primary hypertension (p = 0.049, p < 0.001, respectively) while TNF-α levels in renal hypertension were significantly lower than in primary hypertension (p = 0.046). The results of our study show that ET-1, NT-pro ANP, and TNF-a concentrations are increased in hypertension in children. Our investigation indicates significant importance of inflammation and endothelial involvement in hypertension in youth.

Plasma marinobufagenin immunoreactivity in patients with chronic kidney disease: a case control study.

Experimental data have shown increased plasma levels of marinobufagenin in kidney failure. In this case-controlled retrospective analysis, we evaluated plasma marinobufagenin immunoreactivity in hemodialysis patients compared with subjects with normal kidney function. Sixty-eight adult hemodialysis patients with chronic kidney disease (34 females and 34 males) as well as 68 age-, gender-, and blood pressure-matched subjects without chronic kidney disease were enrolled. Patients on stable hemodialysis regimen for at least 3 mo before the study were included. Exclusion criteria were: age <18 yr, severe liver or heart insufficiency, and overhydration. Subjects without chronic kidney disease must have had an estimated glomerular filtration rate ≥60 ml·min-1·1.72 m-2 according to the Modification of Diet in Renal Disease formula. Plasma marinobufagenin immunoreactivity was significantly ( P < 0.001) higher in hemodialysis patients (1.66 ± 1.13 nmol/l) compared with subjects with normal kidney function (0.46 ± 0.23). In hemodialysis patients, plasma marinobufagenin immunoreactivity was higher in men compared with women. A significant positive correlation has been found between plasma marinobufagenin immunoreactivity and serum NT-proBNP, NT-proANP, or aldosterone concentrations in all analyzed subjects. In hemodialyzed patients with plasma marinobufagenin immunoreactivity above median value 5-yr, all-cause mortality was higher compared with those with plasma marinobufagenin concentration below median. We have shown that plasma marinobufagenin immunoreactivity is increased in patients with end-stage kidney failure treated with hemodialysis parallel to the increase in serum NT-proBNP, NT-proANP, and aldosterone concentrations. Higher marinobufagenin immunoreactivity has been associated with worse survival in hemodialyzed patients.

Regulation of natriuretic peptides postprandially invivo and of their receptors in adipocytes by fatty acids invitro.

Natriuretic peptides (NPs) and their receptors gain attention regarding adipocyte function. It was the aim to investigate the expression of natriuretic peptide receptors NPR-A, NPR-B and NPR-C during adipocyte differentiation (AD), upon stimulation with fatty acids (FA), and in murine and human adipose tissue depots (AT) of patients undergoing bariatric surgery (n = 44). The postprandial regulation of NT-proANP and NT-proBNP levels was measured by ELISA and was studied in two cohorts of healthy individuals undergoing an oral glucose tolerance test (OGTT) (n = 100) and an oral lipid tolerance test (OLTT) (n = 100). Adipocyte mRNA expression was investigated by quantitative real-time PCR. During AD, an early expression pattern could be described for NPR-C, a bimodal expression for NPR-B and a late expression pattern for NPR-A. NPR-A and NPR-B expression was high in epididymal and subcutaneous AT but low in peri-renal AT of mice. NPR-C showed a differential expression profile. FA stimulation caused a significant and differential regulation of NPRs in adipocytes. Serum NT-proANP and NT-proBNP concentrations did not change during OGTT, whereas NT-proANP significantly declined during OLTT. Basal NT-proANP and NT-proBNP concentrations were positively correlated with each other and with FGF-19 and FGF-21 levels. Adipocytes and AT show a characteristic expression of NPRs. FA are able to regulate NPR expression differentially. There is a postprandial and negative regulation of serum NT-proANP concentrations after OLTT and of NPR-A after FA stimulation. Both effects could represent a novel hypothetical negative feedback mechanism on adipocyte lipolysis.

Evaluation of Cardiac Toxicity Biomarkers in Rats from Different Laboratories.

There is a great need for improved diagnostic and prognostic accuracy of potential cardiac toxicity in drug development. This study reports the evaluation of several commercially available biomarker kits by 3 institutions (SRI, Eli Lilly, and Pfizer) for the discrimination between myocardial degeneration/necrosis and cardiac hypertrophy as well as the assessment of the interlaboratory and interplatform variation in results. Serum concentrations of natriuretic peptides (N-terminal pro-atrial natriuretic peptide [NT-proANP] and N-terminal pro-brain natriuretic peptide [NT-proBNP]), cardiac and skeletal troponins (cTnI, cTnT, and sTnI), myosin light chain 3 (Myl3), and fatty acid binding protein 3 (FABP3) were assessed in rats treated with minoxidil (MNX) and isoproterenol (ISO). MNX caused increased heart-to-body weight ratios and prominent elevations in NT-proANP and NT-proBNP concentrations detected at 24-hr postdose without elevation in troponins, Myl3, or FABP3 and with no abnormal histopathological findings. ISO caused ventricular leukocyte infiltration, myocyte fibrosis, and necrosis with increased concentrations of the natriuretic peptides, cardiac troponins, and Myl3. These results reinforce the advantages of a multimarker strategy in elucidating the underlying cause of cardiac insult and detecting myocardial tissue damage at 24-hr posttreatment. The interlaboratory and interplatform comparison analyses also showed that the data obtained from different laboratories and platforms are highly correlated and reproducible, making these biomarkers widely applicable in preclinical studies.

Atrial natriuretic peptides in Han Wistar, Sprague–Dawley and spontaneously Hypertensive rats

The atrial natriuretic peptide (ANP) and its precursor (N-terminal fragment of atrial natriuretic peptide, NT-proANP) are natriuretic peptides released into the circulation as a consequence of an acute atrial stretch. As for the brain natriuretic peptide and its N-terminal fragment, the biological significance of ANP and NT-proANP has been widely studied in humans, but the literature is lacking information about the determination of these biomarkers in veterinary medicine and, in particular, in the toxicological species used in preclinical pharmaceutical drug development. This paper describes the evaluation of ANP and NT-proANP levels in a healthy population of Han Wistar and Sprague-Dawley rats, as well as in a rodent model of hypertension (Spontaneously Hypertensive rats). Both biomarkers were measured by mean of two commercially available enzyme immunoassays and serum levels were correlated with heart weight and histopathological findings in the heart, with the aim of building an integrated assessment of the significance of these biomarkers. Results obtained demonstrated that NT-proANP and ANP can be accurately measured in the different rat strains, with NT-proANP concentrations higher than those of ANP, as expected because of its longer half-life. In addition, both correlated well with cardiac hypertrophy evaluated by means of heart weight and histopathological examination. NT-proANP and ANP represent reliable markers of cardiac hypertrophy in the rat.

NT-proBNP, NT-proANP and cTnI concentrations in dogs with pre-capillary pulmonary hypertension

Objectives To compare [NT-proBNP], [NT-proANP] and [cTnI] between control dogs with respiratory disease without pulmonary hypertension (PH) and dogs with pre-capillary PH, and to assess the accuracy of [NT-proBNP], [NT-proANP], [cTnI] to predict Doppler-derived peak tricuspid regurgitation (TR) gradient. Animals 20 dogs. 8 control dogs with respiratory disease with no PH and 12 with pre-capillary PH. Methods [NT-proBNP], [NT-proANP] and [cTnI] were compared between the 2 groups and simple linear regression analysis was used to predict peak TR gradients from various blood biomarkers. Results Median [NT-proBNP] was higher in the dogs with PH (2011 pmol/L, 274–7713 pmol/L) compared to control dogs (744 pmol/L; 531–2710 pmol/L) ( p = 0.0339). [NT-proBNP] was associated with peak TR gradient ( R 2 = 0.7851, p = 0.0001). Median [NT-proANP] did not differ between dogs with PH (1747 fmol/L; 894–2884 fmol/L) and control dogs (1209 fmol/L; 976–1389 fmol/L ( p = 0.058). [NT-proANP] was not associated with peak TR gradient ( R 2 = 0.2780, p = 0.0781). Median [cTnI] did not differ between dogs with PH (0.2850 ng/mL; 0.19–1.13 ng/mL) and control dogs (0.2 ng/mL; 0.19–0.82 ng/mL, p = 0.3051). Median [TnI] was not associated with peak TR gradient ( R 2 = 0.024, p = 0.6307). Conclusions [NT-proBNP] concentration is significantly higher in dogs with pre-capillary PH when compared to dogs with respiratory disease without PH, and [NT-proBNP] may be useful to predict the severity of estimated PH. Elevations in [NT-proBNP] due to pre-capillary PH may complicate the interpretation of [NT-proBNP] elevations in patients presenting with cardiorespiratory abnormalities. [NT-proANP] and [cTnI] were not elevated in dogs with pre-capillary PH.

L12. The role of heparin in the prevention of preeclampsia

is associated with a significant increase in the odds of developing preeclampsia. However, these sequential changes need to be large. Cross-sectional analysis of maternal sFlt1, sEng and PlGF showmodest significant differences of at least one of these factors during the third trimester in women who develop preeclampsia in all high-risk groups. Only sFlt1 was significantly higher 2–5 weeks before the clinical onset of preeclampsia in women with previous preeclampsia. However the concentration of these circulating angiogenic factors is unlikely to be useful in predicting preeclampsia in these high-risk populations. B-type natriuretic peptide (BNP) is a 32-amino acid polypeptide that is co-secreted with the inactive amino-terminal pro B-type natriuretic peptide (NTproBNP) from the left and right cardiac ventricle in response to ventricular volume expansion and pressure overload. NT-proBNP is used in the diagnosis and followup of patients with acute and chronic heart failure. Serum concentrations of NT-proBNP may be used to monitor cardiac function during pregnancy. Tihtonen et al. has already shown as serum concentrations of NT-proBNP concentrations are significantly higher in preeclamptic women compared to chronic hypertensive and normotensive pregnancies. The author concludes that high NT-proANP and NT-proBNP concentrations in preeclampsia reflect the strain on the heart caused by high afterload. Seong et al. confirm that in patients with mild and severe preeclampsia, NTproBNP levels are elevated; Our experience gives to NTproBNP a role in predicting preeclampsia in chronic hypertensive pregnancies: this may reflect ventricular stress and/or subclinical cardiac dysfunction associated with preeclampsia.

Detection of Left Ventricular Hypertrophy in Rats Administered a Peroxisome Proliferator–Activated Receptor α/γ Dual Agonist Using Natriuretic Peptides and Imaging

Chronic treatment with suprapharmacologic doses of peroxisome proliferator-activated receptor (PPAR) agonists has a known potential for causing left ventricular hypertrophy (LVH). The mechanism by which LVH develops is not well understood nor are biomarkers of it well characterized. Natriuretic peptides are important regulators of cardiac growth, blood volume, and arterial pressure and may be useful biomarkers of LVH and hemodynamic changes that precede it. We measured amino-terminal pro-atrial natriuretic peptide (NTproANP), amino-terminal pro-brain natriuretic peptide (NTproBNP), and cardiac troponin I (cTnI) concentrations in serum and plasma, as well as transcripts in left ventricular heart tissue for atrial natriuretic peptide precursor (Nppa), brain natriuretic peptide precursor (Nppb), and myosin heavy chain-beta (Myh7) as potential biomarkers of LVH induced by a PPARalpha/gamma dual agonist in Sprague-Dawley rats. We used magnetic resonance imaging, echocardiography, and hemodynamics to identify structural and functional cardiovascular changes related to the biomarkers. Heart-to-brain weight ratios (HW:BrW) were correlated with NTproANP, NTproBNP, and cTnI concentrations in serum as well as fold change in expression of Nppa and Nppb. LVH was characterized by increased left ventricular wall thickness and inner diameter, increased cardiac output, decreased arterial blood pressure, and increased heart rate. In these studies, each end point contributed to the early detection of LVH, the ability to monitor its progression, and demonstrated the ability of NTproANP concentration in serum to predict LVH and hemodynamic changes.

Assessment of the diagnostic accuracy of circulating natriuretic peptide concentrations to distinguish between cats with cardiac and non-cardiac causes of respiratory distress

Objectives To determine if serum natriuretic peptide (NP) concentrations could distinguish cardiac from non-cardiac causes of respiratory distress (RD) in cats. Animals Seventy-four cats from 1 university hospital were used. Methods Serum NP concentrations were measured in 41 cats with non-cardiac respiratory distress (RD-NC) and compared to 33 cats with RD due to congestive heart failure (RD + CHF) using sandwich enzyme immunoassays (ELISA). Results RD-NC cats had lower ( P = 0.0001) median NT-proANP and NT-proBNP concentrations (614 and 45 fmol/mL, respectively) than RD + CHF cats (1690 and 523 fmol/mL, respectively). The area under the curve was 0.88 and 0.96 for the receiver operating curve analysis of the diagnostic accuracy of NT-proANP and NT-proBNP concentrations to discriminate RD + CHF from RD-NC cats ( P = 0.036). An optimum cut-off concentration of 986 fmol/mL for NT-proANP and 220 fmol/mL for NT-proBNP accurately discriminated RD-NC from RC + CHF cats with a sensitivity of 93.8% and 93.9% and a specificity of 80.3% and 87.8%, respectively. Conclusions Serum NP concentrations were different in RD + CHF cats compared to RD-NC cats. Evaluation of circulating NP concentrations may be helpful in the initial approach to cats presenting with respiratory distress, particularly if advances in ELISA technology result in a rapid cage-side test.

Measurement of N-terminal proatrial natriuretic peptide in plasma of cats with and without cardiomyopathy

To determine whether plasma N-terminal proatrial natriuretic peptide (Nt-proANP) concentrations in cats with cardiomyopathy (CM) differ from values in healthy cats and evaluate whether plasma Nt-proANP concentrations can be used to discriminate cats with CM and congestive heart failure (CHF) from CM-affected cats without CHF. 16 cats that had CM without CHF, 16 cats that had CM with CHF, and 11 healthy control cats. All cats underwent a physical examination, assessment of clinicopathologic variables (including plasma thyroxine concentration), thoracic radiography, and echocardiography. On the basis of findings, cats were assigned to 1 of 3 groups (control cats, cats with CM and CHF, and cats with CM without CHF). Venous blood samples were obtained from all 43 cats, and plasma Nt-proANP concentrations were measured by use of a human proANP(1-98) ELISA. Plasma Nt-proANP concentrations differed significantly among the 3 groups. Median Nt-proANP concentration was 381 fmol/mL (range, 52 to 450 fmol/mL), 763 fmol/mL (range, 167 to 2,386 fmol/mL), and 2,443 fmol/mL (range, 1,189 to 15,462 fmol/mL) in the control group, in cats with CM without CHF, and in cats with CM and CHF, respectively. Measurement of plasma Nt-proANP concentration could be of benefit in the assessment of cats with naturally occurring CM and might have potential as a screening marker for the disease. Furthermore, measurement of plasma NtproANP concentration may be useful for distinguishing cats with CM and CHF from those with CM and no CHF.

Increased fetal cardiac natriuretic peptide secretion in type‐1 diabetic pregnancies

We hypothesised that human fetal cardiac natriuretic peptide secretion is increased in type-1 diabetic pregnancies with normal placental hemodynamics, and this increase is related to the first trimester maternal glycemic control. Thirty-two neonates of type-1 diabetic mothers and 60 neonates born after uncomplicated pregnancy and labour (control group) were included in this study. Diabetic pregnancies were divided into two subgroups based on the first trimester HbA1c value. Group 1 pregnancies (n =22) had a good glycemic control (HbA1c <7.5%) and Group 2 pregnancies (n =10) had a poor glycemic control (HbA1c > or =7.5%). At delivery, an umbilical artery (UA) blood sample was obtained for assessment of N-terminal peptide of proatrial (NT-proANP) and proB-type (NT-proBNP) natriuretic peptide levels. In diabetic pregnancies, each fetus had normal UA Doppler velocimetry for gestational age. The newborn UA NT-proANP and NT-proBNP concentrations were significantly higher in type-1 diabetic pregnancies than in the control group. Group 2 fetuses with poor glycemic control showed significantly higher UA NT-proANP levels than Group 1 fetuses. UA NT-proANP levels correlated significantly with maternal HbA1c values in the first, second and third trimesters, while UA NT-proBNP levels did not correlate with maternal HbA1c values. In type-1 diabetic pregnancies, fetal cardiac natriuretic peptide secretion is increased, even in the presence of good glycemic control and normal placental hemodynamics. In addition, fetal NT-proANP levels are already related to maternal glycemic control in the first trimester of pregnancy.

Natriuretic peptides and hemodynamics in preeclampsia

The purpose of this study was to evaluate the relationship between natriuretic peptides (NT-proANP and NT-proBNP) and hemodynamic parameters in preeclampsia. This was a cross-sectional study of 19 preeclamptic, 15 chronic hypertensive, and 26 normotensive women in the third trimester of pregnancy. Stroke index (SI), heart rate (HR), cardiac index (CI), systemic vascular resistance index (SVRI), and left cardiac work index (LCWI) were derived by whole-body impedance cardiography. Systolic blood pressure (SAP), diastolic blood pressure (DAP), and mean arterial pressure (MAP) were measured. The plasma levels of NT-proANP and NT-proBNP were determined with radioimmunoassays. NT-proANP and NT-proBNP concentrations were significantly higher in preeclamptic women compared to chronic hypertensive and normotensive pregnancies. Preeclamptic women had lower CI and HR and higher SAP, MAP, and SVRI than the control groups. In preeclampsia NT-proANP correlated significantly with SAP and SVRI; meanwhile, NT-proBNP correlated significantly with SVRI and CI. These correlations persisted in the subgroup of nonmedicated preeclamptic women, except in the case of NT-proBNP and CI. High NT-proANP and NT-proBNP concentrations in preeclampsia reflect the strain on the heart caused by high afterload, rather than the function of the heart expressed as SI or CI.

Hemodynamic Adaptation during Pregnancy in Chronic Hypertension

Objective: To assess hemodynamic and NT-proANP changes in women with chronic hypertension during pregnancy. Methods: Stroke volume index (SI), heart rate (HR), cardiac output index (CI), systemic vascular resistance index (SVRI), pulse wave velocity (PWV), and left cardiac work index (LCWI) were measured using whole-body impedance cardiography. Systolic blood pressure (SAP), mean arterial pressure (MAP), diastolic blood pressure (DAP), and pulse pressure (PP) were also measured. Arterial compliance was defined as the SI-to-PP ratio (SI/PP). Hemodynamic parameters and NT-proANP concentrations were assessed during the early and late second trimester, the third trimester, and after delivery in 20 women with essential hypertension and 30 normotensive women. Results: Arterial blood pressure, SVRI, and PWV remained higher during the whole study period in chronic hypertensive compared with healthy pregnancies. In the early second trimester, women with chronic hypertension had significantly lower SI and NT-proANP concentrations than did normotensive women. Conclusion: The hemodynamics of chronic hypertension during pregnancy are characterized by persistent high vascular resistance. Lower SI and NT-proANP values found in chronic hypertensive pregnancies during the early second trimester may suggest a reduced intravascular volume increase during pregnancy.

Molecular Heterogeneity Has a Major Impact on the Measurement of Circulating N-Terminal Fragments of A- and B-Type Natriuretic Peptides

The N-terminal fragments of A- and B-type natriuretic peptides (NT-proANP and NT-proBNP) are powerful markers of cardiac function. The current assays require refinement with regard to standardization with native calibrators and the ability to detect the actual circulating forms. The following peptides were prepared with recombinant methods: NT-proANP, NT-proBNP, proBNP1-108, and Tyr0-proBNP77-108. Fifteen peptides of 13-22 amino acids, spanning the sequences of NT-proANP and NT-proBNP, were prepared by solid-phase peptide synthesis. Two immunoassays for NT-proANP and four for NT-proBNP were set up, each with a different epitope specificity. The assays were applied for the measurement of NT-proANP and NT-proBNP in healthy individuals and in patients with acute myocardial infarction. The circulating molecular forms were analyzed by gel-filtration and reversed-phase HPLC. According to the HPLC analyses, circulating NT-proANP consists mainly of the full-length peptide, with some degradation at both ends. In contrast, circulating NT-proBNP is very heterogeneous. Most immunoreactive NT-proBNP is significantly smaller in size than NT-proBNP1-76, with truncation at both termini. The smallest fragments can be detected by assays directed at the central part of NT-proBNP only; assays directed at the ends gave 30-40% lower values. Despite the difference, the various assays correlated reasonably well with each other (r2 = 0.77-0.85). In patients with acute myocardial infarction, NT-proANP and NT-proBNP concentrations were 1.8-2.3 and 4.2-4.5 times higher than in healthy individuals. The development of heart failure further increased the concentrations. Molecular heterogeneity of the circulating forms causes a serious risk of preanalytical errors in assays for NT-proBNP and, to a lesser extent, NT-proANP. The development of a sandwich assay for NT-proBNP would be especially challenging. The most robust and reliable assays use antibodies directed at the central portions of NT-proANP or NT-proBNP.

Relation of ANP and BNP to their N-terminal fragments in fetal circulation: evidence for enhanced neutral endopeptidase activity and resistance of BNP to neutral endopeptidase in the fetus.

To investigate the role of neutral endopeptidase in the turnover of atrial (ANP) and brain (BNP) natriuretic peptides and their N-terminal fragments in human fetal circulation. Retrospective case-control study. Department of Obstetrics and Gynaecology, University of Leipzig, Germany. Nine control pregnancies and nine pregnancies with rhesus isoimmunisation before and after intravascular transfusion. Natriuretic peptides and N-terminal fragments in maternal and fetal blood were measured by radio-immunoassay. Neutral endopeptidase activity was determined by HPLC. Maternal and fetal plasma concentrations of ANP, NT-proANP, BNP, NT-proBNP as well as neutral endopeptidase activity. Ratios between mature peptide and N-terminal fragment. Feto-maternal ratio. Plasma NT-proANP concentrations are 11.7 times higher in fetal than in maternal circulation. The ANP concentration is only 1.8 times higher, probably due to doubled neutral endopeptidase activity. In contrast, both NT-proBNP and BNP are doubled in fetal plasma. Fetuses with Rh isoimmunisation had significantly higher NT-proBNP but not NT-proANP and neutral endopeptidase activity than controls. An additional volume load by intravascular transfusion did not influence N-terminal fragments or neutral endopeptidase activity. Our study is the first to determine NT-pro natriuretic peptide concentrations and neutral endopeptidase activity in human fetuses. The results show that increased fetal neutral endopeptidase activity shifts the ANP/NT-proANP but not the BNP/NT-proBNP ratio and that the shifted BNP/NT-proBNP ratio in fetuses with Rh isoimmunisation does not involve increased neutral endopeptidase activity. These findings point to a BNP degradation that is not dependent on neutral endopeptidase.

NT-proANP and BNP in Renovascular and in Severe and Mild Essential Hypertension

Background/Aims: The plasma concentrations of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) become increased in hypertension. However, it is unknown what is the effect of the etiology and the severity of hypertension on the plasma concentrations of ANP and BNP. Methods: We examined plasma levels of ANP (measured as N-terminal fragment of proatrial natriuretic peptide; NT-proANP) and BNP in patients having sustained hypertension of different etiology and severity: in patients with renovascular hypertension (RVHT, n = 12), severe essential hypertension (SEHT, n = 37), and mild essential hypertension (MEHT, n = 29). In addition, we studied the diagnostic value of NT-proANP and BNP to discriminate patients with RVHT from patients with essential hypertension. Results: The plasma concentrations of NT-proANP and BNP were higher in the RVHT group (593 ± 80 and 25.0 ± 9.3 pmol/l, respectively) than in the SEHT group (320 ± 33 and 4.7 + 0.6 pmol/l, respectively; p < 0.001 for both), in spite of the similar blood pressure level, and also higher than in the MEHT group (356 ± 30 and 7.0 ± 1.0 pmol/l; p = 0.004 and p = 0.006, respectively). There was no difference in natriuretic peptide levels between the SEHT and MEHT groups. Plasma NT-proANP and BNP correlated positively with aging and serum creatinine concentration and inversely with left ventricular diastolic filling. In addition, NT-proANP correlated positively with systolic blood pressure and BNP with left ventricular mass index. The areas under receiver operating characteristic curves for plasma NT-proANP and BNP to discriminate RVHT patients from patients with essential hypertension were 0.793 and 0.782, respectively. The best cutoff value was 530 pmol/l for NT-proANP, giving a sensitivity of 67% with a specificity of 86%. The cutoff value of 9.8 pmol/l for BNP resulted in a sensitivity of 58% and a specificity of 90%. Conclusions: Patients with RVHT have higher plasma levels of NT-proANP and BNP than patients with essential hypertension. In addition to the etiology of hypertension, also left ventricular characteristics are important determinants of NT-proANP and BNP concentrations in hypertension. Due to the low sensitivity, NT-proANP and BNP are not suitable as screening tools for RVHT.

Effects of dilated cardiomyopathy on the renin-angiotensin-aldosterone system, atrial natriuretic peptide activity, and thyroid hormone concentrations in dogs.

To evaluate the effect of dilated cardiomyopathy (DCM) on activity of the renin-angiotensin-aldosterone system (RAAS), the N-terminal fragment of proatrial natriuretic peptide (NT-proANP), and thyroid hormone concentrations in dogs. 15 dogs with clinical signs of DCM, 15 dogs without clinical signs of DCM, and 15 age-, breed-, and sex-matched control dogs. Physical examinations, thoracic radiography, ECG, and echocardiography were performed on all dogs, and blood and urine samples were collected. Plasma renin activity (PRA), plasma aldosterone concentration (PAC), urine aldosterone-to-creatinine ratio, and NT-proANP concentrations were significantly increased in dogs with clinical signs of DCM, compared with dogs without clinical signs and control dogs. Thyroid-stimulating hormone and total thyroxine concentrations did not differ significantly among groups; however, free thyroxine (FT4) concentrations were significantly decreased in dogs with clinical signs of DCM, compared with control dogs and DCM-dogs without clinical signs. Concentrations of PRA, PAC, FT4, and urine aldosterone-to-creatinine ratio were significantly correlated, whereas plasma concentrations of NT-proANP only correlated with FT4 concentration. In dogs with clinical signs of DCM, increased concentrations of components of the RAAS were associated with increased concentrations of NT-proANP Analysis of the neurohormonal system may aid in identification of clinical stages of DCM for groups of dogs, but the range is too great and there are too many dogs that have neurohormonal concentrations within reference ranges to assess dogs on an individual basis.

Differential responses of plasma atrial and brain natriuretic peptides to acute alteration in atrial pressure in pigs

To describe the differential dynamic responses of atrial natriuretic peptide (ANP), N-terminal proatrial natriuretic peptide (Nt-proANP) and brain natriuretic peptide (BNP) to acute changes in atrial pressure, 6 pigs were studied during and after a 24-h period of rapid atrial pacing (225 bpm). During pacing, left atrial pressure increased acutely. ANP plasma concentrations showed a sharp initial peak followed by a decline, but remained significantly increased throughout the 24-h period. Nt-proANP followed a smoother pattern, increasing significantly only after 24 h. BNP increased significantly after 8 h after pacing and even more after 24 h. An opposite but similarly differential pattern of peptide responses was found in the post-pacing period. The different responses in ANP, Nt-proANP and BNP plasma concentrations may reflect the different mechanisms of regulation of secretion as well as plasma clearance. If the present findings reflect the acute clinical situation in humans, they may be of diagnostic relevance. An isolated ANP elevation would indicate a recent acute pressure increase, while elevation of two or more natriuretic peptides would point to a pressure increase of longer duration.

Hormonal responses and cardiac filling pressures in head-up or head-down position and pneumoperitoneum in patients undergoing operative laparoscopy

In order to determine if there are differences in stress responses, as reflected in neuroendocrine activation, we have compared data from two groups of patients undergoing laparoscopic surgery either in the head-up position for cholecystectomy or in the head-down position for hysterectomy. Arterial blood samples were obtained for measurement of serum concentrations of cortisol, catecholamines, renin activity and atrial natriuretic peptide (measured as N-terminal peptide of proANP), and haemodynamic data (pulmonary capillary wedge pressure, PCWP) were collected at the following times: in awake patients, supine at rest (baseline); in awake patients in the position used during surgery; during laparoscopy; and 2 h after surgery. The same anaesthetic technique and normocapnic mechanical ventilation were used in both groups. There were no significant differences between groups in cortisol or adrenaline concentrations, or in renin activity. There was, however, a three-fold increase in cortisol towards the recovery period in both groups. Noradrenaline concentrations increased more in the head-up group suggesting increased sympathetic nervous activity. In awake patients, plasma NT-proANP concentrations were significantly higher in the head-down tilt compared with the head-up position, and NT-proANP correlated well with PCWP. During pneumoperitoneum, however, NT-proANP concentrations remained low in spite of increased PCWP suggesting that inflation of the abdomen interferes with venous return. In conclusion, abdominal surgical laparoscopy in both the head-up and head-down positions caused marked activation of neuroendocrine responses. The two surgical positions, however, differed in their effect on the circulation. In awake patients, head-down tilt was associated with increased concentrations of plasma NT-proANP, indicating increased venous return and atrial stretch.

Plasma N-terminal atrial natriuretic peptide in acute myocardial infarction

Plasma atrial natriuretic peptide (ANP) and the N-terminal (NT) fragment of the 126-amino acid prohormone of ANP (proANP; NT-proANP) were correlated with clinical findings in 41 patients with acute myocardial infarction and in 19 patients with angina pectoris. On admission to the hospital, the 39 patients with nonfatal infarction who subsequently had overt heart failure ( n = 8) had plasma NT-proANP (2374 ± 1038 pmol/L) and ANP (54 ± 43 pmol/L) concentrations that were higher ( p < 0.01) than those in the patients who remained without or who presented with minor signs of failure. In contrast to the relatively stable NT-proANP levels, ANP decreased markedly during the first 24 hours in the patients who had any signs of failure. Hence the plasma levels of NT-proANP and ANP did not go hand in hand in acute myocardial infarction, and NT-proANP appeared to be a better marker of cardiac dysfunction than ANP.