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Sample records for pro b-type natriuretic

  1. Clinical implications of B-type natriuretic peptide and N-terminal pro--B-type natriuretic peptide in the care of the vascular surgery patient.

    PubMed

    Wayne Causey, Marlin; Singh, Niten

    2014-12-01

    B-type natriuretic peptide (also known as brain natriuretic peptide or BNP) is a physiologic marker that is often used to assess a patient's global cardiovascular health. BNP is secreted from the ventricular cardiac myocytes in response to stretch that occurs due to increased intravascular volume. PreproBNP is cleaved into BNP and N-terminal proBNP (NT proBNP) to cause diuresis, natriuresis, and vasodilation, and can be measured with a blood laboratory assay test or point-of-care testing. BNP/NT proBNP has been most extensively studied in the diagnosis and management of heart failure, but within the past 5 years, interest has carried over to vascular surgery patients. Studies have demonstrated that elevated levels of BNP/NT-proBNP (typically >100 pg/mL/>300 pg/mL) are associated with major adverse cardiac events at 30 and 180 days. Additional analysis of BNP/NT-proBNP has demonstrated that patients can be classified as very low risk (<19 pg/mL), low risk (<100 pg/mL), intermediate risk (100 to 400 pg/mL), or high risk (>400 pg/mL). BNP/NT-proBNP in the low- and very-low-risk groups suggests patients are unlikely to have a major adverse cardiac event. An elevated BNP/NT-proBNP, excluding those with reasons for abnormal values, suggests the need for additional risk stratification and medical risk factor optimization. A preoperative measure of BNP or NT-proBNP affords an easy and rapid opportunity to individually and objectively quantify perioperative cardiovascular risk. Recent studies have also identified other biomarkers, none superior to BNP or NT-proBNP, but that, when used concomitantly, aid in further stratifying perioperative risk and will likely be the focus of future investigations. PMID:26073822

  2. Plasma atrial natriuretic peptide and N-terminal pro B-type natriuretic peptide concentrations in dogs with right-sided congestive heart failure

    PubMed Central

    KANNO, Nobuyuki; HORI, Yasutomo; HIDAKA, Yuichi; CHIKAZAWA, Seishiro; KANAI, Kazutaka; HOSHI, Fumio; ITOH, Naoyuki

    2015-01-01

    The clinical utility of plasma natriuretic peptide concentrations in dogs with right-sided congestive heart failure (CHF) remains unclear. We investigated whether plasma levels of atrial natriuretic peptide (ANP) and N-terminal pro B-type natriuretic peptide (NT-proBNP) are useful for assessing the congestive signs of right-sided heart failure in dogs. This retrospective study enrolled 16 healthy dogs and 51 untreated dogs with presence (n=28) or absence (n=23) of right-sided CHF. Medical records of physical examinations, thoracic radiography and echocardiography were reviewed. The plasma concentration of canine ANP was measured with a chemiluminescent enzyme immunoassay. Plasma NT-proBNP concentrations were determined using an enzyme immunoassay. Plasma ANP and NT-proBNP concentrations in dogs with right-sided CHF were significantly higher than in healthy controls and those without right-sided CHF. The plasma NT-proBNP concentration >3,003 pmol/l used to identify right-sided CHF had a sensitivity of 88.5% and specificity of 90.3%. An area under the ROC curve (AUC) was 0.93. The AUC for NT-proBNP was significantly higher than the AUCs for the cardiothoracic ratio, vertebral heart score, ratio of right ventricular end-diastolic internal diameter to body surface area, tricuspid late diastolic flow and ratio of the velocities of tricuspid early to late diastolic flow. These results suggest that plasma ANP and NT-proBNP concentrations increase markedly in dogs with right-sided CHF. Particularly, NT-proBNP is simple and helpful biomarkers to assess the right-sided CHF. PMID:26607133

  3. NT pro B type natriuretic peptide levels in constrictive pericarditis and restrictive cardiomyopathy

    PubMed Central

    Parakh, Neeraj; Mehrotra, Sameer; Seth, Sandeep; Ramakrishnan, S.; Kothari, Shyam S.; Bhargava, Balram; Bahl, V.K.

    2015-01-01

    Background The differentiation of constrictive pericarditis (CP) from restrictive cardiomyopathy (RCM) may be clinically difficult and may require multiple investigations. Even though brain natriuretic peptide (BNP) is shown to be higher in patients with RCM as compared to CP, the clinical utility is not fully established especially in Indian patients known to have advanced CP and myocardial involvement. Methods and results We measured NT-pro-BNP levels in 49 patients suspected of having either CP or RCM, diagnosed on the basis of echocardiography, computed tomography, magnetic resonance imaging, endomyocardial biopsy and cardiac catheterization data as needed. Twenty nine patients (Mean age – 26 yrs, 24 males) had CP and 20 patients (Mean age – 39 yrs, 14 males) had RCM. The median plasma NT-pro-BNP levels were significantly higher in RCM as compared to CP [1775 (208–7500) pg/ml vs 124 (68–718) pg/ml, respectively; p = 0.001]. A cut off value of 459 pg/ml had sensitivity, specificity and overall accuracy of 90%, 86% and 88% respectively, for differentiating CP from RCM. Conclusions The NT-pro-BNP levels are significantly elevated in RCM as compared to CP. PMID:25820049

  4. B-type natriuretic peptide and amino-terminal pro-B-type natriuretic peptide in pediatric patients with pulmonary arterial hypertension

    PubMed Central

    Takatsuki, Shinichi; Wagner, Brandie D; Ivy, David Dunbar

    2011-01-01

    Objectives B-type natriuretic peptide (BNP) and the amino-terminal fragment (NTproBNP) correlate with clinical variables, but have not been simultaneously studied in a large number of pediatric patients with pulmonary arterial hypertension (PAH). The purpose of our investigation was to compare BNP and NTproBNP with clinical indicators of disease in a pediatric PAH population for which biomarkers are much needed. Design We retrospectively compared BNP and NTproBNP levels with exercise capacity, echocardiographic data, and hemodynamics in PAH patients under 21 years-old. Two hundred sixty three blood samples from 88 pediatric PAH patients were obtained, with BNP and NTproBNP drawn at the same time. Results There was a correlation between BNP and NTproBNP with mean pulmonary arterial pressure/mean arterial pressure (mPAP/mSAP) ratio (r=0.40 p<0.01, r=0.45 p<0.01, respectively), mean right atrial pressure (mRAP) (r=0.48 p<0.01, r=0.48 p<0.01), and tricuspid regurgitant (TR) velocity (r=0.36 p<0.01, r=0.41 p<0.01). BNP and NTproBNP are associated with 6 minute walking distance, mPAP, mPAP/mSAP ratio, mRAP, pulmonary vascular resistance index (PVRI), and TR velocity when investigated longitudinally. On the average, a 1 unit increase in log BNP or NTproBNP was associated with 4.5 unitsxm2 or 3.4 unitsxm2 increase in PVRI, respectively. There was a strong correlation between log BNP and log NTproBNP measurements (r= 0.87, p<0.01). Conclusion In pediatric PAH, BNP and NTProBNP are strongly correlated and predict changes in clinical variables and hemodynamics. In a cross-sectional analysis, NTproBNP correlated with echocardiographic and exercise data better than BNP; NTproBNP showed less within patient variability over time, therefore NTproBNP can add additional information towards predicting these clinical measurements. PMID:22325151

  5. N-terminal pro-B-type natriuretic peptide as a marker of blunt cardiac contusion in trauma.

    PubMed

    Dogan, Halil; Sarikaya, Sezgin; Neijmann, Sebnem Tekin; Uysal, Emin; Yucel, Neslihan; Ozucelik, Dogac Niyazi; Okuturlar, Yıldız; Solak, Suleyman; Sever, Nurten; Ayan, Cem

    2015-01-01

    Cardiac contusion is usually caused by blunt chest trauma and, although it is potentially a life-threatening condition, the diagnosis of a myocardial contusion is difficult because of non-specific symptoms and the lack of an ideal test to detect myocardial damage. Cardiac enzymes, such as creatine kinase (CK), creatine kinase MB fraction (CK-MB), cardiac troponin I (cTn-I), and cardiac troponin T (cTn-T) were used in previous studies to demonstrate the blunt cardiac contusion (BCC). Each of these diagnostic tests alone is not effective for diagnosis of BCC. The aim of this study was to investigate the serum heart-type fatty acid binding protein (h-FABP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), CK, CK-MB, and cTn-I levels as a marker of BCC in blunt chest trauma in rats. The eighteen Wistar albino rats were randomly allocated to two groups; group I (control) (n=8) and group II (blunt chest trauma) (n=10). Isolated BCC was induced by the method described by Raghavendran et al. (2005). All rats were observed in their cages and blood samples were collected after five hours of trauma for the analysis of serum h-FABP, NT-pro BNP, CK, CK-MB, and cTn-I levels. The mean serum NT-pro BNP was significantly different between group I and II (10.3 ± 2.10 ng/L versus 15.4 ± 3.68 ng/L, respectively; P=0.0001). NT-pro BNP level >13 ng/ml had a sensitivity of 87.5%, a specificity of 70%, a positive predictive value of 70%, and a negative predictive value of 87.5% for predicting blunt chest trauma (area under curve was 0.794 and P=0.037). There was no significant difference between two groups in serum h-FABP, CK, CK-MB and c Tn-I levels. A relation between NT-Pro BNP and BCC was shown in this study. Serum NT-proBNP levels significantly increased with BCC after 5 hours of the blunt chest trauma. The use of NT-proBNP as an adjunct to other diagnostic tests, such as troponins, electrocardiography (ECG), chest x-ray and echocardiogram may be beneficial for diagnosis of

  6. N-terminal pro b-type natriuretic peptide (NT-pro-BNP) –based score can predict in-hospital mortality in patients with heart failure

    PubMed Central

    Huang, Ya-Ting; Tseng, Yuan-Teng; Chu, Tung-Wei; Chen, John; Lai, Min-Yu; Tang, Woung-Ru; Shiao, Chih-Chung

    2016-01-01

    Serum N-terminal pro b-type natriuretic peptide (NT-pro-BNP) testing is recommended in the patients with heart failure (HF). We hypothesized that NT-pro-BNP, in combination with other clinical factors in terms of a novel NT-pro BNP-based score, may provide even better predictive power for in-hospital mortality among patients with HF. A retrospective study enrolled adult patients with hospitalization-requiring HF who fulfilled the predefined criteria during the period from January 2011 to December 2013. We proposed a novel scoring system consisting of several independent predictors including NT-pro-BNP for predicting in-hospital mortality, and then compared the prognosis-predictive power of the novel NT-pro BNP-based score with other prognosis-predictive scores. A total of 269 patients were enrolled in the current study. Factors such as “serum NT-pro-BNP level above 8100 mg/dl,” “age above 79 years,” “without taking angiotensin converting enzyme inhibitors/angiotensin receptor blocker,” “without taking beta-blocker,” “without taking loop diuretics,” “with mechanical ventilator support,” “with non-invasive ventilator support,” “with vasopressors use,” and “experience of cardio-pulmonary resuscitation” were found as independent predictors. A novel NT-pro BNP-based score composed of these risk factors was proposed with excellent predictability for in-hospital mortality. The proposed novel NT-pro BNP-based score was extremely effective in predicting in-hospital mortality in HF patients. PMID:27411951

  7. N-terminal pro b-type natriuretic peptide (NT-pro-BNP) -based score can predict in-hospital mortality in patients with heart failure.

    PubMed

    Huang, Ya-Ting; Tseng, Yuan-Teng; Chu, Tung-Wei; Chen, John; Lai, Min-Yu; Tang, Woung-Ru; Shiao, Chih-Chung

    2016-01-01

    Serum N-terminal pro b-type natriuretic peptide (NT-pro-BNP) testing is recommended in the patients with heart failure (HF). We hypothesized that NT-pro-BNP, in combination with other clinical factors in terms of a novel NT-pro BNP-based score, may provide even better predictive power for in-hospital mortality among patients with HF. A retrospective study enrolled adult patients with hospitalization-requiring HF who fulfilled the predefined criteria during the period from January 2011 to December 2013. We proposed a novel scoring system consisting of several independent predictors including NT-pro-BNP for predicting in-hospital mortality, and then compared the prognosis-predictive power of the novel NT-pro BNP-based score with other prognosis-predictive scores. A total of 269 patients were enrolled in the current study. Factors such as "serum NT-pro-BNP level above 8100 mg/dl," "age above 79 years," "without taking angiotensin converting enzyme inhibitors/angiotensin receptor blocker," "without taking beta-blocker," "without taking loop diuretics," "with mechanical ventilator support," "with non-invasive ventilator support," "with vasopressors use," and "experience of cardio-pulmonary resuscitation" were found as independent predictors. A novel NT-pro BNP-based score composed of these risk factors was proposed with excellent predictability for in-hospital mortality. The proposed novel NT-pro BNP-based score was extremely effective in predicting in-hospital mortality in HF patients. PMID:27411951

  8. Head-to-head comparison of B-type natriuretic peptide (BNP) and NT-proBNP in daily clinical practice.

    PubMed

    Mair, Johannes; Gerda, Falkensammer; Renate, Hiemetzberger; Ulmer, Hanno; Andrea, Griesmacher; Pachinger, Otmar

    2008-02-29

    B-type natriuretic peptide (BNP; Abbott Diagnostics) and N-terminal proBNP (NT-proBNP, Roche Diagnostics) were compared in consecutive samples of 458 patients (mean age 60 years+/-16 years; 159 female, 299 male) sent for NT-proBNP measurement to investigate influences on both markers. BNP and NT-proBNP showed a close correlation with each other (r=0.89, p<0.0001). Using age- and gender-adjusted upper reference values the inter-rater agreement of both parameters was satisfactory (83%, Cohen's kappa coefficient=0.7). The combination of normal BNP and elevated NT-proBNP was significantly more frequent than vice versa (61 vs. 16 patients), and a calculated glomerular filtration rate<60 ml/min/1.73 m(2) was found in 39% of these patients. Multiple linear regression analysis revealed a significant influence of a reduced ejection fraction (<50%), renal dysfunction (calculated glomerular filtration rate<60 ml/min/1.73 m(2)), anemia, hypertension, age, and gender on both BNP and NT-proBNP. In conclusion, despite a close correlation and a satisfactory agreement between both markers in classification, frequent discrepancies in individual patients demonstrate that both markers are clinically not completely equivalent. PMID:17360054

  9. Changes in N-terminal pro-B-type natriuretic peptide and incidence of diabetes: The Multi-Ethnic Study of Atherosclerosis (MESA)

    PubMed Central

    Sanchez, O.A.; Duprez, D.A.; Bahrami, H.; Peralta, C.A.; Daniels, L.B.; Lima, J.A.; Maisel, A.; Folsom, A.R.; Jacobs, D.R.

    2016-01-01

    Aims This study looked at whether the inverse association of circulating N-terminal pro-B-type natriuretic peptide (NT-proBNP) with incident diabetes is modified by changes in NT-proBNP (ΔNT-proBNP) levels. Methods lasma NT-proBNP was assayed at baseline and 3.2 years later (visit 3) in the Multi-Ethnic Study of Atherosclerosis (MESA).ΔNT-proBNP was calculated as NT-proBNPvisit3 − NT-proBNPbaseline. A Poisson distribution was fitted to determine the incidence density of diabetes, adjusted for age, race, gender, educational attainment, antihypertensive medication, total intentional exercise and plasma IL-6 levels. In the primary analysis (n = 3236 without diabetes up to visit 3, followed for a mean of 6.3 years), incidence density was regressed for the following categories of baseline NT-proBNP: (1) <54.4 pg/mL; (2) 54.4–85.9 pg/mL; and (3) 86–54.2 pg/mL. This was crossed with categories of ΔNT-proBNP as medians (ranges): (1) −6.2 (−131–11.7) pg/mL; (2) 19.8 (11.8–30.1) pg/mL; (3) 44.0 (30.2–67.9) pg/mL; and (4) 111.2 (68.0–3749.9) pg/mL. Results The incidence density of diabetes followed a U-shaped association across categories of ΔNT-proBNP within categories of baseline NT-proBNP after adjusting for other covariates (P = 0.02). At each level of baseline NT-proBNP, the incidence density of diabetes was lowest for small-to-moderate increases in NT-proBNP. Conclusion This analysis suggests that NT-proBNP has a biphasic association with diabetes in which the risk of incident diabetes decreases within a ‘physiological range’ of ΔNT-proBNP, and plateaus or increases as NT-proBNP concentrations increase, probably in response to pathophysiological conditions leading to high levels of NT-proBNP. PMID:26047677

  10. Serum N-Terminal Pro-B-Type Natriuretic Peptide Levels Are Associated With Functional Capacity in Patients With Peripheral Arterial Disease

    PubMed Central

    Fan, Jin; Jouni, Hayan; Khaleghi, Mahyar; Bailey, Kent R.; Kullo, Iftikhar J.

    2013-01-01

    We hypothesized that higher serum levels of N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) are associated with lower functional capacity in patients with peripheral arterial disease ([PAD] n = 481, mean age 67, 68% men). Functional capacity was quantified as distance walked on a treadmill for 5 minutes. Patients were divided into 3 groups according to the distance walked: >144 yards (group I, n = 254); 60 to 144 yards (group 2, n = 80); <60 yards or did not walk (group 3, n = 147). The association between NT-pro-BNP levels and the ordinal 3-level walking distance was assessed using multivariable ordinal logistic regression analyses that adjusted for several possible confounding variables. Higher levels of NT-pro-BNP were associated with a lower ordinal walking category independent of possible confounders (odds ratio [OR] 1.51, 95% confidence interval [CI] 1.28-1.77; P < .001). In conclusion, higher levels of NT-pro-BNP are independently associated with lower functional capacity in patients with PAD and may be a marker of hemodynamic stress in these patients. PMID:22096207

  11. Predictive Values of N-Terminal Pro-B-Type Natriuretic Peptide and Cardiac Troponin I for Myocardial Fibrosis in Hypertrophic Obstructive Cardiomyopathy

    PubMed Central

    Zhang, Changlin; Liu, Rong; Yuan, Jiansong; Cui, Jingang; Hu, Fenghuan; Yang, Weixian; Zhang, Yan; Chen, Youzhou; Qiao, Shubin

    2016-01-01

    Background Both high-sensitivity cardiac troponin T and B-type natriuretic peptide are useful in detecting myocardial fibrosis, as determined by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR), in patients with non-obstructive hypertrophic cardiomyopathy. However, their values to predict myocardial fibrosis in hypertrophic obstructive cardiomyopathy (HOCM) remain unclear. We investigated the role of N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) and cardiac troponin I (cTnI) to identify LGE-CMR in patients with HOCM. Methods Peripheral concentrations of NT-proBNP and cTnI were determined in patients with HOCM (n = 163; age = 47.2 ± 10.8 years; 38.7% females). Contrast-enhanced CMR was performed to identify and quantify myocardial fibrosis. Results LGE was detected in 120 of 163 patients (73.6%). Patients with LGE had significantly higher levels of NT-proBNP and cTnI than those without LGE (1386.2 [904.6–2340.8] vs. 866.6 [707.2–1875.2] pmol/L, P = 0.003; 0.024 [0.010–0.049] vs. 0.010 [0.005–0.021] ng/ml, P <0.001, respectively). The extent of LGE was positively correlated with log cTnI (r = 0.371, P <0.001) and log NT-proBNP (r = 0.211, P = 0.007). On multivariable analysis, both log cTnI and maximum wall thickness (MWT) were independent predictors of the presence of LGE (OR = 3.193, P = 0.033; OR = 1.410, P < 0.001, respectively), whereas log NT-proBNP was not. According to the ROC curve analysis, combined measurements of MWT ≥21 mm and/or cTnI ≥0.025ng/ml indicated good diagnostic performance for the presence of LGE, with specificity of 95% or sensitivity of 88%. Conclusions Serum cTnI is an independent predictor useful for identifying myocardial fibrosis, while plasma NT-proBNP is only associated with myocardial fibrosis on univariate analysis. Combined measurements of serum cTnI with MWT further improve its value in detecting myocardial fibrosis in patients with HOCM. PMID:26765106

  12. N-Terminal Pro-B Type Natriuretic Peptide as a Marker of Bronchopulmonary Dysplasia or Death in Very Preterm Neonates: A Cohort Study

    PubMed Central

    Sellmer, Anna; Hjortdal, Vibeke Elisabeth; Bjerre, Jesper Vandborg; Schmidt, Michael Rahbek; McNamara, Patrick J.; Bech, Bodil Hammer; Henriksen, Tine Brink

    2015-01-01

    Background Bronchopulmonary dysplasia (BPD) is a serious complication of preterm birth. Plasma N-terminal pro-B type natriuretic peptide (NT-proBNP) has been suggested as a marker that may predict BPD within a few days after birth. Objectives To investigate the association between NT-proBNP day three and bronchopulmonary dysplasia (BPD) or death and further to assess the impact of patent ductus arteriosus (PDA) on this association in neonates born before 32 gestational weeks. Methods A cohort study of 183 neonates born before 32 gestational weeks consecutively admitted to the Neonatal Intensive Care Unit, Aarhus University Hospital, Denmark. On day three plasma samples were collected and echocardiography carried out. NT-proBNP was measured by routine immunoassays. The combined outcome BPD or death was assessed at 36 weeks of postmenstrual age. Receiver operator characteristic (ROC) analysis was performed to determine the discrimination ability of NT-proBNP by the natural log continuous measure to recognize BPD or death. The association of BPD or death was assessed in relation to natural log NT-proBNP levels day three. Results The risk of BPD or death increased 1.7-fold with one unit increase of natural log NT-proBNP day three when adjusted for gestational age at birth (OR = 1.7, 95% CI 1.3; 2.3). The association was found both in neonates with and without a PDA. Adjusting for GA, PDA diameter, LA:Ao-ratio, or early onset sepsis did not change the estimate. Conclusion We found NT-proBNP to be associated with BPD or death in very preterm neonates. This association was not only explained by the PDA. We speculate that NT-proBNP may help the identification of neonates at risk of BPD as early as postnatal day three. PMID:26452045

  13. Higher Serum Concentrations of N-Terminal Pro-B-Type Natriuretic Peptide Associate with Prevalent Hypertension whereas Lower Associate with Incident Hypertension

    PubMed Central

    Seven, Ekim; Husemoen, Lise L. N.; Ibsen, Hans; Friedrich, Nele; Nauck, Matthias; Wachtell, Kristian; Linneberg, Allan; Jeppesen, Jørgen L.

    2015-01-01

    Background The role of the natriuretic peptides (NPs) in hypertension is complex. Thus, a higher blood NP concentration is a robust marker of pressure-induced cardiac damage in patients with hypertension, whereas genetically elevated NP concentrations are associated with a reduced risk of hypertension and overweight individuals presumably at high risk of hypertension have lower NP concentrations. Objective To investigate the associations between serum N-terminal pro-B-type natriuretic peptide (NT-proBNP), used as a surrogate marker for active BNP, and prevalent as well as 5-year incident hypertension in a Danish general population sample. Methods Cross-sectional and prospective population-based study. Results At baseline, among 5,307 participants (51.3% women, mean age 46.0±7.9 years) with a complete set of data, we recorded 1,979 cases with prevalent hypertension (PHT). Among 2,389 normotensive participants at baseline with a complete set of data, we recorded 324 cases with incident hypertension (IHT) on follow-up 5 years later. In models adjusted for age, sex, lifestyle, social, dietary, anthropometric, pulmonic, lipid, metabolic and renal risk factors, as well as heart rate and baseline blood pressure (only incident model), one standard deviation increase in baseline log-transformed NT-proBNP concentrations was on one side associated with a 21% higher risk of PHT (odds ratio [OR]: 1.21 [95% confidence interval (CI): 1.13-1.30], P<0.001), and on the other side with a 14% lower risk of IHT (OR: 0.86 [95%CI:0.76-0.98], P = 0.020). Conclusions Higher serum concentrations of NT-proBNP associate with PHT whereas lower concentrations associate with IHT. This suggests that a lower amount of circulating BNP, resulting in diminished vasodilation and natriuresis, could be involved in the pathogenesis of hypertension in its early stages. PMID:25658326

  14. Amino-Terminal Pro-B-Type Natriuretic Peptide Improves Discrimination for Incident Atherosclerotic Cardiovascular Disease Beyond Ambulatory Blood Pressure in Elderly Men.

    PubMed

    Skoglund, Per H; Höijer, Jonas; Ärnlöv, Johan; Zethelius, Björn; Svensson, Per

    2015-09-01

    Improvement of risk prediction for atherosclerotic cardiovascular disease (ASCVD) is needed. Both ambulatory blood pressure (ABP) and biomarkers amino-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein and cystatin C improve risk prediction but they have not been evaluated in relation to each other. We analyzed whether NT-proBNP, high-sensitivity C-reactive protein, or cystatin C improved risk prediction beyond traditional ASCVD risk factors combined with 24-hour systolic BP (SBP). Secondary aim was to evaluate whether ABP improved risk prediction when compared with models with the biomarkers. We followed up 907 70-year-old men, free of baseline disease, for incident ASCVD defined as fatal or nonfatal myocardial infarction or fatal or nonfatal stroke for a median of 10 years. Cox regression was used to estimate the association between variables in the models and incident ASCVD. Biomarkers were added to a model containing both traditional risk factors and ABP and the models were compared on C-statistics and net reclassification improvement. Twenty-four hour SBP improved discrimination for incident ASCVD when compared with office SBP in a traditional risk factor model (area under the receiver-operating characteristic curve, +2.4%). NT-proBNP further improved reclassification (+18.7%-19.9%; P<0.01) when added to ABP models, whereas high-sensitivity C-reactive protein and cystatin C did not. Twenty-four hour SBP significantly improved net reclassification when added to a traditional risk factor model that included NT-proBNP. The combination of 24-hour SBP and NT-proBNP improved discrimination and net reclassification for incident ASCVD when compared with office SBP in elderly men. NT-proBNP, but not high-sensitivity C-reactive protein or cystatin C, improved risk prediction and discrimination when added to a model that included ABP. PMID:26150437

  15. N-Terminal Pro-B-Type Natriuretic Peptide Levels Inversely Correlated With Heart Rate Variability in Patients With Unstable Angina Pectoris.

    PubMed

    Dufang, Ma; Yongcheng, Wang; Ping, Jiang; Yonghui, Yin; Xiao, Li

    2016-05-25

    We explored the relationships between heart rate variability (HRV) and levels of N-terminal Pro-B-type natriuretic peptide (NT-proBNP) in patients with unstable angina pectoris (UA).A total of 90 consecutive patients admitted < 48 hours for UA were included. Serum levels of NT-proBNP were measured from blood samples. The cohort was divided into tertiles according to NT-proBNP levels. HRV parameters including SDNN, RMSSD, LF, HF, TP, and VLF were assessed by 24-hour Holter ECG monitoring.The median (IQR) NT-proBNP level was 177.02 (64.76, 740.70) pg/mL. Patients with SDNN < 100 ms had higher levels of NT-proBNP than those with SDNN > 100 ms (P = 0.003). With increasing levels of NT-proBNP, both the 24hour monitoring HRV and night-monitoring HRV showed that SDNN and VLF gradually decreased (P < 0.01), and patients in the NT-proBNP lowest tertile group had higher LF values than the other two groups (P < 0.05); however, no difference was found in RMSSD, HF, and TP. During the daytime, the LF, VLF, and TP values were lower in the NTproBNP highest group compared with the lowest tertile group (P < 0.05). NT-proBNP levels correlated negatively with SDNN (r = -0.314, P = 0.003) and VLF (r = -0.397, P < 0.001) but not with other HRV parameters. Multiple regression analysis showed that serum levels of NT-proBNP remained predictive of SDNN (β = -0.060, P = 0.001) and VLF (β = -0.145, P < 0.001), even after adjustment for confounders.Our study showed that the elevated serum levels of NT-proBNP predict reduced HRV parameters, and the increased NT-proBNP levels combined with decreased HRV represent the degree of neurohormonal dysfunction and may be better prognostic predictors for risk stratification in UA patients. PMID:27170473

  16. Association between serum N-terminal pro-B-type natriuretic peptide levels and characteristics of coronary atherosclerotic plaque detected by coronary computed tomography angiography

    PubMed Central

    Gan, Lu; Feng, Cong; Liu, Chunlei; Tian, Shuping; Song, Xiang; Yang, Li

    2016-01-01

    The aim of the present study was to explore the association between the levels of serum N-terminal pro-B-type natriuretic peptide (NT-pro BNP) and the characteristics of coronary atherosclerotic plaque detected by coronary computed tomography angiography (CCTA), in patients with unstable angina (UA). A total of 202 patients (age range, 47–82 years) were divided into the following three groups: Non-cardiac disease group (57 patients); stable angina pectoris (SAP) group (62 patients); and UA group (83 patients). There were significant differences between the serum NT-pro BNP levels among the three groups (P=0.007). However, in multivariant diagnoses, NT-pro BNP level was not an independent risk factor for UA. The levels of serum NT-pro BNP were observed to be positively correlated with the number of vessels involved (r=0.462; P<0.001), SIS (r=0.475; P<0.001), segment-stenosis score (r=0.453; P<0.001), coronary calcification score (r=0.412; P=0.001), number of obstructive diseases (r=0.346; P<0.001), and the number of segments with non-calcified plaque (r=0.235; P=0.017), mixed plaque (r=0.234; P=0.017) and calcified plaque (r=0.431; P<0.001). The levels of serum NT-pro BNP were significantly higher in patients with UA and left main-left anterior descending (LM-LAD) disease, compared with UA patients without LM-LAD disease (P<0.001). In addition, serum NT-pro BNP was significantly higher in patients with obstructive disease and UA than in those without obstructive disease (P<0.001). The area under the curve of log(NT-pro BNP) was 0.656 (P=0.006; optimal cut-off value, 1.74; sensitivity, 77.6%; specificity, 51.9%). In conclusion, the levels of serum NT-pro BNP are associated with the burden and severity of coronary artery atherosclerotic disease in patients with UA, and may be helpful in risk stratification of patients with UA. PMID:27446259

  17. Correlation between B type natriuretic peptide and metabolic risk factors

    PubMed Central

    Zhu, Wen-Hua; Chen, Li-Ying; Dai, Hong-Lei; Chen, Jian-Hua; Chen, Yan

    2016-01-01

    Introduction It has been shown that B type natriuretic peptide (BNP) level can indicate cardiovascular disease. However, the association between BNP and metabolic risk factors is unknown. The aim of this study was to investigate the correlation between N-terminal pro-B type natriuretic peptide (NT-proBNP) and metabolic risk factors. Material and methods A total of 11,508 subjects were selected from those who underwent health examinations in our hospital. NT-proBNP, waist circumference, blood pressure, fasting plasma glucose and lipid profile were measured. The level of NT-proBNP was measured and classified into four stratifications (BNP ≥ 20 pg/ml, ≥ 40 pg/ml, ≥ 60 pg/ml, and ≥ 80 pg/ml) to analyze the relationship between BNP and metabolic risk factors. Results B type natriuretic peptide increased gradually with increasing age (p < 0.001). The BNP levels were significantly higher in women than in men (p < 0.001). Multivariate regression analysis showed a positive association between NT-proBNP levels and systolic blood pressure (p < 0.001), fasting plasma glucose (p < 0.05), and total cholesterol (p < 0.001 in women). The NT-proBNP levels were inversely associated with diastolic blood pressure, waist circumference, triglyceride, high-density lipoprotein, and LDL cholesterol. Logistic regression analysis demonstrated a close relationship between NT-proBNP and systolic blood pressure, fasting plasma glucose, and total cholesterol. In the BNP ≥ 60 pg/ml group, odds ratio (OR) values were 1.80, 1.56 and 1.54 (female) and 3.74, 1.59 and 1.51 (male), respectively. In the BNP ≥ 80 pg/ml group, OR values were 2.45, 1.65 and 1.84 (female) and 4.61, 1.66 and 1.75 (male), respectively. Conclusions NT-proBNP was independently associated with the main metabolic risk factors (systolic blood pressure, fasting plasma glucose, and total cholesterol). These findings suggest that the combined determination of NT-proBNP and the main metabolic risk factors could be

  18. Atrial natriuretic peptide, B-type natriuretic peptide, and serum collagen markers after acute myocardial infarction.

    PubMed

    Magga, Jarkko; Puhakka, Mikko; Hietakorpi, Seppo; Punnonen, Kari; Uusimaa, Paavo; Risteli, Juha; Vuolteenaho, Olli; Ruskoaho, Heikki; Peuhkurinen, Keijo

    2004-04-01

    Experimental data suggest that atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) act locally as antifibrotic factors in heart. We investigated the interrelationships of natriuretic peptides and collagen markers in 93 patients receiving thrombolytic treatment for their first acute myocardial infarction (AMI). Collagen formation following AMI, evaluated as serum levels of amino terminal propeptide of type III procollagen, correlated with NH(2)-terminal proANP (r = 0.45, P < 0.001), BNP (r = 0.55, P < 0.001) and NH(2)-terminal proBNP (r = 0.50, P < 0.01) on day 4 after thrombolysis. Levels of intact amino terminal propeptide of type I procollagen decreased by 34% (P < 0.001), and levels of carboxy terminal cross-linked telopeptide of type I collagen (ICTP) increased by 65% (P < 0.001). ICTP levels correlated with NH(2)-terminal proBNP (r = 0.25, P < 0.05) and BNP (r = 0.28, P < 0.05) on day 4. Our results suggest that ANP and BNP may act as regulators of collagen scar formation and left ventricular remodeling after AMI in humans. Furthermore, degradation of type I collagen is increased after AMI and may be regulated by BNP. PMID:14607848

  19. Evaluation of N-terminal pro-B-type natriuretic peptide and high-sensitivity C-reactive protein relationship with features of metabolic syndrome in high-risk subgroups for cardiovascular disease

    PubMed Central

    Nayak, Bijoor Shivananda; Jagessar, Avinas; Mohammed, Zaryd; Rampersad, Jarryd; Ramkissoon, Solange; Biswah, Shivonne; Mohammed, Amisha; Maraj, Aneela; Rampersad, Christina

    2015-01-01

    Aim: This study evaluating N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) and high-sensitivity C-reactive protein (hs-CRP) relationship with features of the metabolic syndrome (MS) in high risk subgroups for cardiovascular disease (CVD) in Trinidad. Materials and Methods: The sample population consisted of 160 subjects, 78 of whom were African and 82 East Indian attending medical outpatient clinics of regional health authority hospitals of Trinidad. Results: Systolic blood pressure, triglycerides, glucose and insulin as well as NT-pro-BNP were elevated among the East Indian sub-population, with only systolic blood pressure being significantly elevated among the African sub-population. NT-pro-BNP and hs-CRP demonstrated significant correlations with respect to the majority of independent risk factors inclusive of Adult Treatment Panel III and American Association of Clinical Endocrinologists defined criteria for MS. NT-pro-BNP demonstrated stronger association among the East Indian sub-population as compared to that of the African sub-population. Conclusions: Our study showed that the East Indian subgroup was more at risk for CVD as evidenced by the fulfillment of the criteria for diagnosis of MS and therefore NT-pro-BNP and hs-CRP can be deemed a suitable marker for MS. PMID:26539369

  20. Influence of renal function on the usefulness of N-terminal pro-B-type natriuretic peptide as a prognostic cardiac risk marker in patients undergoing noncardiac vascular surgery.

    PubMed

    Goei, Dustin; Schouten, Olaf; Boersma, Eric; Welten, Gijs M J M; Dunkelgrun, Martin; Lindemans, Jan; van Gestel, Yvette R B M; Hoeks, Sanne E; Bax, Jeroen J; Poldermans, Don

    2008-01-01

    N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) is related to stress-induced myocardial ischemia and/or volume overload, both common in patients with renal dysfunction. This might compromise the prognostic usefulness of NT-pro-BNP in patients with renal impairment before vascular surgery. We assessed the prognostic value of NT-pro-BNP in the entire strata of renal function. In 356 patients (median age 69 years, 77% men), cardiac history, glomerular filtration rate (GFR, ml/min/1.73 m(2)), and NT-pro-BNP level (pg/ml) were assessed preoperatively. Troponin T and electrocardiography were assessed postoperatively on days 1, 3, 7, and 30. The end point was the composite of cardiovascular death, Q-wave myocardial infarction, and troponin T release. Multivariate analysis was used to evaluate the interaction between GFR, NT-pro-BNP and their association with postoperative outcome. Median GFR was 78 ml/min/1.73 m(2) and the median concentration of NT-pro-BNP was 197 pg/ml. The end point was reached in 64 patients (18%); cardiac death occurred in 7 (2.0%), Q-wave myocardial infarction in 34 (9.6%), and non-Q-wave myocardial infarction in 23 (6.5%). After adjustment for confounders, NT-pro-BNP levels and GFR remained significantly associated with the end point (p = 0.005). The prognostic value of NT-pro-BNP was most pronounced in patients with GFR > or =90 (odds ratio [OR] 1.18, 95% confidence interval [CI] 0.80 to 1.76) compared with patients with GFR 60 to 89 (OR 1.04, 95% CI 1.002 to 1.07), and with GFR 30 to 59 (OR 1.12, 95% CI 1.03 to 1.21). In patients with GFR <30 ml/min/1.73 m(2), NT-pro-BNP levels have no prognostic value (OR 1.00, 95% CI 0.99 to 1.01). In conclusion, the discriminative value of NT-pro-BNP is most pronounced in patients with GFR > or =90 ml/min/1.73 m(2) and has no prognostic value in patients with GFR <30 ml/min/1.73 m(2). PMID:18157978

  1. N-terminal pro B type natriuretic peptide in high cardiovascular-risk patients for noncardiac surgery: What is the current prognostic evidence?

    PubMed Central

    Malhotra, Anita K.; Ramakrishna, Harish

    2016-01-01

    As millions of surgical procedures are performed worldwide on an aging population with multiple comorbidities, accurate and simple perioperative risk stratification is critical. The cardiac biomarker, brain natriuretic peptide (BNP), has generated considerable interest as it is easy to obtain and appears to have powerful predictive and prognostic capabilities. BNP is currently being used to guide medical therapy for heart failure and has been added to several algorithms for perioperative risk stratification. This review examines the current evidence for the use of BNP in the perioperative period in patients who are at high-cardiovascular risk for noncardiac surgery. In addition, we examined the use of BNP in patients with pulmonary embolism and left ventricular assist devices. The available data strongly suggest that the addition of BNP to perioperative risk calculators is beneficial; however, whether this determination of risk will impact outcomes, remains to be seen. PMID:27052075

  2. The Effects of Super-Flux (High Performance) Dialyzer on Plasma Glycosylated Pro-B-Type Natriuretic Peptide (proBNP) and Glycosylated N-Terminal proBNP in End-Stage Renal Disease Patients on Dialysis

    PubMed Central

    Nakagawa, Yasuaki; Nishikimi, Toshio; Kuwahara, Koichiro; Yasuno, Shinji; Kinoshita, Hideyuki; Kuwabara, Yoshihiro; Nakao, Kazuhiro; Minami, Takeya; Yamada, Chinatsu; Ueshima, Kenji; Ikeda, Yoshihiro; Okamoto, Hiroyuki; Horii, Kazukiyo; Nagata, Kiyoshi; Kangawa, Kenji; Minamino, Naoto; Nakao, Kazuwa

    2014-01-01

    Background Plasma BNP levels are predictive of prognosis in hemodialysis patients. However, recent studies showed that the current BNP immunoassay cross-reacts with glycosylated proBNP, and the NT-proBNP assay underestimates glycosylated NT-proBNP. In addition, the recently developed high performance dialyzer removes medium-sized molecular solutes such as β2-microgloburin. We therefore investigated the effects of high performance dialysis on measured levels of glycosylated proBNP, glycosylated NT-proBNP and other BNP-related peptides in end-stage renal disease (ESRD) patients on hemodialysis. Method The relationships between clinical parameters and BNP-related molecule were also investigated. We used our newly developed immunoassay to measure plasma total BNP and proBNP in 105 normal subjects and 36 ESRD patients before and after hemodialysis. Plasma NT-proBNP was measured using Elecsys II after treatment with or without deglycosylating enzymes. We also measured plasma ANP and cGMP using radioimmunoassays. Results All the measured BNP-related peptides were significantly higher in ESRD patients than healthy subjects. Total BNP (−38.9%), proBNP (−29.7%), glycoNT-proBNP (−45.5%), nonglycoNT-proBNP (−53.4%), ANP (−50.4%) and cGMP (−72.1%) were all significantly reduced after hemodialysis, and the magnitude of the reduction appeared molecular weight- dependent. Both the proBNP/total BNP and glycoNT-proBNP/nonglycoNT-proBNP ratios were increased after hemodialysis. The former correlated positively with hemodialysis vintage and negatively with systolic blood pressure, while the latter correlated positively with parathyroid hormone levels. Conclusion These results suggest that hemodialysis using super-flux dialyzer removes BNP-related peptides in a nearly molecular weight-dependent manner. The ProBNP/total BNP and glycoNT-proBNP/nonglycoNT-proBNP ratios appear to be influenced by hemodialysis-related parameters in ESRD patients on hemodialysis. PMID:24667631

  3. B-type Natriuretic Peptide circulating forms: Analytical and bioactivity issues.

    PubMed

    Yandle, Tim G; Richards, A Mark

    2015-08-25

    B-type Natriuretic Peptide (BNP), A-type and C-type Natriuretic Peptides (ANP and CNP) comprise a family of peptides that retain a common ring structure and conserved amino acid sequences. All are present in the heart, but only BNP and ANP are regarded as primarily cardiac secretory products. BNP and ANP, acting through a guanylyl cyclase receptor, increase sodium and water excretion by the kidney, induce vasodilation, reduce blood pressure, counteract the bioactivity of the renin-angiotensin-aldosterone and sympathetic nervous systems and possess anti-hypertrophic and anti-fibrotic properties. BNP is synthesised in cardiomyocytes first as the precursor peptide preproBNP. Removal of the signal peptide from preproBNP produces proBNP which is cleaved to produce the biologically active carboxy-terminal BNP peptide and the inactive N-terminal fragment, NT-proBNP. BNP, NT-proBNP, proBNP and the C-terminal portion of the BNP signal peptide have been detected in human plasma as well as multiple sub-forms including truncated forms of BNP and NT-proBNP, as well as variable glycosylation of NT-proBNP and proBNP. The origin of these circulating forms, their potential bioactivity and their detection by current analytical methods are presented in this review. PMID:26160054

  4. Clinical implications of defective B-type natriuretic peptide.

    PubMed

    Menon, Santosh G; Mills, Roger M; Schellenberger, Ute; Saqhir, Syed; Protter, Andrew A

    2009-12-01

    Our understanding of the natriuretic peptide system continues to evolve rapidly. B-type natriuretic peptide (BNP), originally thought to be a simple volume-regulating hormone that is produced in response to cardiac stretch, has been shown to also play important roles in modulating bronchodilation, endothelial function, and cardiac remodeling. Recent data demonstrate that elevated levels of BNP in patients with heart failure do not represent a simple ratcheting up of normal production in response to increased stimulus. Instead, we now know that chronic stimulation of BNP synthesis induces a reversion to fetal gene expression, resulting in production of high molecular weight forms of BNP that are functionally deficient. Standard point-of-care BNP assays are immunoassays that will detect any molecule containing the target epitopes. Consequently, these assays cannot distinguish between defective, high molecular weight forms of BNP and normal, physiologically active BNP. In 2 separate evaluations, mass spectroscopy detected little, if any, normal BNP in patients with heart failure, despite the appearance of high circulating levels of immunoreactive BNP (iBNP) using commercial assays. Therefore, these commercial assays should be considered to be only an indication of myocardial stress. They do not measure physiologic BNP activity. This accounts for the "BNP paradox," namely, that administration of exogenous recombinant human BNP (rhBNP, nesiritide) has substantial clinical and hemodynamic impact in the presence of high levels of circulating iBNP using commercial assays. In addition to its short-term hemodynamic impact, rhBNP may have other important effects in this setting, and further investigation is warranted. PMID:20014209

  5. The precursor to B-type natriuretic peptide is an O-linked glycoprotein.

    PubMed

    Schellenberger, Ute; O'Rear, Jessica; Guzzetta, Andrew; Jue, Rodney A; Protter, Andrew A; Pollitt, N Stephen

    2006-07-15

    Human pro-B-type natriuretic peptide (proBNP), the precursor for B-type natriuretic peptide (BNP), was expressed in Chinese hamster ovary cells (CHO) and compared by Western blot analysis to BNP cross-reacting material immunoprecipitated from the plasma of heart failure patients. Both recombinant and native forms co-migrated as a diffuse band centered around 25 kDa and were reduced to a 12 kDa species by treatment with a mixture of O-link deglycosylation enzymes. The 108-amino acid CHO-expressed protein was examined by tryptic mapping and LC-MS and found to be an O-linked glycoprotein. Determination of the sites of O-glycosyl addition by blank cycle sequencing of tryptic and Glu-C (Staphylococcus aureus V8 protease) peptides showed that there are seven sites of glycosylation confined to a 36-amino acid residue stretch within the center of the propeptide region. This data is consistent with previous observations of higher molecular weight isoforms of BNP. PMID:16750161

  6. Impact of Modifiable Risk Factors on B-type Natriuretic Peptide and Cardiac Troponin T Concentrations.

    PubMed

    Srivastava, Pratyaksh K; Pradhan, Aruna D; Cook, Nancy R; Ridker, Paul M; Everett, Brendan M

    2016-02-01

    Alcohol use, physical activity, diet, and cigarette smoking are modifiable cardiovascular risk factors that have a substantial impact on the risk of myocardial infarction, stroke, and cardiovascular death. We hypothesized that these behaviors may alter concentrations of cardiac troponin, a marker of myocyte injury, and B-type natriuretic peptide, a marker of myocyte stress. Both markers have shown strong association with adverse cardiovascular outcomes. In 519 women with no evidence of cardiovascular disease, we measured circulating concentrations of cardiac troponin T, using a high-sensitivity assay (hsTnT), and the N-terminal fragment of B-type natriuretic peptide (NT-proBNP). We used logistic regression to determine if these behaviors were associated with hsTnT ≥ 3 ng/l or with NT-proBNP in the highest quartile (≥ 127.3 ng/l). The median (Q1 to Q3) NT-proBNP of the cohort was 68.8 ng/l (40.3 to 127.3 ng/l), and 30.8% (160 of 519) of the cohort had circulating hsTnT ≥ 3 ng/l. In adjusted models, women who drank 1 to 6 drinks/week had lower odds of having a hsTnT ≥ 3 ng/l (odds ratio 0.58, 95% confidence interval 0.34 to 0.96) and lower odds of having an elevated NT-proBNP (odds ratio 0.55, 95% confidence interval 0.32 to 0.96). We were subsequently able to validate the results for B-type natriuretic peptide in a large independent cohort. In conclusion, our results suggest that regular alcohol consumption is associated with lower concentrations of hsTnT and NT-proBNP, 2 cardiovascular biomarkers associated with cardiovascular risk, and raise the hypothesis that the beneficial effects of alcohol consumption may be mediated by direct effects on the myocardium. PMID:26739393

  7. Monitoring B-type natriuretic peptide in patients undergoing therapy with neprilysin inhibitors. An emerging challenge?

    PubMed

    Lippi, Giuseppe; Sanchis-Gomar, Fabian

    2016-09-15

    B-type natriuretic peptide (BNP) is primarily synthesized by the ventricles of the heart as a 108-amino acid polypeptide precursor (i.e., proBNP), which is then cleaved into a 76-amino acid biologically inert N-terminal fragment (NT-proBNP) and a biologically active 32-amino acid peptide (BNP). The generation of BNP is considerably enhanced in response to high ventricular filling pressures, so that the measurement of either the active hormone or NT-proBNP has become a mainstay in patients with congestive heart failure. Recent evidence was brought that the enzyme neprilysin efficiently degrades circulating BNP in vivo, whereas proBNP and NT-proBNP are virtually resistant to enzymatic cleavage. Increasing emphasis is currently placed on the fact that that measuring BNP in patients taking the novel and promising neprilysin inhibitors such as LCZ696 may not reliably reflect cardiac dysfunction. Since laboratory monitoring in patients with heart failure should be aimed to define the role of BNP in modulating fluid hemostasis and cardiac remodeling, but natriuretic peptides should also serve as reliable biomarkers of cardiac function and treatment response in these patients, the assessment of neither BNP nor NT-proBNP alone provides a comprehensive biological and clinical picture. Therefore, it seems reasonable to suggest both BNP and the neprilysin-resistant peptide NT-proBNP should be concomitantly assessed in patients with heart failure who take neprilysin inhibitors, so allowing to concomitantly monitor the progression of heart failure and to assess the actual cardiorenal potency of circulating BNP. PMID:27317994

  8. BNP and NT-proBNP Test

    MedlinePlus

    ... Peptides Formal name: B-type Natriuretic Peptide; N-terminal pro b-type Natriuretic Peptide Related tests: Cardiac ... for B-type natriuretic peptide (BNP) or N-terminal pro b-type natriuretic peptide (NT-proBNP) is ...

  9. 21 CFR 862.1117 - B-type natriuretic peptide test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false B-type natriuretic peptide test system. 862.1117 Section 862.1117 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  10. 21 CFR 862.1117 - B-type natriuretic peptide test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false B-type natriuretic peptide test system. 862.1117 Section 862.1117 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  11. 21 CFR 862.1117 - B-type natriuretic peptide test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false B-type natriuretic peptide test system. 862.1117 Section 862.1117 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  12. 21 CFR 862.1117 - B-type natriuretic peptide test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false B-type natriuretic peptide test system. 862.1117 Section 862.1117 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  13. 21 CFR 862.1117 - B-type natriuretic peptide test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false B-type natriuretic peptide test system. 862.1117 Section 862.1117 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  14. Reduced immunoreactivities of B-type natriuretic peptide in pulmonary arterial hypertension rats after ranolazine treatment

    PubMed Central

    Lee, Jae Chul; Kim, Kwan Chang

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a severe pulmonary vascular disease characterized by sustained increase in the pulmonary arterial pressure and excessive thickening and remodeling of the distal small pulmonary arteries. During disease progression, structural remodeling of the right ventricular (RV) impairs pump function, creates pro-arrhythmic substrates and triggers for arrhythmias. Notably, RV failure and lethal arrhythmias are major contributors to cardiac death in PAH that are not directly addressed by currently available therapies. Ranolazine (RAN) is an anti-anginal, anti-ischemic drug that has cardioprotective effects of heart dysfunction. RAN also has anti-arrhythmic effects due to inhibition of the late sodium current in cardiomyocytes. Therefore, we hypothesized that RAN could reduce the mal-adaptive structural remodeling of the RV, and prevent triggered ventricular arrhythmias in the monocrotaline-induced rat model of PAH. RAN reduced ventricular hypertrophy, reduced levels of B-type natriuretic peptide, and decreased the expression of fibrosis. In addition, RAN prevented cardiovascular death in rat model of PAH. These results support the notion that RAN can improve the functional properties of the RV, highlighting its potential benefits in the setting of heart impairment. PMID:27051563

  15. Reduced immunoreactivities of B-type natriuretic peptide in pulmonary arterial hypertension rats after ranolazine treatment.

    PubMed

    Lee, Jae Chul; Kim, Kwan Chang; Choe, Soo Young; Hong, Young Mi

    2016-03-01

    Pulmonary arterial hypertension (PAH) is a severe pulmonary vascular disease characterized by sustained increase in the pulmonary arterial pressure and excessive thickening and remodeling of the distal small pulmonary arteries. During disease progression, structural remodeling of the right ventricular (RV) impairs pump function, creates pro-arrhythmic substrates and triggers for arrhythmias. Notably, RV failure and lethal arrhythmias are major contributors to cardiac death in PAH that are not directly addressed by currently available therapies. Ranolazine (RAN) is an anti-anginal, anti-ischemic drug that has cardioprotective effects of heart dysfunction. RAN also has anti-arrhythmic effects due to inhibition of the late sodium current in cardiomyocytes. Therefore, we hypothesized that RAN could reduce the mal-adaptive structural remodeling of the RV, and prevent triggered ventricular arrhythmias in the monocrotaline-induced rat model of PAH. RAN reduced ventricular hypertrophy, reduced levels of B-type natriuretic peptide, and decreased the expression of fibrosis. In addition, RAN prevented cardiovascular death in rat model of PAH. These results support the notion that RAN can improve the functional properties of the RV, highlighting its potential benefits in the setting of heart impairment. PMID:27051563

  16. Prediction of clinical outcomes using B-type natriuretic peptides in the general population: a systematic review.

    PubMed

    Don-Wauchope, Andrew C; Santaguida, Pasqualina L; McKelvie, Robert; Brown, Judy A; Oremus, Mark; Ali, Usman; Bustamam, Amy; Sohel, Nazmul; Hill, Stephen A; Booth, Ronald A; Balion, Cynthia; Raina, Parminder

    2014-08-01

    The use of B-type natriuretic peptides to predict outcomes in general populations has been investigated in a number of primary studies. A previous systematic review considering natriuretic peptides in cardiovascular disease included a subgroup of general population studies, which suggested an association with a number of clinical outcomes. We electronically searched Medline, Embase, AMED, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and CINAHL for English-language articles published between 1989 and mid-2012. We utilized trained reviewers and standardized forms to screen articles for inclusion and extract data from included articles. All included studies (n = 7) were summarized in narrative and tabular form. A general population was defined as one that was randomly selected from a community setting where no specific inclusion or exclusion criteria were specified. The seven included studies all used FDA approved assays for NT-proBNP. The range of clinical outcomes and heterogeneity did not allow for meta-analysis. The hazard ratios for predicting outcomes in the included studies ranged from 1.0 to 4.1 (all p values <0.05). The discrimination statistics reported in four studies all demonstrated statistically significant improvements in predicting outcomes. NT-proBNP is associated with heart failure, all-cause and cardiovascular mortality, and other combined cardiovascular events in a general unselected population. The discrimination statistics suggest modest improvements in risk stratification. No prospective studies exist to demonstrate the clinical utility of using B-type natriuretic peptides to predict clinical outcomes in a general population. PMID:25052419

  17. B-type natriuretic peptide and C-reactive protein in the prediction of atrial fibrillation risk: the CHARGE-AF Consortium of community-based cohort studies

    PubMed Central

    Sinner, Moritz F.; Stepas, Katherine A.; Moser, Carlee B.; Krijthe, Bouwe P.; Aspelund, Thor; Sotoodehnia, Nona; Fontes, João D.; Janssens, A. Cecile J.W.; Kronmal, Richard A.; Magnani, Jared W.; Witteman, Jacqueline C.; Chamberlain, Alanna M.; Lubitz, Steven A.; Schnabel, Renate B.; Vasan, Ramachandran S.; Wang, Thomas J.; Agarwal, Sunil K.; McManus, David D.; Franco, Oscar H.; Yin, Xiaoyan; Larson, Martin G.; Burke, Gregory L.; Launer, Lenore J.; Hofman, Albert; Levy, Daniel; Gottdiener, John S.; Kääb, Stefan; Couper, David; Harris, Tamara B.; Astor, Brad C.; Ballantyne, Christie M.; Hoogeveen, Ron C.; Arai, Andrew E.; Soliman, Elsayed Z.; Ellinor, Patrick T.; Stricker, Bruno H.C.; Gudnason, Vilmundur; Heckbert, Susan R.; Pencina, Michael J.; Benjamin, Emelia J.; Alonso, Alvaro

    2014-01-01

    Aims B-type natriuretic peptide (BNP) and C-reactive protein (CRP) predict atrial fibrillation (AF) risk. However, their risk stratification abilities in the broad community remain uncertain. We sought to improve risk stratification for AF using biomarker information. Methods and results We ascertained AF incidence in 18 556 Whites and African Americans from the Atherosclerosis Risk in Communities Study (ARIC, n=10 675), Cardiovascular Health Study (CHS, n = 5043), and Framingham Heart Study (FHS, n = 2838), followed for 5 years (prediction horizon). We added BNP (ARIC/CHS: N-terminal pro-B-type natriuretic peptide; FHS: BNP), CRP, or both to a previously reported AF risk score, and assessed model calibration and predictive ability [C-statistic, integrated discrimination improvement (IDI), and net reclassification improvement (NRI)]. We replicated models in two independent European cohorts: Age, Gene/Environment Susceptibility Reykjavik Study (AGES), n = 4467; Rotterdam Study (RS), n = 3203. B-type natriuretic peptide and CRP were significantly associated with AF incidence (n = 1186): hazard ratio per 1-SD ln-transformed biomarker 1.66 [95% confidence interval (CI), 1.56–1.76], P < 0.0001 and 1.18 (95% CI, 1.11–1.25), P < 0.0001, respectively. Model calibration was sufficient (BNP, χ2 = 17.0; CRP, χ2 = 10.5; BNP and CRP, χ2 = 13.1). B-type natriuretic peptide improved the C-statistic from 0.765 to 0.790, yielded an IDI of 0.027 (95% CI, 0.022–0.032), a relative IDI of 41.5%, and a continuous NRI of 0.389 (95% CI, 0.322–0.455). The predictive ability of CRP was limited (C-statistic increment 0.003). B-type natriuretic peptide consistently improved prediction in AGES and RS. Conclusion B-type natriuretic peptide, not CRP, substantially improved AF risk prediction beyond clinical factors in an independently replicated, heterogeneous population. B-type natriuretic peptide may serve as a benchmark to evaluate novel putative AF risk biomarkers. PMID:25037055

  18. Usefulness of B-type Natriuretic Peptides to Predict Cardiovascular Events in Women (from the Women's Health Study).

    PubMed

    Everett, Brendan M; Ridker, Paul M; Cook, Nancy R; Pradhan, Aruna D

    2015-08-15

    Natriuretic peptides are positively associated with incident cardiovascular disease (CVD), but data in women, particularly with regard to improvements in risk prediction, are sparse. We measured the N-terminal prohormone form of B-type natriuretic peptide (NT-proBNP) in 480 cases of incident CVD (myocardial infarction, stroke, and cardiovascular death) and a reference subcohort of 564 women from the Women's Health Study who were followed for a median of 12.0 (interquartile range 7.6 to 13.4) years. Median (interquartile range) NT-proBNP concentrations were greater in women who developed CVD (81 ng/l [50 to 147]) than those who did not (64 ng/l [38 to 117]; p <0.0001). For women in the highest compared to the lowest quartile, NT-proBNP was 65% greater after adjusting for established cardiovascular risk factors and kidney function (adjusted hazard ratio [aHR] 1.65, 95% confidence interval [CI] 1.03 to 2.64, p trend = 0.03). When analyzed as a continuous variable, the aHR per 1 - SD difference in Ln(NT-proBNP) was 1.22 (1.03 to 1.44; p = 0.02). The per 1 - SD change in Ln(NT-proBNP) appeared stronger for cardiovascular death (aHR 1.43, 95% CI 1.05 to 1.94, p = 0.02) and stroke (aHR 1.24, 95% CI 1.03 to 1.50, p = 0.03) than myocardial infarction (aHR 1.09, 95% CI 0.87 to 1.37, p = 0.44). When added to traditional risk co-variables, NT-proBNP did not significantly improve the C-statistic (0.751 to 0.757; p = 0.09) or net reclassification into <5%, 5 to <7.5%, and ≥7.5% 10-year CVD risk categories (0.014; p = 0.18). In conclusion, in this prospective study of initially healthy women, NT-proBNP concentrations showed statistically significant association with incident CVD that was independent of traditional cardiovascular risk factors but did not substantially improve measures of CVD risk prediction. PMID:26081066

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

    PubMed

    Skov, Jeppe; Holst, Jens Juul; Gøtze, Jens Peter; Frøkiær, Jørgen; Christiansen, Jens Sandahl

    2014-01-01

    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. PMID:24327600

  20. Effect of B-type natriuretic peptides on long-term outcomes after transcatheter aortic valve implantation.

    PubMed

    Koskinas, Konstantinos C; O'Sullivan, Crochan J; Heg, Dik; Praz, Fabien; Stortecky, Stefan; Pilgrim, Thomas; Buellesfeld, Lutz; Jüni, Peter; Windecker, Stephan; Wenaweser, Peter

    2015-11-15

    B-type natriuretic peptide (BNP) levels are elevated in patients with aortic stenosis (AS) and decrease acutely after replacement of the stenotic valve. The long-term prognostic value of BNP after transcatheter aortic valve implantation (TAVI) and the relative prognostic utility of single versus serial peri-interventional measurements of BNP and N-terminal prohormone BNP (NT-pro-BNP) are unknown. This study sought to determine the impact of BNP levels on long-term outcomes after TAVI and to compare the utility of BNP versus NT-pro-BNP measured before and after intervention. We analyzed 340 patients with severe AS and baseline pre-TAVI assessment of BNP. In 219 patients, BNP and NT-pro-BNP were measured serially before and after intervention. Clinical outcomes over 2 years were recorded. Patients with high baseline BNP (higher tertile ≥591 pg/ml) had increased risk of all-cause mortality (adjusted hazard ratio 3.16, 95% confidence interval 1.84 to 5.42; p <0.001) and cardiovascular death at 2 years (adjusted hazard ratio 3.37, 95% confidence interval 1.78 to 6.39; p <0.001). Outcomes were most unfavorable in patients with persistently high BNP before and after intervention. Comparing the 2 biomarkers, NT-pro-BNP levels measured after TAVI showed the highest prognostic discrimination for 2-year mortality (area under the curve 0.75; p <0.01). Baseline-to-discharge reduction, but not baseline levels of BNP, was related to New York Heart Association functional improvement. In conclusion, high preintervention BNP independently predicts 2-year outcomes after TAVI, particularly when elevated levels persist after the intervention. BNP and NT-pro-BNP and their serial periprocedural changes provide complementary prognostic information for symptomatic improvement and survival. PMID:26428025

  1. A review on B-type natriuretic peptide monitoring: assays and biosensors.

    PubMed

    Maalouf, Rita; Bailey, Steven

    2016-09-01

    Since its discovery in 1988, B-type natriuretic peptide (BNP) has been recognized as a powerful cardiovascular biomarker for a number of disease states, specifically heart failure. Concurrent with such a discovery, much effort has been allocated to the precise monitoring of physiological BNP levels. Thus, it can be used to guide the therapy of heart failure and determine the patient's stage of disease. Thus, we discuss in this article BNP as a potent biomarker. Subsequently, we will review the progress of biosensing devices as they could be applied to monitor BNP levels as assays, benchtop biosensors and implantable biosensors. The analytical characteristics of commercially available BNP assays are presented. Still emerging as a field, we define four obstacles that present opportunity for the future development of implantable biosensor: foreign body response, sensor renewability, sensitivity and selectivity. PMID:26979601

  2. Mendelian Randomization Study of B-Type Natriuretic Peptide and Type 2 Diabetes: Evidence of Causal Association from Population Studies

    PubMed Central

    Pfister, Roman; Sharp, Stephen; Luben, Robert; Welsh, Paul; Barroso, Inês; Salomaa, Veikko; Meirhaeghe, Aline; Khaw, Kay-Tee; Sattar, Naveed; Langenberg, Claudia; Wareham, Nicholas J.

    2011-01-01

    Background Genetic and epidemiological evidence suggests an inverse association between B-type natriuretic peptide (BNP) levels in blood and risk of type 2 diabetes (T2D), but the prospective association of BNP with T2D is uncertain, and it is unclear whether the association is confounded. Methods and Findings We analysed the association between levels of the N-terminal fragment of pro-BNP (NT-pro-BNP) in blood and risk of incident T2D in a prospective case-cohort study and genotyped the variant rs198389 within the BNP locus in three T2D case-control studies. We combined our results with existing data in a meta-analysis of 11 case-control studies. Using a Mendelian randomization approach, we compared the observed association between rs198389 and T2D to that expected from the NT-pro-BNP level to T2D association and the NT-pro-BNP difference per C allele of rs198389. In participants of our case-cohort study who were free of T2D and cardiovascular disease at baseline, we observed a 21% (95% CI 3%–36%) decreased risk of incident T2D per one standard deviation (SD) higher log-transformed NT-pro-BNP levels in analysis adjusted for age, sex, body mass index, systolic blood pressure, smoking, family history of T2D, history of hypertension, and levels of triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. The association between rs198389 and T2D observed in case-control studies (odds ratio = 0.94 per C allele, 95% CI 0.91–0.97) was similar to that expected (0.96, 0.93–0.98) based on the pooled estimate for the log-NT-pro-BNP level to T2D association derived from a meta-analysis of our study and published data (hazard ratio = 0.82 per SD, 0.74–0.90) and the difference in NT-pro-BNP levels (0.22 SD, 0.15–0.29) per C allele of rs198389. No significant associations were observed between the rs198389 genotype and potential confounders. Conclusions Our results provide evidence for a potential causal role of the BNP

  3. B-Type Natriuretic Peptide Levels Predict Ventricular Arrhythmia Post Left Ventricular Assist Device Implantation.

    PubMed

    Hellman, Yaron; Malik, Adnan S; Lin, Hongbo; Shen, Changyu; Wang, I-Wen; Wozniak, Thomas C; Hashmi, Zubair A; Pickrell, Jeanette; Jani, Milena; Caccamo, Marco A; Gradus-Pizlo, Irmina; Hadi, Azam

    2015-12-01

    B-type natriuretic peptide (BNP) levels have been shown to predict ventricular arrhythmia (VA) and sudden death in patients with heart failure. We sought to determine whether BNP levels before left ventricular assist device (LVAD) implantation can predict VA post LVAD implantation in advanced heart failure patients. We conducted a retrospective study consisting of patients who underwent LVAD implantation in our institution during the period of May 2009-March 2013. The study was limited to patients receiving a HeartMate II or HeartWare LVAD. Acute myocardial infarction patients were excluded. We compared between the patients who developed VA within 15 days post LVAD implantation to the patients without VA. A total of 85 patients underwent LVAD implantation during the study period. Eleven patients were excluded (five acute MI, four without BNP measurements, and two discharged earlier than 13 days post LVAD implantation). The incidence of VA was 31%, with 91% ventricular tachycardia (VT) and 9% ventricular fibrillation. BNP remained the single most powerful predictor of VA even after adjustment for other borderline significant factors in a multivariate logistic regression model (P < 0.05). BNP levels are a strong predictor of VA post LVAD implantation, surpassing previously described risk factors such as age and VT in the past. PMID:25864448

  4. Arterial Remodeling in B-Type Natriuretic Peptide Knock-Out Females.

    PubMed

    Holditch, Sara J; Schreiber, Claire A; Burnett, John C; Ikeda, Yasuhiro

    2016-01-01

    Sexual dimorphisms are recognized in cardiovascular conditions such as hypertension, stroke, thrombosis and vasculitis. B-type natriuretic peptide (BNP) is a guanylyl cyclase A (GC-A) agonist. The anti-hypertensive, vasodilatory, anti-fibrotic, and anti-hypertrophic properties of BNP are well established in male animal models. Although circulating BNP levels are higher in women, when compared to age-matched men, the cardiovascular protective propensity of BNP in females is poorly understood. We assessed the cardiovascular consequences of BNP deletion in genetically null (Nppb-/-) female rat lines. Throughout the study, blood pressure (BP) remained uninfluenced by genotype, and cardiorenal consequences of BNP knock out remained minor. Unexpectedly, approximately 60% of Nppb-/- females developed mesenteric polyarteritis-nodosa (PAN)-like vasculitis in their life span, some as early as 4 months of age. Mesenteric lesions involved intense arterial remodeling, progressive inflammation, occluded lumens, and less frequently intestinal necrosis and multiple visceral arterial aneurysms. Cumulative pathologies resulted in a significant decline in survival of the Nppb-/- female. This study highlights BNP's vasoprotective propensity, bringing to light a possible sex specific difference in the cardiovascular protection provided by BNP. Defects in the BNP/GC-A/cGMP pathway may play a role in arteriopathies in women, while GC-A agonists may provide effective therapy for arteritis. PMID:27162120

  5. Arterial Remodeling in B-Type Natriuretic Peptide Knock-Out Females

    PubMed Central

    Holditch, Sara J.; Schreiber, Claire A.; Burnett, John C.; Ikeda, Yasuhiro

    2016-01-01

    Sexual dimorphisms are recognized in cardiovascular conditions such as hypertension, stroke, thrombosis and vasculitis. B-type natriuretic peptide (BNP) is a guanylyl cyclase A (GC-A) agonist. The anti-hypertensive, vasodilatory, anti-fibrotic, and anti-hypertrophic properties of BNP are well established in male animal models. Although circulating BNP levels are higher in women, when compared to age-matched men, the cardiovascular protective propensity of BNP in females is poorly understood. We assessed the cardiovascular consequences of BNP deletion in genetically null (Nppb−/−) female rat lines. Throughout the study, blood pressure (BP) remained uninfluenced by genotype, and cardiorenal consequences of BNP knock out remained minor. Unexpectedly, approximately 60% of Nppb−/− females developed mesenteric polyarteritis-nodosa (PAN)-like vasculitis in their life span, some as early as 4 months of age. Mesenteric lesions involved intense arterial remodeling, progressive inflammation, occluded lumens, and less frequently intestinal necrosis and multiple visceral arterial aneurysms. Cumulative pathologies resulted in a significant decline in survival of the Nppb−/− female. This study highlights BNP’s vasoprotective propensity, bringing to light a possible sex specific difference in the cardiovascular protection provided by BNP. Defects in the BNP/GC-A/cGMP pathway may play a role in arteriopathies in women, while GC-A agonists may provide effective therapy for arteritis. PMID:27162120

  6. Serum B-type natriuretic peptide levels as a marker for anthracycline-induced cardiotoxicity

    PubMed Central

    WANG, YA-DI; CHEN, SU-XIAN; REN, LI-QUN

    2016-01-01

    Observational and experimental studies have produced inconsistent evidence about the association of serum levels of B-type natriuretic peptide (BNP) with anthracycline-induced cardiotoxicity (AIC). Therefore, the current meta-analysis examined the association between serum BNP levels and AIC by using data from high quality studies published in peer-reviewed journals. Relevant studies were identified through literature searches of China National Knowledge Infrastructure (CNKI), Web of Science, PubMed, Google Scolar and China BioMedicine (CBM). STATA software was used in this meta-analysis for statistical analysis. In addition, the crude standardized mean difference (SMD) with 95% confidence interval (CI) for the highest vs. the lowest category of serum BNP levels was calculated. A total of 8 independent case-control studies, containing 126 AIC patients and 569 healthy controls, were included for the current meta-analysis. The results indicated a significant difference in serum BNP levels between the cardiotoxic group and normal group, with respect to post-treatment and pretreatment with anthracyclines. Specifically, the serum levels of BNP increased remarkably after treatment with anthracyclines in the cardiotoxic group, compared with the normal group. No publication bias was detected in this meta-analysis. The findings of the present study provide strong evidence that serum BNP levels may be associated with AIC. PMID:27123140

  7. Regulation of B-type natriuretic peptide synthesis by insulin in obesity in male mice.

    PubMed

    Zhang, Haihua; Thoonen, Robrecht; Yao, Vincent; Buys, Emmanuel S; Popovich, John; Su, Yan Ru; Wang, Thomas J; Scherrer-Crosbie, Marielle

    2016-01-01

    Human studies suggest that insulin resistance and obesity are associated with a decrease in B-type natriuretic peptide (BNP) plasma concentrations. The objective of the study was to gain insights into the mechanisms involved in the association between insulin resistance and decreased BNP plasma concentrations. Mice fed a high-fat, high-fructose (HFHF) diet for 4 weeks developed mild obesity and systemic insulin resistance. Elevated plasma concentrations of insulin, glucose and triglycerides were noted. The HFHF diet was also associated with myocardial insulin resistance, characterized by an impaired response of the phosphoinositide 3-kinase-AKT (PI3K-AKT) pathway to insulin in the left ventricle. Myocardial BNP expression and protein were decreased in HFHF-fed mice compared with control animals. Exposure of cardiomyocytes to 100 nm insulin activated PI3K-AKT signalling (15 min) and induced a 1.9 ± 0.3-fold increase in BNP gene expression (6 h). Prolonged exposure of cardiomyocytes to a high insulin concentration (100 nm) for 48 h induced insulin resistance, characterized by an impaired response of the PI3K-AKT signalling pathway and a decreased response of the BNP gene expression to insulin. The decreased response in BNP gene expression was reproduced by treating cardiomyocytes for 7 h with a PI3-kinase inhibitor (wortmannin). In conclusion, HFHF diet in vivo, prolonged exposure to an elevated concentration of insulin or inhibition of the PI3K-AKT pathway in vitro all decrease BNP mRNA levels; this decrease may in turn contribute to the decreased BNP peptide concentrations in plasma observed in insulin-resistant individuals. PMID:26446173

  8. B-type natriuretic peptide-directed ultrafiltration improves care in acutely hospitalized dialysis patients.

    PubMed

    Tapolyai, Mihály; Uysal, Aşkin; Maeweathers, Gail; Bahta, Elias; Dossabhoy, Neville R

    2009-01-01

    In an observational study in 19 consecutive acutely hospitalized dialysis patients, ultrafiltration (UF) volume was determined by B-type natriuretic peptide (BNP) levels. Patients were ultrafiltrated daily until they achieved a target BNP level <500 pg/mL. The UF volumes ranged from 2 to 5 L per session. All patients were male veterans aged 68+/-11 years (mean +/- SD), 74% were diabetic, 47% were African Americans, 58% underwent prevalent dialysis, and 53% had an arteriovenous fistula. Left ventricular ejection fraction on 2-dimensional echocardiography was 43.8%+/-27.9% (n=16). The admission BNP was 2412+/-1479 pg/mL (range, 561-5000 pg/mL) and BNP at hospital discharge was 1245+/-1173 pg/mL (range, 345-5000 pg/mL) (nonparametric Wilcoxon P=.0013). Admission weight was 88.9+/-27.9 kg and at discharge was 78.1+/-25.6 kg (P=.0002). The number of antihypertensive medications taken was 3.8+/-2.0 at admission and 2.3+/-1.7 at discharge (P=.0005). The number of patients with >2 blood pressure medications decreased from 14 to 6 (Fisher exact test, P=.02). The systolic/diastolic/mean arterial blood pressure decreased from admission to discharge (153.6+/-43.8/80.6+/-21.8/102.4+/-27.3 to 132.1+/-27.9/68.9+/-14.6/89.9+/-16.5 mm Hg; P=.0222/.0139/.0329, respectively). Although all patients were volume-overloaded at admission according to BNP criteria (>500), only 42% were identified as having heart failure. BNP-directed UF is safe because it minimizes symptomatic hypotension, identifies occult congestive heart failure in a large number of patients, and significantly reduces blood pressure in addition to reducing body weight and number of medications used. PMID:19522962

  9. Arg13 of B-Type Natriuretic Peptide Reciprocally Modulates Binding to Guanylyl Cyclase but Not Clearance Receptors

    PubMed Central

    Dickey, Deborah M.; Barbieri, Kathryn A.; McGuirk, Christopher M.

    2010-01-01

    B-type natriuretic peptide (BNP) decreases cardiac preload and hypertrophy. As such, synthetic BNP, nesiritide, was approved for the treatment of acutely decompensated heart failure. However, two problems limit its therapeutic potential. First, ensuing hypertension decreases urine output, and second, guanylyl cyclase-A (GC-A), the primary signaling receptor for BNP, is down-regulated in heart failure. Thus, alternative or chimeric natriuretic peptides maintaining the renal but lacking the vasorelaxation properties of BNP provide an alternative approach. Here, we examined the ability of single amino acid substitutions in the conserved 17-amino acid disulfide ring structure of human BNP to activate GC-A and guanylyl cyclase-B (GC-B), which is not reduced in heart failure. We hypothesized that substitution of highly conserved residues in BNP with highly conserved residues from a GC-B-specific peptide would yield BNP variants with increased and decreased potency for human GC-B and GC-A, respectively. Substitution of Leu for Arg13 (l-bnp) yielded a 5-fold more potent activator of GC-B and 7-fold less potent activator of GC-A compared with wild type. l-bnp also bound GC-A 4.5-fold less tightly than wild type. In contrast, substitution of Met for Ser21 (M-BNP) had no effect. A peptide containing both the Leu and Met substitutions behaved similarly to l-bnp. Meanwhile, wild-type and l-bnp bound the natriuretic peptide clearance receptor with similar affinities. These data indicate that Arg13 of BNP is a critical discriminator of binding to guanylyl cyclase-linked but not clearance natriuretic peptide receptors, supporting designer natriuretic peptides as an alternative to wild-type BNP for the treatment of heart failure. PMID:20530652

  10. B-type Natriuretic Peptide Assay in Differentiating Congestive Heart Failure from Lung Disease in Patients Presenting with Dyspnea.

    PubMed

    Islam, M A; Bari, M S; Islam, M N; Bari, M A; Siddique, S R; Islam, M Z; Begum, M S; Ahammed, S U; Rahman, M A

    2016-07-01

    This cross-sectional analytical study was conducted in Cardiology & Medicine Department of Mymensingh Medical College Hospital. After fulfilling the exclusion & inclusion criteria, B-type natriuretic peptide concentrations were measured in a convenience sample of 100 predominantly male (94%) dyspnic patients who got admitted in Cardiology & Medicine Department of Mymensingh Medical College & Hospital from November 2013 to October 2014. The diagnosis of Congestive Heart Failure (CHF) was based on generally accepted Framingham criteria with corroborative information including hospital course (response to diuretics, vasodilators, inotropes or hemodynamic monitoring) and results of further cardiac testing, including echocardiography. Patients with right heart failure from cor pulmonale were classified as having CHF. Pulmonary disease was confirmed by using the following diagnostic tools: i) A chest X-ray without signs of heart enlargement or pulmonary venous hypertension or a chest X-ray with signs of chronic obstructive lung disease, ii) Normal heart function as seen by echocardiography, iii) Abnormal pulmonary function tests or follow-up results and iv) A positive response to treatment with steroids, nebulizers or antibiotics in hospital. Patients with CHF (n=50) had mean BNP level 1146.72pg/ml (range 103 to 5000pg/ml), which is significantly higher than the group of patients with a final diagnosis of pulmonary disease (n=50) whose BNP was 34pg/ml (range 10 to 90pg/ml) (p<0.05). In conclusion, it was found that B-type natriuretic peptide is an important biomarker for differentiating congestive heart failure from lung disease in patients presenting with dyspnea. PMID:27612893

  11. B-type natriuretic peptide-guided therapy: a systematic review.

    PubMed

    Balion, Cynthia; McKelvie, Robert; Don-Wauchope, Andrew C; Santaguida, Pasqualina L; Oremus, Mark; Keshavarz, Homa; Hill, Stephen A; Booth, Ronald A; Ali, Usman; Brown, Judy A; Bustamam, Amy; Sohel, Nazmul; Raina, Parminder

    2014-08-01

    BNP/NT-proBNP measurement has not gained widespread use for the management of patients with heart failure (HF) despite several randomized controlled trials. A systematic review addressing the question of whether patients with HF benefit from BNP-assisted therapy or intensified therapy compared with usual care was undertaken. Relevant randomized controlled trial (RCTs) were selected by searching Medline, Embase, AMED, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and CINAHL for English-language articles published from 1980 to 2012. Selected studies required patients to be treated for chronic HF with medical therapy based on BNP/NT-proBNP or usual care. There were no restrictions except that BNP/NT-proBNP measurement had to be done by an FDA approved method. Nine RCTs were identified with 2,104 patients with study duration that ranged from 3 to 18 months. Overall, there was a wide variation in study design and how parameters were reported including patient selection, baseline characteristics, therapy goals, BNP/NT-proBNP cutpoint, and outcome types. Meta-analysis was not appropriate given this study heterogeneity. The strength of evidence for the outcome of mortality, reported in seven studies, was found to be low due to inconsistency and imprecision. This systematic review showed that the evidence is of low quality and insufficient to support the use of BNP/NT-proBNP to guide HF therapy. Further trials with improved design are needed. PMID:25074674

  12. High-Sensitivity Troponin I and Amino-Terminal Pro–B-Type Natriuretic Peptide Predict Heart Failure and Mortality in the General Population

    PubMed Central

    McKie, Paul M.; AbouEzzeddine, Omar F.; Scott, Christopher G.; Mehta, Ramila; Rodeheffer, Richard J.; Redfield, Margaret M.; Burnett, John C.; Jaffe, Allan S.

    2015-01-01

    INTRODUCTION High-sensitivity cardiac troponin assays have potent prognostic value in stable cardiovascular disease cohorts. Our objective was to assess the prognostic utility of a novel cardiac troponin I (cTnI) high-sensitivity assay, independently and in combination with amino-terminal pro–B-type natriuretic peptide (NT-proBNP), for the future development of heart failure and mortality in the general community. METHODS A well-characterized community-based cohort of 2042 participants underwent clinical assessment and echocardiographic evaluation. Baseline measurements of cTnI with a high-sensitivity assay and NT-proBNP were obtained in 1843 individuals. Participants were followed for new-onset heart failure and mortality with median (25th, 75th percentile) follow-up of 10.7 (7.9, 11.6) and 12.1 (10.4, 13.0) years, respectively. RESULTS When measured with a high-sensitivity assay, cTnI greater than the sex-specific 80th percentile was independently predictive of heart failure [hazard ratio 2.56 (95% confidence interval 1.88 – 3.50), P < 0.001] and mortality [1.91(1.49 – 2.46), P < 0.001] beyond conventional risk factors in this community-based cohort, with significant increases in the net reclassification improvement for heart failure. The prognostic utility of cTnI measured with a high-sensitivity assay goes beyond NT-proBNP, yet our data suggest that these 2 assays are complementary and most beneficial when evaluated together in identifying at-risk individuals in the community. CONCLUSIONS Our findings lay the foundation for prospective studies aimed at identification of individuals at high risk by use of a multimarker approach, followed by aggressive prevention strategies to prevent subsequent heart failure. PMID:24987112

  13. Correlation of B-type natriuretic peptide levels and echocardiographic parameters in preterm infants with patent ductus arteriosus

    PubMed Central

    Jeong, Hyun Ah; Shin, Jeonghee; Kim, Eunji; Lee, Eun Hee; Son, Chang Sung; Lee, Joo Won

    2016-01-01

    Purpose This study aimed to evaluate the correlation, according to postnatal age, between plasma B-type natriuretic peptide (BNP) levels and echocardiographic parameters for the assessment of patent ductus arteriosus (PDA) in preterm infants with respiratory distress. Methods We enrolled 42 preterm infants with respiratory distress who underwent serial echocardiographic evaluation with simultaneous plasma BNP measurements until ductal closure. The correlations between BNP levels and the following 4 representative echocardiographic parameters were studied: diameter of the ductus arteriosus (DA), ratio of the left atrial diameter to the aortic diameter (LA/Ao), ratio of the PDA diameter to the infant's left pulmonary artery diameter (PDA/LPA), and the antegrade diastolic flow of LPA (DFLPA). Results BNP levels were significantly correlated to the magnitude of the ductal shunt, comprising the DA diameter, PDA/LPA ratio, LA/Ao ratio, and antegrade DFLPA for the overall study period. The earliest significant correlation, starting from postnatal day 2, was observed between the LA/Ao ratio and BNP levels. The PDA/LPA ratio and the antegrade DFLPA showed significant correlations with BNP levels postnatal day 3 onward, and with the DA diameter, postnatal day 5 onward. Conclusion BNP levels and echocardiographic parameters showed a positive correlation, but the significance of the correlations differed according to the postnatal age, especially during the first few days of life. PMID:27186229

  14. Supramaximal elevation in B-type natriuretic peptide and its N-terminal fragment levels in anephric patients with heart failure: a case series

    PubMed Central

    2012-01-01

    Introduction Little is known about the responses of natriuretic peptides to developing congestive heart failure in ‘anephric’ end-stage kidney disease. Case presentation We present three consecutive cases of surgically-induced anephric patients in a critical care environment: a 28-year-old Caucasian woman (with congestive heart failure), a 42-year-old Caucasian woman (without congestive heart failure), and a 23-year-old Caucasian woman (without congestive heart failure). Our limited study data indicate that cut-off values advocated for B-type natriuretic peptide and its N-terminal fragment to ‘rule out’ congestive heart failure in two of our end-stage kidney disease patients (without congestive heart failure) are largely appropriate for anephric patients. However, our index (first) patient developed congestive heart failure accompanied by the phenomenon of massive and persistent elevation of these natriuretic levels. Conclusion Our findings suggest that patients from the anephric subclass suffering from congestive heart failure will develop supramaximal elevation of B-type natriuretic peptide and its N-terminal fragment, implying the need for dramatically higher cut-off values with respective magnitudes of the order of 50-fold (B-type natriuretic peptide ~5780pmol/L; 20,000ng/L) to 100-fold (N-terminal fragment ~11,800pmol/L; 100,000ng/L) higher than current values used to ‘rule in’ congestive heart failure. Further research will be required to delineate those cut-off values. The role of our devised ‘Blood Volume – B-type natriuretic peptide feedback control system’ on ‘anatomical’ and ‘functional’ anephric patients led to significant mathematically-enriched arguments supporting our proposal that this model provides plausible explanations for the study findings, and the model lends support to the important hypothesis that these two groups of anephric patients inflicted with congestive heart failure should effectively have similar

  15. Increased B-type-natriuretic peptide promotes myocardial cell apoptosis via the B-type-natriuretic peptide/long non-coding RNA LSINCT5/caspase-1/interleukin 1β signaling pathway

    PubMed Central

    ZHANG, XIAN; SHA, MINGLEI; YAO, YUTING; DA, JIA; JING, DADAO

    2015-01-01

    Chronic heart failure (CHF) is the final stage of various heart diseases, and is increasingly recognized as a major health problem in the elderly. Previous studies demonstrated that B-type-natriuretic peptide (BNP) is an established biomarker of CHF. Furthermore, BNP also regulates cell proliferation, differentiation and apoptosis. Recent evidence has revealed that BNP affects myocardial cell apoptosis during myocardial ischemia-reperfusion injury. Long non-coding RNAs (lncRNAs) are emerging as novel molecular compounds involved in gene regulation, and have important roles in numerous human diseases. However, the mechanism underlying the BNP and lncRNA-induced regulation of myocardial cell apoptosis remains to be elucidated. The present study reported that lncRNA LSINCT5, upregulated by BNP, is able to regulate myocardial cell apoptosis via the activation of the caspase-1/interleukin (IL)-1β signaling pathway. BNP-induced apoptosis of HCM cells was observed using flow cytometry, and involved caspase-1. In addition, expression profiling using a human lncRNA polymerase chain reaction array revealed that LSINCT5 was highly expressed in BNP-treated myocardial cells, as compared with untreated cells. The role of lncRNA LSINCT5 in HCM cell apoptosis was also investigated. The results of the present study indicated that LSINCT5 silencing by small interfering RNA inhibits caspase-1/IL-1β signaling, and suppresses apoptosis in BNP-treated HCM cells. Therefore, high expression levels of BNP promote the apoptosis of myocardial cells through the lncRNA LSINCT5 mediator, which activates the caspase-1/IL-1β signaling pathway. These findings uncovered a novel pathogenic mechanism, and provided a potential therapeutic target for CHF. PMID:26323562

  16. Clinical chemistry and clinical toxicology devices; classification of B-type natriuretic peptide test system. Food and Drug Administration, HHS. Final rule.

    PubMed

    2001-02-28

    The Food and Drug Administration (FDA) is classifying the B-type natriuretic peptide (BNP) test system into class II (special controls). The special control that will apply to this device is a guidance document entitled "Class II Special Control Guidance Document for B-Type Natriuretic Peptide Premarket Notifications; Final Guidance for Industry and FDA Reviewers." The agency is taking this action in response to a petition submitted under the Federal Food, Drug, and Cosmetic Act (the act) as amended by the Medical Device Amendments of 1976, the Safe Medical Devices Act of 1990, and the Food and Drug Administration Modernization Act of 1997. The agency is classifying these devices into class II (special controls) in order to provide a reasonable assurance of the safety and effectiveness of the device. PMID:11503864

  17. Correlation between B-Type Natriuretic Peptide and Functional/Cognitive Parameters in Discharged Congestive Heart Failure Patients

    PubMed Central

    Leto, Laura; Testa, Marzia; Feola, Mauro

    2015-01-01

    The determination of B-type natriuretic peptides (BNP) may have a role in the diagnosis of heart failure (HF) or guiding HF therapy. This study investigated the role of BNP determination in a cohort of elderly patients admitted to hospital with acute decompensated HF and its correlation with main demographic, clinical, and instrumental data and evaluated possible association with major outcome such as mortality or readmission after a 6-month period of follow-up. Methods. From October 2011 to May 2014 consecutive patients admitted to our unit with symptoms of acute HF or worsening of chronic HF entered the study collecting functional, echocardiographic, and hydration parameters. Correlation between BNP and main parameters was analysed, as well as the mortality/6-month readmission rate. Results. In 951 patients (mean age 71 ys; 37% females) a positive correlation was obtained between BNP and age, creatinine levels, NYHA class at admission and discharge, and levels of hydration; an inverse, negative correlation between BNP and sodium levels, LVEF, distance performed at 6MWT at admission and at discharge, and scores at MMSE at admission and discharge emerged. BNP levels at admission and at discharge were furthermore clearly associated with mortality at 6 months (Chi-square 704.38, p = 0.03) and hospital readmission (Chi-square 741.57, p < 0.01). Conclusion. In an elderly HF population, BNP is related not only with clinical, laboratory, and instrumental data but also with multidimensional scales evaluating global status; higher BNP levels are linked with a worse prognosis in terms of mortality and 6-month readmission. PMID:25977690

  18. Efficacy of B-Type Natriuretic Peptide Is Coupled to Phosphodiesterase 2A in Cardiac Sympathetic Neurons

    PubMed Central

    Li, Dan; Lu, Chieh-Ju; Hao, Guoliang; Wright, Hannah; Woodward, Lavinia; Liu, Kun; Vergari, Elisa; Surdo, Nicoletta C.; Herring, Neil; Zaccolo, Manuela; Paterson, David J.

    2015-01-01

    Elevated B-type natriuretic peptide (BNP) regulates cGMP-phosphodiesterase activity. Its elevation is regarded as an early compensatory response to cardiac failure where it can facilitate sympathovagal balance and cardiorenal homeostasis. However, recent reports suggest a paradoxical proadrenergic action of BNP. Because phosphodiesterase activity is altered in cardiovascular disease, we tested the hypothesis that BNP might lose its efficacy by minimizing the action of cGMP on downstream pathways coupled to neurotransmission. BNP decreased norepinephrine release from atrial preparations in response to field stimulation and also significantly reduced the heart rate responses to sympathetic nerve stimulation in vitro. Using electrophysiological recording and fluorescence imaging, BNP also reduced the depolarization evoked calcium current and intracellular calcium transient in isolated cardiac sympathetic neurons. Pharmacological manipulations suggested that the reduction in the calcium transient was regulated by a cGMP/protein kinase G pathway. Fluorescence resonance energy transfer measurements for cAMP, and an immunoassay for cGMP, showed that BNP increased cGMP, but not cAMP. In addition, overexpression of phosphodiesterase 2A after adenoviral gene transfer markedly decreased BNP stimulation of cGMP and abrogated the BNP responses to the calcium current, intracellular calcium transient, and neurotransmitter release. These effects were reversed on inhibition of phosphodiesterase 2A. Moreover, phosphodiesterase 2A activity was significantly elevated in stellate neurons from the prohypertensive rat compared with the normotensive control. Our data suggest that abnormally high levels of phosphodiesterase 2A may provide a brake against the inhibitory action of BNP on sympathetic transmission. PMID:25916722

  19. Clinical value of plasma B-type natriuretic peptide assay in pediatric pneumonia accompanied by heart failure

    PubMed Central

    HU, DAN; LIU, YANG; TAO, HUIXIAN; GAO, JINPING

    2015-01-01

    Previous studies have shown that B-type natriuretic peptide (BNP) is useful in differentiating cardiac from pulmonary causes of dyspnea in adults. To date, international guidelines have recommended measurements of circulating BNP as a biomarker for diagnostic and prognostic purposes, as well as therapeutic monitoring, in adults with cardiac diseases, particularly those suffering from acute and chronic heart failure (HF). The aim of the present study was to investigate the differential diagnostic and therapeutic analysis of BNP levels assayed in pediatric pneumonia accompanied by HF. The clinical data of 80 patients with pneumonia, aged 1–3 years, were analyzed. The patients were divided into two groups: Simple pneumonia (46 cases) and pneumonia accompanied by HF (34 cases). All patients underwent two plasma BNP assays: The first one upon admission to the hospital and the second one prior to discharge. The plasma BNP levels of 20 healthy children were used as the negative control. Plasma BNP levels were measured using the Triage® BNP automated immunoassay systems and reagents. Statistical analysis showed that the plasma BNP levels of the patients upon admission were higher in the pneumonia accompanied by HF group compared with those in the simple pneumonia group (750±120 vs. 135±50 pg/ml; P<0.05). In addition, in the pneumonia accompanied by HF group, the plasma BNP levels of the patients were higher upon admission to the hospital than they were prior to discharge (750±120 vs. 115±45 pg/ml; P<0.05); therefore, plasma BNP may comprise a sensitive diagnostic and therapeutic evaluative marker for pediatric patients with pneumonia accompanied by HF. This finding could prove invaluable in the clinical diagnosis and treatment of the disease. PMID:26668612

  20. The Expression of B-Type Natriuretic Peptide After CaCl2-Induced Arrhythmias in Rats.

    PubMed

    Cao, Zhi-Peng; Zhang, Yuan; Mi, Li; Luo, Xin-Yi; Tian, Mei-Hui; Zhu, Bao-Li

    2016-09-01

    To investigate the patterns of B-type natriuretic peptide (BNP) expression after arrhythmia, BNP was assessed at different time points (0 minute, 10 minutes, 30 minutes, 1 hour, 3 hours, and 6 hours) in CaCl2-induced arrhythmia in rats through various methods such as immunohistochemistry, Western blotting, quantitative real-time polymerase chain reaction, and enzyme-linked immunosorbent assay. Immunohistochemistry results showed that the expression of BNP in the endocardium was higher than that in the epicardium in rats undergoing sustained arrhythmias. The BNP-to-GAPDH (glyceraldehyde-3-phosphate dehydrogenase) ratios determined by Western blotting analysis revealed no change at 0 minute but increased at 10 minutes and reached the first peak (0.48 [0.03]) at 30 minutes. After a brief decline, the second peak was observed at 6 hours (0.54 [0.03]). Similar patterns of BNP messenger RNA expression were also observed by quantitative real-time polymerase chain reaction. The plasma BNP concentrations did not change after initial bouts of cardiac arrhythmias but significantly increased 30 minutes after CaCl2 injections. The results demonstrate that arrhythmia causes an elevation of BNP in the myocardium and blood, and BNP messenger RNA increases in initial arrhythmia while its protein in myocardium and plasma does not; however, both of them were elevated after sustained arrhythmia. Such an elevated BNP expression, which is directly related to the severity and duration of the arrhythmias, may suggest the existence of fatal arrhythmia in sudden cardiac death. PMID:27258852

  1. B-type natriuretic peptide expression and cardioprotection is regulated by Akt dependent signaling at early reperfusion.

    PubMed

    Breivik, L; Jensen, A; Guvåg, S; Aarnes, E K; Aspevik, A; Helgeland, E; Hovland, S; Brattelid, T; Jonassen, A K

    2015-04-01

    Exogenously administered B-type natriuretic peptide (BNP) has been shown to offer cardioprotection through activation of particulate guanylyl cyclase (pGC), protein kinase G (PKG) and KATP channel opening. The current study explores if cardioprotection afforded by short intermittent BNP administration involves PI3K/Akt/p70s6k dependent signaling, and whether this signaling pathway may participate in regulation of BNP mRNA expression at early reperfusion. Isolated Langendorff perfused rat hearts were subjected to 30min of regional ischemia and 120min of reperfusion (IR). Applying intermittent 3×30s infusion of BNP peptide in a postconditioning like manner (BNPPost) reduced infarct size by >50% compared to controls (BNPPost 17±2% vs. control 42±4%, p<0.001). Co-treatment with inhibitors of the PI3K/Akt/p70s6k pathway (wortmannin, SH-6 and rapamycin) completely abolished the infarct-limiting effect of BNP postconditioning (BNPPost+Wi 36±5%, BNPPost+SH-6 41±4%, BNPPost+Rap 37±6% vs. BNPPost 17±2%, p<0.001). Inhibition of natriuretic peptide receptors (NPR) by isatin also abrogated BNPPost cardioprotection (BNPPost+isatin 46±2% vs. BNPPost 17±2%, p<0.001). BNPPost also significantly phosphorylated Akt and p70s6k at early reperfusion, and Akt phosphorylation was inhibited by SH-6 and isatin. Myocardial BNP mRNA levels in the area at risk (AA) were significantly elevated at early reperfusion as compared to the non-ischemic area (ANA) (Ctr(AA) 2.7±0.5 vs. Ctr(ANA) 1.2±0.2, p<0.05) and the ischemic control tissue (Ctr(AA) 2.7±0.5 vs. ischemia 1.0±0.1, p<0.05). Additional experiments also revealed a significant higher BNP mRNA level in ischemic postconditioned (IPost) hearts as compared to ischemic controls (IPost 6.7±1.3 vs. ischemia 1.0±0.2, p<0.05), but showed no difference from controls run in parallel (Ctr 5.4±0.8). Akt inhibition by SH-6 completely abrogated this elevation (IPost 6.7±1.3 vs. IPost+SH-6 1.8±0.7, p<0.05) (Ctr 5.4±0.8 vs. SH-6 1.5±0

  2. Serum 25-hydroxyvitamin D and parathyroid hormone in relation to plasma B-type natriuretic peptide: the Hoorn Study

    PubMed Central

    van Ballegooijen, Adriana J; Visser, Marjolein; Snijder, Marieke B; Dekker, Jacqueline M; Nijpels, Giel; Stehouwer, Coen D A; Diamant, Michaela; Brouwer, Ingeborg A

    2012-01-01

    Objective A disturbed vitamin D–parathyroid hormone (PTH)–calcium axis may play a role in the pathogenesis of heart failure. Therefore, we investigated whether lower 25-hydroxyvitamin D (25(OH)D) and higher PTH are cross sectionally and after 8 years of follow-up associated with higher B-type natriuretic peptide (BNP) levels in older men and women. Design and methods We measured baseline 25(OH)D, PTH, and BNP in 502 subjects in 2000–2001 in the Hoorn Study, a population-based cohort. Follow-up BNP was available in 2007–2009 in 278 subjects. Subjects were categorized according to season- and sex-specific quartiles of 25(OH)D and PTH at baseline. We studied the association of 25(OH)D and PTH quartiles with BNP using linear regression analyses adjusting for confounders. Analyses were stratified by kidney function estimated glomerular filtration rate (eGFR; ≤60 ml/min per 1.73 m2) because of significant interaction. Results At baseline, subjects had a mean age of 69.9±6.6 years, mean 25(OH)D level was 52.2±19.5 nmol/l and mean PTH 6.1±2.4 pmol/l. Cross sectionally, 25(OH)D was associated with BNP in subjects with impaired kidney function (eGFR ≤60 ml/min) only. The association attenuated after adjustment for PTH. PTH was cross sectionally associated with BNP, also in subjects with impaired kidney function only: regression coefficient of highest quartile 9.9 pmol/l (95% confidence interval 2.5, 17.4) with a significant trend across quartiles. Neither 25(OH)D nor PTH was associated with BNP in longitudinal analyses. Conclusion This study showed overall no strong association between 25(OH)D and BNP. However, PTH was associated with BNP in subjects with impaired kidney function and may point to a potential role in myocardial function. PMID:23781303

  3. Validation of a B-type natriuretic peptide as a prognostic marker in pneumonia patients: a prospective cohort study

    PubMed Central

    Usuda, Daisuke; Sangen, Ryusho; Hashimoto, Yu; Muranaka, Emiri; Iinuma, Yoshitsugu; Kanda, Tsugiyasu

    2016-01-01

    Objectives To validate a B-type natriuretic peptide (BNP) as a prognostic marker in pneumonia patients. Design A prospective cohort study. Setting Kanazawa Medical University Himi Municipal (a 250-bed community hospital in Himi-shi, Toyama-ken, Japan). Participants All patients diagnosed with pneumonia by the physician and admitted to our hospital between 1 January 2012 and 31 March 2015 whose BNP levels had been determined in the first 24 h of admission. A total of 673 patients were enrolled. Of these, BNP levels were measured for a total of 369 patients on admission. Intervention After enrolment, baseline, demographic, clinical and laboratory characteristics including levels of suspected prognostic markers for pneumonia proposed in previous papers, were collected. All patients were followed up until discharge. During analysis, they were divided into categories as follows: community-acquired pneumonia (CAP), aspiration pneumonia (AP), healthcare-associated pneumonia (HCAP) and pneumonia with acute heart failure (PAHF). A univariate and multivariable Cox-regression analysis were applied to each parameter to identify predictors of death. Three cut-off points, namely 40, 100 and 200 pg/mL, as well as the mean, were applied when comparing BNP levels. Main outcome measures 30-day mortality. Results Of the 369 patients finally included, 137 were diagnosed with CAP, 122 with AP, 74 with HCAP, and 36 with PAHF. In the univariate analysis, BNP levels (mean, cut-off points 100 pg/mL and 200 pg/mL, p<0.01, respectively) were associated with death in CAP, and similar situation was found for BNP (cut-off points 200 pg/mL, p<0.05) in AP, but not for HCAP, or PAHF. In multivariable Cox-regression analysis, BNP remained an independent mortality predictor (HR 10.01, 95% CI 1.32 to 75.7, p=0.03) in CAP. Conclusions BNP levels may be a useful single prognostic marker for CAP. Further research for validation is warranted. PMID:26908529

  4. Increased B-Type Natriuretic Peptide Concentration Is Associated with Reduced Coronary Vasoreactivity in Patients with Dilated Cardiomyopathy but Not in Healthy Young Subjects

    PubMed Central

    Sundell, Jan; Engblom, Erik; Koistinen, Juhani; Ylitalo, Antti; Laine, Hanna; Kalliokoski, Riikka; Airaksinen, K. E. Juhani; Bax, Jeroen J.; Knuuti, Juhani

    2011-01-01

    Background/Aims. Natriuretic peptides are associated with the cardiovascular disease risk under a range of different circumstances. However, less is known about whether this association is found also in young healthy subjects. Methods. 9 patients with dilated cardiomyopathy and 26 healthy young subjects were studied. The myocardial blood flow measurements were performed basally and during adenosine infusion using PET. Results. S-proBNP concentrations were significantly higher (2153 ± 1964 versus 28 ± 17 ng/L, P = .000002) and adenosine-stimulated flow lower (1.6 ± 0.8 versus 3.6 ± 1.1 mL·g−1·min−1, P = .00001) in patients with dilated cardiomyopathy when compared to healthy subjects. S-proBNP concentration was inversely associated with adenosine stimulated flow in patients with dilated cardiomyopathy (r = −0.75, P = .019) but not in healthy subjects (r = −0.06, P = .84). Conclusions. Natriuretic peptides are inversely associated with coronary vasoreactivity in patients with dilated cardiomyopathy but not in healthy young subjects. Since reduced coronary vasoreactivity seems to be one of the earliest abnormalities in the development of coronary artery disease, this might indicate that natriuretic peptides are not predictor of cardiovascular disease risk in healthy young subjects. PMID:22347648

  5. Changes in plasma levels of B-type natriuretic peptide with acute exacerbations of chronic obstructive pulmonary disease

    PubMed Central

    Nishimura, Koichi; Nishimura, Takashi; Onishi, Katsuya; Oga, Toru; Hasegawa, Yoshinori; Jones, Paul W

    2014-01-01

    Background Elevated plasma B-type natriuretic peptide (BNP) levels and their association with heart failure have been reported in subjects with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Purpose To examine and compare plasma BNP levels and diastolic and systolic dysfunction in subjects with AECOPD and stable chronic obstructive pulmonary disease (COPD). Methods In all, 87 unselected consecutive hospitalizations due to AECOPD in 61 subjects and a total of 190 consecutive subjects with stable COPD were recruited. Plasma BNP levels were compared cross-sectionally and longitudinally. Transthoracic echocardiographic examinations were also performed in the hospitalized subjects. Results In the hospitalized subjects, the median plasma BNP level (interquartile range) was 55.4 (26.9–129.3) pg/mL and was higher than that of patients with stable COPD: 18.3 (10.0–45.3) for Global Initiative for Chronic Obstructive Lung Disease grade I; 25.8 (11.0–53.7) for grade II; 22.1 (9.1–52.6) for grade III; and 17.2 (9.6–22.9) pg/mL for grade I V, all P<0.001. In 15 subjects studied prospectively, the median plasma BNP level was 19.4 (9.8–32.2) pg/mL before AECOPD, 72.7 (27.7–146.3) pg/mL during AECOPD, and 14.6 (12.9–39.0) pg/mL after AECOPD (P<0.0033 and P<0.0013, respectively). Median plasma BNP levels during AECOPD were significantly higher in ten unsuccessfully discharged subjects 260.5 (59.4–555.0) than in 48 successfully discharged subjects 48.5 (24.2–104.0) pg/mL (P=0.0066). Only 5.6% of AECOPD subjects were associated with systolic dysfunction defined as a left ventricular ejection fraction (LVEF) <50%; a further 7.4% were considered to have impaired relaxation defined as an E/A wave velocity ratio <0.8 and a deceleration time of E >240 ms. BNP levels were weakly correlated with the E/peak early diastolic velocity of the mitral annulus (Ea) ratio (Spearman’s rank correlation coefficient =0.353, P=0.018), but they were not

  6. B-Type Natriuretic Peptide-Induced Delayed Modulation of TRPV1 and P2X3 Receptors of Mouse Trigeminal Sensory Neurons

    PubMed Central

    Ntamati, Niels; Nistri, Andrea

    2013-01-01

    Important pain transducers of noxious stimuli are small- and medium-diameter sensory neurons that express transient receptor vanilloid-1 (TRPV1) channels and/or adenosine triphosphate (ATP)-gated P2X3 receptors whose activity is upregulated by endogenous neuropeptides in acute and chronic pain models. Little is known about the role of endogenous modulators in restraining the expression and function of TRPV1 and P2X3 receptors. In dorsal root ganglia, evidence supports the involvement of the natriuretic peptide system in the modulation of nociceptive transmission especially via the B-type natriuretic peptide (BNP) that activates the natriuretic peptide receptor-A (NPR-A) to downregulate sensory neuron excitability. Since the role of BNP in trigeminal ganglia (TG) is unclear, we investigated the expression of BNP in mouse TG in situ or in primary cultures and its effect on P2X3 and TRPV1 receptors of patch-clamped cultured neurons. Against scant expression of BNP, almost all neurons expressed NPR-A at membrane level. While BNP rapidly increased cGMP production and Akt kinase phosphorylation, there was no early change in passive neuronal properties or responses to capsaicin, α,β-meATP or GABA. Nonetheless, 24 h application of BNP depressed TRPV1 mediated currents (an effect blocked by the NPR-A antagonist anantin) without changing responses to α,β-meATP or GABA. Anantin alone decreased basal cGMP production and enhanced control α,β-meATP-evoked responses, implying constitutive regulation of P2X3 receptors by ambient BNP. These data suggest a slow modulatory action by BNP on TRPV1 and P2X3 receptors outlining the role of this peptide as a negative regulator of trigeminal sensory neuron excitability to nociceptive stimuli. PMID:24312267

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

    PubMed Central

    Rasmussen, Kirsten C; Højskov, Michael; Ruhnau, Birgitte; Salling, Lisbeth; Pedersen, Tom; Goetze, Jens P; Secher, Niels H

    2016-01-01

    Objectives During 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 fluid balance. Design Prospective observational study. Setting One university/tertiary centre. Participants The study included patients who underwent radical cystectomy. Plasma for determination of proANP was obtained before surgery, after resection of the bladder, and at the end of surgery for 20 robotic-assisted radical cystectomy (RARC) and 20 open radical cystectomy (ORC) procedures. Results The blood loss was 1871 (95% CI 1267 to 2475) vs 589 mL (378 to 801) in the ORC and RARC groups (p=0.001), respectively, and fluid balance was positive by 1518 mL (1215 to 1821) during ORC, and by 1858 mL (1461 to 2255) during RARC (p=0.163). Yet, at the end of ORC, plasma proANP was reduced by 23% (14% to 32%, p=0.001), while plasma proANP did not change significantly during RARC. Thus, plasma proANP was associated both with the perioperative blood loss (r= −0.475 (0.632 to −0.101), p=0.002), and with fluid balance (r=0.561 (0.302 to 0.740), p=0.001), indicating that a stable plasma proANP required a fluid surplus by 2.4 L (2.0 to 2.7). Conclusions There was a correlation between intraoperative haemorrhage and a decrease in plasma proANP and, taking plasma proANP to indicate filling of the heart, about 2.5 L surplus volume of lactated Ringer's solution appears to maintain cardiac preload during cystectomy. Trial registration number EudraCT (2012-005040-20), Results. PMID:26908528

  8. B-type natriuretic peptide (BNP), not ANP, is the principal cardiac natriuretic peptide in vertebrates as revealed by comparative studies.

    PubMed

    Takei, Yoshio; Inoue, Koji; Trajanovska, Sofie; Donald, John A

    2011-05-01

    The natriuretic peptide (NP) family consists of at least seven members; cardiac ANP, BNP and VNP and brain CNPs (CNP1-4). Phylogenetic and comparative genomic analyses showed that CNP4 is the ancestral molecule of the family, from which CNP3 and CNP1/2 were duplicated in this order, and that the three cardiac NPs were generated from CNP3 by tandem duplication. Seven members existed at the divergence of ray-finned fishes and lobe-finned fishes (tetrapods), but some of the NP genes have disappeared during the course of evolution. In ray-finned fishes, all three cardiac NPs exist in chondrostei and some migratory teleost species, but VNP is generally absent and ANP is absent in a group of teleosts (Beloniformes). In tetrapods, ANP and BNP are present in mammals and amphibians, but ANP is usually absent in reptiles and birds. Thus, BNP is a ubiquitous cardiac NP in bony fishes and tetrapods though elasmobranchs and cyclostomes have only CNP3/4 as a cardiac NP. Functional studies indicate that cardiac NPs are essential Na(+)-extruding hormones throughout vertebrates; they play critical roles in seawater (SW) adaptation in teleosts, while they are important volume-depleting hormones in mammals as water and Na(+) are regulated in parallel in terrestrial animals. In mammals, cardiac NPs become prominent in pathological conditions such as heart failure where they are used in diagnosis and treatment. Although the functional role of BNP has not yet been fully elucidated compared with ANP in non-mammalian vertebrates, it appears that BNP plays pivotal roles in the cardiovascular and body fluid regulation as shown in mammals. ANP has previously been recognized as the principal cardiac NP in mammals and teleosts, but comparative studies have revealed that BNP is the only cardiac NP that exists in all tetrapods and teleosts. This is an excellent example showing that comparative studies have created new insights into the molecular and functional evolution of a hormone family. PMID

  9. Binding and aggregation of pro-atrial natriuretic factor by calcium.

    PubMed

    Thibault, G; Doubell, A F

    1992-04-01

    Analysis of atrial secretory granule content by sodium dodecyl sulfate-gel electrophoresis followed by a 45Ca2+ overlay assay indicates that a 17,000 protein binds 45Ca2+. This protein, which can be immunostained by atrial natriuretic factor (ANF) antiserum, corresponds to proANF. Ca2+ binding is proportional to the amount of proANF and pH dependent. Generation of ANF-(1-98) by thrombin digestion of proANF does not affect Ca2+ binding. Blocking the carboxyl groups of proANF and the use of NH2-terminal fragments bearing those carboxyl groups demonstrated that the Ca(2+)-interaction site is probably located within the highly acidic portion (11-30) of the propeptide. Ca2+ binding to proANF induces its aggregation that can be verified by sedimentation. ProANF aggregation is Ca2+ dependent, being optimal at 10 mM, partially pH dependent, and greatly increased by high concentrations of proANF. However, because of its relatively low-binding affinity, Ca2+ can be substituted by other divalent cations such as Sr2+, Ba2+, or Mg2+. The high level of Ca2+ in atrial secretory granules and the aggregation of proANF in the presence of Ca2+ suggest a possible involvement of these physicochemical properties in the condensed state of the matrix of secretory granules. Indeed, detergent solubilization of the membrane of the secretory granules in presence of Ca2+ resulted only in a partial dissolution of the dense core matrix. We therefore postulate that, in the Golgi complex, proANF and Ca2+ associate to form a condensed aggregate that helps package secretory material into secretory vesicles. PMID:1533094

  10. Comparison of B-type natriuretic peptide and left ventricular dysfunction in patients with constrictive pericarditis undergoing pericardiectomy.

    PubMed

    Kapoor, Poonam Malhotra; Aggarwal, Vikram; Chowdhury, Ujjwal; Choudhury, Minati; Singh, Sarvesh Pal; Kiran, Usha

    2010-01-01

    Chronic constrictive pericarditis (CCP) due to tuberculosis has high morbidity and mortality in the periopeartive period following pericardiectomy because of left ventricular (LV) dysfunction. Brain-type natriuretic peptide (BNP) is considered a marker for both LV systolic and diastolic dysfunction. We undertook this prospective study in 24 patients, to measure the BNP levels and to compare it with transmitral Doppler flow velocities, that is, the E/A ratio (E = initial peak velocity during early diastolic filling and A = late peak flow velocity during atrial systole), as a marker of diastolic function and systolic parameters, pre- and post-pericardiectomy, at the time of discharge. The latter parameters have been taken as a flow velocity across the mitral valve on a transthoracic echo. There was a significant decrease in the mean values of log BNP (6.19 +/- 0.33 to 4.65 +/- 0.14) (P = 0.001) and E/A ratio (1.81 +/- 0.21 to 1.01 +/- 0.14) (P = 0.001) post pericardiectomy, with a positive correlation, r = 0.896 and 0.837, respectively, between the two values at both the time periods. There was significant improvement in the systolic parameters of the LV function, that is, stroke volume index, cardiac index, systemic vascular resistance index, and delivered oxygen index. However, no correlation was observed between these values and the BNP levels. We believe that BNP can be used as a marker for LV diastolic dysfunction in place of the E/A ratio in patients with CCP, undergoing pericardiectomy. However, more studies have to be performed for validation of the same. PMID:20442542

  11. Ranolazine attenuated heightened plasma norepinephrine and B-Type natriuretic peptide-45 in improving cardiac function in rats with chronic ischemic heart failure.

    PubMed

    Feng, Guangqiu; Yang, Yu; Chen, Juan; Wu, Zhiyong; Zheng, Yin; Li, Wei; Dai, Wenxin; Guan, Pin; Zhong, Chunrong

    2016-01-01

    As a new anti-anginal agent, ranolazinehas been shown to play a cardioprotective role in regulating myocardial ischemic injury. Given that plasma norepinephrine (NE) and brain natriuretic peptide (BNP, also termed B-type natriuretic peptide-45 in rats) are considered neuron-hormones to indicate heart failure progression. This study aims to examine effects of ranolazine on plasma NE and BNP-45 of rats with chronic ischemic heart failure (CHF). CHF was induced by myocardial infarction following ligation of a left anterior descending artery in adult Sprague-Dawley rats. We hypothesized that ranolazine attenuates the elevated levels of NE and BNP-45 observed in CHF rats thereby leading to improvement of the left ventricular function. Results showed that levels of plasma NE and BNP-45 were increased in CHF rats 6-8 weeks after ligation of the coronary artery. Our data demonstrate for the first time that ranolazine significantly attenuated the augmented NE and BNP-45 induced by CHF (P<0.05 vs. saline control). In addition, a liner relation was observed between NE/BNP-45levels and left ventricular fractional shortening as indication of left ventricular function (r=0.91 and P<0.01 for NE; and r=0.93 and P<0.01 for BNP-45) after administration of ranolazine. In conclusion, CHF increases the expression of NE and BNP-45 in peripheral circulation and these changes are related to the left ventricular function. Ranolazine improves the left ventricular function likely by decreasing heightened NE and BNP-45 induced by CHF. Therefore, our data indicate the role played by ranolazine in improving cardiac function in rats with CHF. PMID:27158417

  12. Ranolazine attenuated heightened plasma norepinephrine and B-Type natriuretic peptide-45 in improving cardiac function in rats with chronic ischemic heart failure

    PubMed Central

    Feng, Guangqiu; Yang, Yu; Chen, Juan; Wu, Zhiyong; Zheng, Yin; Li, Wei; Dai, Wenxin; Guan, Pin; Zhong, Chunrong

    2016-01-01

    As a new anti-anginal agent, ranolazinehas been shown to play a cardioprotective role in regulating myocardial ischemic injury. Given that plasma norepinephrine (NE) and brain natriuretic peptide (BNP, also termed B-type natriuretic peptide-45 in rats) are considered neuron-hormones to indicate heart failure progression. This study aims to examine effects of ranolazine on plasma NE and BNP-45 of rats with chronic ischemic heart failure (CHF). CHF was induced by myocardial infarction following ligation of a left anterior descending artery in adult Sprague-Dawley rats. We hypothesized that ranolazine attenuates the elevated levels of NE and BNP-45 observed in CHF rats thereby leading to improvement of the left ventricular function. Results showed that levels of plasma NE and BNP-45 were increased in CHF rats 6-8 weeks after ligation of the coronary artery. Our data demonstrate for the first time that ranolazine significantly attenuated the augmented NE and BNP-45 induced by CHF (P<0.05 vs. saline control). In addition, a liner relation was observed between NE/BNP-45levels and left ventricular fractional shortening as indication of left ventricular function (r=0.91 and P<0.01 for NE; and r=0.93 and P<0.01 for BNP-45) after administration of ranolazine. In conclusion, CHF increases the expression of NE and BNP-45 in peripheral circulation and these changes are related to the left ventricular function. Ranolazine improves the left ventricular function likely by decreasing heightened NE and BNP-45 induced by CHF. Therefore, our data indicate the role played by ranolazine in improving cardiac function in rats with CHF. PMID:27158417

  13. Spinal Functions of B-Type Natriuretic Peptide, Gastrin-Releasing Peptide, and Their Cognate Receptors for Regulating Itch in Mice

    PubMed Central

    Kiguchi, Norikazu; Sukhtankar, Devki D.; Ding, Huiping; Tanaka, Ken-ichi; Kishioka, Shiroh; Peters, Christopher M.

    2016-01-01

    B-type natriuretic peptide (BNP)–natriuretic peptide receptor A (NPRA) and gastrin-releasing peptide (GRP)–GRP receptor (GRPR) systems contribute to spinal processing of itch. However, pharmacological and anatomic evidence of these two spinal ligand-receptor systems are still not clear. The aim of this study was to determine the spinal functions of BNP-NPRA and GRP-GRPR systems for regulating scratching activities in mice by using pharmacological and immunohistochemical approaches. Our results showed that intrathecal administration of BNP (0.3–3 nmol) dose dependently elicited scratching responses, which could be blocked by the NPRA antagonist (Arg6,β-cyclohexyl-Ala8,D-Tic16,Arg17,Cys18)-atrial natriuretic factor(6-18) amide (A71915). However, A71915 had no effect on intrathecal GRP-induced scratching. In contrast, pretreatment with a GRPR antagonist (D-Tpi6,Leu13ψ(CH2-NH)-Leu14)bombesin(6-14) (RC-3095) inhibited BNP-induced scratching. Immunostaining revealed that NPRA proteins colocalize with GRP, but not GRPR, in the superficial area of dorsal horn, whereas BNP proteins do not colocalize with either GRP or GRPR in the dorsal horn. Intradermal administration of ligands including endothelin-1, U-46619, bovine adrenal medulla 8-22, and Ser-Leu-Ile-Gly-Arg-Leu-NH2 (SLIGRL) increased scratching bouts at different levels of magnitude. Pretreatment with intrathecal A71915 did not affect scratching responses elicited by all four pruritogens, whereas pretreatment with RC-3095 only inhibited SLIGRL-induced scratching. Interestingly, immunostaining showed that RC-3095, but not A71915, inhibited SLIGRL-elicited c-Fos activation in the spinal dorsal horn, which was in line with behavioral outcomes. These findings demonstrate that: 1) BNP-NPRA system may function upstream of the GRP-GRPR system to regulate itch in the mouse spinal cord, and 2) both NPRA and GRPR antagonists may have antipruritic efficacy against centrally, but not peripherally, elicited itch. PMID

  14. Spinal Functions of B-Type Natriuretic Peptide, Gastrin-Releasing Peptide, and Their Cognate Receptors for Regulating Itch in Mice.

    PubMed

    Kiguchi, Norikazu; Sukhtankar, Devki D; Ding, Huiping; Tanaka, Ken-ichi; Kishioka, Shiroh; Peters, Christopher M; Ko, Mei-Chuan

    2016-03-01

    B-type natriuretic peptide (BNP)-natriuretic peptide receptor A (NPRA) and gastrin-releasing peptide (GRP)-GRP receptor (GRPR) systems contribute to spinal processing of itch. However, pharmacological and anatomic evidence of these two spinal ligand-receptor systems are still not clear. The aim of this study was to determine the spinal functions of BNP-NPRA and GRP-GRPR systems for regulating scratching activities in mice by using pharmacological and immunohistochemical approaches. Our results showed that intrathecal administration of BNP (0.3-3 nmol) dose dependently elicited scratching responses, which could be blocked by the NPRA antagonist (Arg6,β-cyclohexyl-Ala8,D-Tic16,Arg17,Cys18)-atrial natriuretic factor(6-18) amide (A71915). However, A71915 had no effect on intrathecal GRP-induced scratching. In contrast, pretreatment with a GRPR antagonist (D-Tpi6,Leu13ψ(CH2-NH)-Leu14)bombesin(6-14) (RC-3095) inhibited BNP-induced scratching. Immunostaining revealed that NPRA proteins colocalize with GRP, but not GRPR, in the superficial area of dorsal horn, whereas BNP proteins do not colocalize with either GRP or GRPR in the dorsal horn. Intradermal administration of ligands including endothelin-1, U-46619, bovine adrenal medulla 8-22, and Ser-Leu-Ile-Gly-Arg-Leu-NH2 (SLIGRL) increased scratching bouts at different levels of magnitude. Pretreatment with intrathecal A71915 did not affect scratching responses elicited by all four pruritogens, whereas pretreatment with RC-3095 only inhibited SLIGRL-induced scratching. Interestingly, immunostaining showed that RC-3095, but not A71915, inhibited SLIGRL-elicited c-Fos activation in the spinal dorsal horn, which was in line with behavioral outcomes. These findings demonstrate that: 1) BNP-NPRA system may function upstream of the GRP-GRPR system to regulate itch in the mouse spinal cord, and 2) both NPRA and GRPR antagonists may have antipruritic efficacy against centrally, but not peripherally, elicited itch. PMID:26669425

  15. Differential expression of the pro-natriuretic peptide convertases corin and furin in experimental heart failure and atrial fibrosis

    PubMed Central

    Boerrigter, Guido; Huntley, Brenda K.; Sangaralingham, S. Jeson; McKie, Paul M.; Harty, Gail J.; Harders, Gerald E.; Burnett, John C.

    2013-01-01

    In heart failure (HF), the cardiac hormone natriuretic peptides (NPs) atrial (ANP), B-type (BNP), and C-type (CNP) play a key role to protect cardiac remodeling. The proprotein convertases corin and furin process their respective pro-NPs into active NPs. Here we define in a canine model of HF furin and corin gene and protein expression in normal and failing left atrium (LA) or ventricle (LV) testing the hypothesis that the NP proproteins convertases production is altered in experimental HF. Experimental canine HF was produced by rapid right ventricular pacing for 10 days. NPs, furin, and corin mRNA expression were determined by quantitative RT-PCR. Protein concentration or expression was determined by immunostaining, radioimmunoassay, or Western blot. Furin and corin proteins were present in normal canine LA and LV myocardium and vasculature and in smooth muscle cells. In normal canines, expression of NPs was dominant in the atrium compared with the ventricle. In experimental early stage HF characterized with marked atrial fibrosis, ANP, BNP, and CNP mRNA, and protein concentrations were higher in HF LA but not HF LV compared with normals. In LA, corin mRNA and protein expressions in HF were lower, whereas furin mRNA and protein expressions were higher than normals. NPs and furin expressions were augmented in the atrium in experimental early stage HF and, conversely, corin mRNA and protein expressions were decreased with atrial remodeling. Selective changes of these NP convertases may have significance in the regulation of pro-NP processing and atrial remodeling in early stage HF. PMID:23152112

  16. Role of galectin-3 and plasma B type-natriuretic peptide in predicting prognosis in discharged chronic heart failure patients.

    PubMed

    Feola, Mauro; Testa, Marzia; Leto, Laura; Cardone, Marco; Sola, Mario; Rosso, Gian Luca

    2016-06-01

    Galectin-3 demonstrated to be a robust independent marker of cardiovascular mid-term (18-month) outcome in heart failure (HF) patients. The objective of this study was to analyze the value of a predischarged determination of plasma galectin-3 alone and with plasma brain natriuretic peptide (BNP) in predicting mid-term outcome in frequent-flyers (FF) HF (≥2 hospitalization for HF/year)/dead patients discharged after an acute decompensated HF (ADHF) episode.All FF chronic HF subjects discharged alive after an ADHF were enrolled. All patients underwent a determination of BNP and galectin-3, a 6-minute walk test, and an echocardiogram within 48 hours upon hospital discharge. Death by any cause, cardiac transplantation, and worsening HF requiring readmission to hospital were considered cardiovascular events.Eighty-three patients (67 males, age 73.2 ± 8.6 years old) were analyzed (mean follow-up 11.6 ± 5.2 months; range 4-22 months). During the follow-up 38 events (45.7%) were scheduled: (13 cardiac deaths, 35 rehospitalizations for ADHF). According to medical history, in 33 patients (39.8%) a definition of FF HF patients was performed (range 2-4 hospitalization/year). HF patients who suffered an event (FF or death) demonstrated more impaired ventricular function (P = 0.037), higher plasma BNP (P = 0.005), and Gal-3 at predischarge evaluation (P = 0.027). Choosing adequate cut-off points (BNP ≥ 500 pg/mL and Gal-3 ≥ 17.6 ng/mL), the Kaplan-Meier curves depicted the powerful stratification using BNP + Gal-3 in predicting clinical course at mid-term follow-up (log rank 5.65; P = 0.017).Adding Gal-3 to BNP, a single predischarge strategy testing seemed to obtain a satisfactorily predictive value in alive HF patients discharged after an ADHF episode. PMID:27368017

  17. Role of galectin-3 and plasma B type-natriuretic peptide in predicting prognosis in discharged chronic heart failure patients

    PubMed Central

    Feola, Mauro; Testa, Marzia; Leto, Laura; Cardone, Marco; Sola, Mario; Rosso, Gian Luca

    2016-01-01

    Abstract Galectin-3 demonstrated to be a robust independent marker of cardiovascular mid-term (18-month) outcome in heart failure (HF) patients. The objective of this study was to analyze the value of a predischarged determination of plasma galectin-3 alone and with plasma brain natriuretic peptide (BNP) in predicting mid-term outcome in frequent-flyers (FF) HF (≥2 hospitalization for HF/year)/dead patients discharged after an acute decompensated HF (ADHF) episode. All FF chronic HF subjects discharged alive after an ADHF were enrolled. All patients underwent a determination of BNP and galectin-3, a 6-minute walk test, and an echocardiogram within 48 hours upon hospital discharge. Death by any cause, cardiac transplantation, and worsening HF requiring readmission to hospital were considered cardiovascular events. Eighty-three patients (67 males, age 73.2 ± 8.6 years old) were analyzed (mean follow-up 11.6 ± 5.2 months; range 4–22 months). During the follow-up 38 events (45.7%) were scheduled: (13 cardiac deaths, 35 rehospitalizations for ADHF). According to medical history, in 33 patients (39.8%) a definition of FF HF patients was performed (range 2–4 hospitalization/year). HF patients who suffered an event (FF or death) demonstrated more impaired ventricular function (P = 0.037), higher plasma BNP (P = 0.005), and Gal-3 at predischarge evaluation (P = 0.027). Choosing adequate cut-off points (BNP ≥ 500 pg/mL and Gal-3 ≥ 17.6 ng/mL), the Kaplan–Meier curves depicted the powerful stratification using BNP + Gal-3 in predicting clinical course at mid-term follow-up (log rank 5.65; P = 0.017). Adding Gal-3 to BNP, a single predischarge strategy testing seemed to obtain a satisfactorily predictive value in alive HF patients discharged after an ADHF episode. PMID:27368017

  18. Age-adjusted plasma N-terminal pro-brain natriuretic peptide level in Kawasaki disease

    PubMed Central

    Jun, Heul; Ko, Kyung Ok; Lim, Jae Woo; Yoon, Jung Min; Lee, Gyung Min

    2016-01-01

    Purpose Recent reports showed that plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) could be a useful biomarker of intravenous immunoglobulin (IVIG) unresponsiveness and coronary artery lesion (CAL) development in Kawasaki disease (KD). The levels of these peptides are critically influenced by age; hence, the normal range and upper limits for infants and children are different. We performed an age-adjusted analysis of plasma NT-proBNP level to validate its clinical use in the diagnosis of KD. Methods The data of 131 patients with KD were retrospectively analyzed. The patients were divided into 2 groups—group I (high NT-proBNP group) and group II (normal NT-proBNP group)—comprising patients with NT-proBNP concentrations higher and lower than the 95th percentile of the reference value, respectively. We compared the laboratory data, responsiveness to IVIG, and the risk of CAL in both groups. Results Group I showed significantly higher white blood cell count, absolute neutrophil count, C-reactive protein level, aspartate aminotransferase level, and troponin-I level than group II (P<0.05). The risk of CAL was also significantly higher in group I (odds ratio, 5.78; P=0.012). IVIG unresponsiveness in group I was three times that in group II (odds ratio, 3.35; P= 0.005). Conclusion Age-adjusted analysis of plasma NT-proBNP level could be helpful in predicting IVIG unresponsiveness and risk of CAL development in patients with KD. PMID:27588030

  19. Increase in plasma concentrations of cardiodilatin (amino terminal pro-atrial natriuretic peptide) in cardiac failure and during recumbency.

    PubMed Central

    Meleagros, L; Gibbs, J S; Ghatei, M A; Bloom, S R

    1988-01-01

    Plasma concentrations of cardiodilatin, the peptide sequence at the amino terminal of the pro-atrial natriuretic peptide, in 17 normal subjects ranged from 59 to 202 (mean 118 (SEM) (9] pmol/l. Recumbency increased the mean (SEM) concentration to 160 (13) pmol/l. The plasma concentration of cardiodilatin in 24 patients with congestive cardiac failure was much higher (964 (175) pmol/l) than in the normal subjects. It was highest in those with heart failure in New York Heart Association functional classes III and IV and the concentration correlated both with atrial natriuretic peptide concentrations and left ventricular ejection fraction. Concentrations rose during induced tachycardia in three patients tested. Chromatography showed a single clean peak of plasma cardiodilatin immunoreactivity. It seems that cardiodilatin is a second circulating cardiac peptide that is jointly released with atrial natriuretic peptide by common stimuli. Other workers have reported that, like atrial natriuretic peptide, three partial cardiodilatin sequences can stimulate renal particulate guanylate cyclase and increase cyclic guanosine monophosphate. The simultaneous release of cardiodilatin in higher circulating concentrations than atrial natriuretic peptide may be relevant to the finding that appropriate concentrations of exogenous atrial natiuretic peptide alone do not produce the full renal effects associated with endogenous peptide release. PMID:2970269

  20. Short-term add-on therapy with angiotensin receptor blocker for end-stage inotrope-dependent heart failure patients: B-type natriuretic peptide reduction in a randomized clinical trial

    PubMed Central

    Ochiai, Marcelo E; Brancalhão, Euler C O; Puig, Raphael S. N.; Vieira, Kelly R N; Cardoso, Juliano N; de Oliveira-Jr, Múcio Tavares; Barretto, Antonio C P

    2014-01-01

    OBJECTIVE: We aimed to evaluate angiotensin receptor blocker add-on therapy in patients with low cardiac output during decompensated heart failure. METHODS: We selected patients with decompensated heart failure, low cardiac output, dobutamine dependence, and an ejection fraction <0.45 who were receiving an angiotensin-converting enzyme inhibitor. The patients were randomized to losartan or placebo and underwent invasive hemodynamic and B-type natriuretic peptide measurements at baseline and on the seventh day after intervention. ClinicalTrials.gov: NCT01857999. RESULTS: We studied 10 patients in the losartan group and 11 patients in the placebo group. The patient characteristics were as follows: age 52.7 years, ejection fraction 21.3%, dobutamine infusion 8.5 mcg/kg.min, indexed systemic vascular resistance 1918.0 dynes.sec/cm5.m2, cardiac index 2.8 L/min.m2, and B-type natriuretic peptide 1,403 pg/mL. After 7 days of intervention, there was a 37.4% reduction in the B-type natriuretic peptide levels in the losartan group compared with an 11.9% increase in the placebo group (mean difference, -49.1%; 95% confidence interval: -88.1 to -9.8%, p = 0.018). No significant difference was observed in the hemodynamic measurements. CONCLUSION: Short-term add-on therapy with losartan reduced B-type natriuretic peptide levels in patients hospitalized for decompensated severe heart failure and low cardiac output with inotrope dependence. PMID:24838894

  1. Amino-terminal pro-brain natriuretic peptide in children with latent rheumatic heart disease

    PubMed Central

    Zachariah, Justin P; Aliku, Twalib; Scheel, Amy; Hasan, Babar S; Lwabi, Peter; Sable, Craig; Beaton, Andrea Z

    2016-01-01

    Background: Rheumatic heart disease (RHD) is a global cause of early heart failure. Early RHD is characterized by valvar regurgitation, leading to ventricular distention and possible elaboration of amino-terminal pro-brain natriuretic peptide (NT-proBNP). We investigated the ability of NT-proBNP to distinguish cases of latent RHD detected by echocardiographic screening from the controls. Materials and Methods: Ugandan children (N = 44, 36% males, mean age: 12 ± 2 years) with latent RHD (cases) and siblings (controls) by echocardiography were enrolled. Cases and controls were matched for age and sex, and they had normal hemoglobin (mean: 12.8 mg/dL). Children with congenital heart disease, pregnancy, left ventricular dilation or ejection fraction (EF) below 55%, or other acute or known chronic health conditions were excluded. RHD cases were defined by the World Heart Federation (WHF) 2012 consensus guideline criteria as definite. Controls had no echocardiography (echo) evidence for RHD. At the time of echo, venous blood samples were drawn and stored as serum. NT-proBNP levels were measured using sandwich immunoassay. Paired t-tests were used to compare NT-proBNP concentrations including sex-specific analyses. Results: The mean NT-proBNP concentration in the cases was 105.74 ± 67.21 pg/mL while in the controls, it was 86.63 ± 55.77 pg/mL. The cases did not differ from the controls (P = 0.3). In sex-specific analyses, male cases differed significantly from the controls (158.78 ± 68.82 versus 76 ± 42.43, P = 0.008). Female cases did not differ from the controls (75.44 ± 45.03 versus 92.30 ± 62.35 respectively, P = 0.4). Conclusion: Serum NT-proBNP did not distinguish between latent RHD cases and the controls. Sex and within-family exposures may confound this result. More investigation into biomarker-based RHD detection is warranted. PMID:27212845

  2. Association of Serum Triiodothyronine with B-type Natriuretic Peptide and Severe Left Ventricular Diastolic Dysfunction in Heart Failure with Preserved Ejection Fraction

    PubMed Central

    Selvaraj, Senthil; Klein, Irwin; Danzi, Sara; Akhter, Nausheen; Bonow, Robert O.; Shah, Sanjiv J.

    2012-01-01

    There are well-documented changes in thyroid hormone metabolism that accompany heart failure (HF). However, the frequency of thyroid hormone abnormalities in HF with preserved ejection fraction (HFpEF) is unknown, and no studies have investigated the association between triiodothyronine (T3) and markers of HF severity (B-type natriuretic peptide [BNP] and diastolic dysfunction [DD]) in HFpEF. We prospectively studied 89consecutive patients with HFpEF, defined as symptomatic HF with LV ejection fraction >50% and LV end-diastolic volume index < 97 ml/m2. Patients were dichotomized into two groups based upon median T3 levels, and clinical, laboratory, and echocardiographic data were compared between groups. Univariable and multivariable linear regression analyses were performed to determine whether BNP and DD were independently associated with T3 level. We found that 22% of HFpEF patients had reduced T3. Patients with lowerT3 levels were older, more symptomatic, more frequently had hyperlipidemia and diabetes, and had higher BNP levels. Severe (grade 3) DD, higher mitral E velocity, shorter deceleration time, and higher pulse pressure/stroke volume ratio were all associated with lower T3 levels. T3 was inversely associated with both log BNP (p=0.004) and severity of DD (p=0.039). On multivariable analysis, T3 was independently associated with both log BNP (β=−4.7 [95% CI −9.0, −0.41]ng/dl, p=0.032) and severe DD (β=−16.3 [95% CI −30.1, −2.5]ng/dl, p=0.022). In conclusion, T3 is inversely associated with markers of HFpEF severity (BNP and DD). Whether reduced T3 contributes to or is a consequence of increased severity of HFpEF remains to be determined. PMID:22502900

  3. Prevalence, Clinical Phenotype, and Outcomes Associated with Normal B-Type Natriuretic Peptide Levels in Heart Failure with Preserved Ejection Fraction

    PubMed Central

    Anjan, Venkatesh Y.; Loftus, Timothy M.; Burke, Michael A.; Akhter, Nausheen; Fonarow, Gregg C.; Gheorghiade, Mihai; Shah, Sanjiv J.

    2012-01-01

    B-type natriuretic peptide (BNP) is used widely to exclude heart failure (HF) in patients with dyspnea. However, most studies of BNP have focused on diagnosing HF with reduced ejection fraction (EF). We hypothesized that a normal BNP (≤ 100 pg/ml) is relatively common in HF with preserved EF (HFpEF), a heterogeneous disorder commonly associated with obesity. We prospectively studied 159 consecutive patients enrolled in the Northwestern University HFpEF Program. All subjects had symptomatic HF with EF>50% and elevated pulmonary capillary wedge pressure (PCWP). BNP was tested at baseline in all subjects. We compared clinical characteristics, echocardiographic parameters, invasive hemodynamics, and outcomes among HFpEF patients with normal (≤ 100 pg/ml) vs. elevated (>100 pg/ml) BNP. Of the 159 HFpEF patients, 46 (29%) had BNP ≤ 100 pg/ml. Subjects with normal BNP were younger, more often female, had higher rates of obesity and higher body-mass index, and less commonly had chronic kidney disease and atrial fibrillation. Both EF and PCWP were similar in normal vs. elevated BNP groups (62±7 vs. 61±7% [P=0.67] and 25±8 vs. 27±9 mmHg [P=0.42], respectively). Elevated BNP was associated with enlarged left atrial volume, worse diastolic function, abnormal right ventricular structure/function, and worse outcomes (e.g., adjusted hazard ratio for HF hospitalization = 4.0, 95% confidence interval 1.6-9.7, P=0.003). In conclusion, a normal BNP is present in 29% of symptomatic outpatients with HFpEF who have elevated PCWP, obesity is likely the primary driver of this finding, and although BNP is useful as a prognostic marker in HFpEF, a normal BNP does not exclude the outpatient diagnosis of HFpEF. PMID:22681864

  4. Plasma B-type natriuretic peptide levels are poorly related to the occurrence of ischemia or ventricular arrhythmias during symptom-limited exercise in low-risk patients

    PubMed Central

    Porta, Andreu; Candell-Riera, Jaume; Agulló, Luis; Aguadé-Bruix, Santiago; de León, Gustavo; Figueras, Jaume; Garcia-Dorado, David

    2016-01-01

    Introduction The usefulness of B-type natriuretic peptide (BNP) as a marker of ischemia is controversial. BNP levels have predicted arrhythmias in various settings, but it is unknown whether they are related to exercise-induced ischemic ventricular arrhythmias. Material and methods We analyzed in 63 patients (64 ±14 years, 65% male, 62% with known coronary disease) undergoing exercise stress single-photon emission computed tomography (SPECT) the association between plasma BNP values (before and 15 min after exercise) and the occurrence of ischemia or ventricular arrhythmias during the test. Results Exercise test (8.1 ±2.7 min, 7.4 ±8.1 metabolic equivalents, 82 ±12% of maximal predicted heart rate) induced reversible perfusion defects in 23 (36%) patients. Eight (13%) patients presented significant arrhythmias (≥ 7 ventricular premature complexes/min, couplets, or non-sustained ventricular tachycardia during exercise or in the first minute of recovery). Median baseline BNP levels were 17.5 (12.4–66.4) pg/ml in patients developing scintigraphic ischemia and 45.6 (13.2–107.4) pg/ml in those without ischemia (p = 0.137). The BNP levels increased after exercise (34.4 (15.3–65.4)% increment over baseline, p < 0.001), but the magnitude of this increase was not related to SPECT positivity (35.7 (18.8–65.4)% vs. 27.9 (5.6–64.0)% in patients with and without ischemia, respectively, p = 0.304). No significant association was found between BNP values (at baseline or their change during the test) and ventricular arrhythmias. Conclusions Plasma BNP values – at baseline or after exercise – were not associated with myocardial ischemia or with ventricular arrhythmia during exercise SPECT. These results highlight the limited usefulness of this biomarker to assess acute ischemia. PMID:27186178

  5. Muscle mass, visceral fat, and plasma levels of B-type natriuretic peptide in healthy individuals (from the J-SHIPP Study).

    PubMed

    Yamashita, Taiji; Kohara, Katsuhiko; Tabara, Yasuharu; Ochi, Masayuki; Nagai, Tokihisa; Okada, Yoko; Igase, Michiya; Miki, Tetsuro

    2014-08-15

    A paradoxical negative association between obesity and the plasma B-type natriuretic peptide (BNP) level has been firmly established. An individual's fat mass increases and muscle mass decreases with aging. Because aging is a potent determinant of plasma BNP levels, BNP may be related not only to fat mass but also to muscle mass. However, no studies have evaluated the associations between body composition and plasma levels of BNP. We performed a cross-sectional study to investigate these associations in 1,431 apparently healthy middle-aged to elderly subjects. The abdominal visceral fat area and thigh muscle cross-sectional area (CSA) were quantified by computed tomography. Plasma adiponectin and leptin levels were measured as possible confounding parameters. The brachial-ankle pulse wave velocity was measured as an index of arterial stiffness, and the pulse pressure (PP) of the second peak of the radial systolic blood pressure waveform (PP2) was used as an estimate of the central PP. Plasma BNP levels were significantly and negatively associated with the visceral fat area (r = -0.13, p <0.0001) and thigh muscle CSA (r = -0.25, p <0.0001). Corrections with possible confounding parameters including age, gender, heart rate, mean blood pressure, body weight, body height, adiponectin, leptin, brachial-ankle pulse wave velocity, and PP2 eliminated the association of BNP with visceral fat area but not with thigh muscle CSA (β = -0.27, p <0.0001). These findings indicate that along with adiposity, muscle mass is an independent determinant of plasma BNP. PMID:25001150

  6. Comparison of the Utility of Preoperative versus Postoperative B-type Natriuretic Peptide for Predicting Hospital Length of Stay and Mortality after Primary Coronary Artery Bypass Grafting

    PubMed Central

    Fox, Amanda A.; Muehlschlegel, Jochen D.; Body, Simon C.; Shernan, Stanton K.; Liu, Kuang-Yu; Perry, Tjorvi E.; Aranki, Sary F.; Cook, E. Francis; Marcantonio, Edward R.; Collard, Charles D.

    2016-01-01

    Background Preoperative B-type natriuretic peptide (BNP) is known to predict adverse outcomes after cardiac surgery. The value of postoperative BNP for predicting adverse outcomes is less well delineated. The authors hypothesized that peak postoperative plasma BNP (measured postoperative days 1–5) predicts hospital length of stay (HLOS) and mortality in patients undergoing primary coronary artery bypass grafting, even after adjusting for preoperative BNP and perioperative clinical risk factors. Methods This study is a prospective longitudinal study of 1,183 patients undergoing primary coronary artery bypass grafting surgery. Mortality was defined as all-cause death within 5 yr after surgery. Cox proportional hazards analyses were conducted to separately evaluate the associations between peak postoperative BNP and HLOS and mortality. Multivariable adjustments were made for patient demographics, preoperative BNP concentration, and clinical risk factors. BNP measurements were log10 transformed before analysis. Results One hundred fifteen deaths (9.7%) occurred in the cohort (mean follow-up = 4.3 yr, range = 2.38–5.0 yr). After multivariable adjustment for preoperative BNP and clinical covariates, peak postoperative BNP predicted HLOS (hazard ratio [HR] = 1.28, 95% CI = 1.002–1.64, P = 0.049) but not mortality (HR = 1.62, CI = 0.71–3.68, P = 0.25), whereas preoperative BNP independently predicted HLOS (HR = 1.09, CI = 1.01–1.18, P = 0.03) and approached being an independent predictor of mortality (HR = 1.36, CI = 0.96–1.94, P = 0.08). When preoperative and peak postoperative BNP were separately adjusted for within the clinical multivariable models, each independently predicted HLOS (preoperative BNP HR = 1.13, CI = 1.05–1.21, P = 0.0007; peak postoperative BNP HR = 1.44, CI = 1.15–1.81, P = 0.001) and mortality (preoperative BNP HR = 1.50, CI = 1.09–2.07, P = 0.01; peak postoperative BNP HR = 2.29, CI = 1.11–4.73, P = 0.02). Conclusions Preoperative

  7. Effect of B-Type Natriuretic Peptide Level on Long-Term Outcome in Patients With End-Stage Heart Failure.

    PubMed

    Huang, Bi; Shen, Jian; Li, Lihua; Huang, Ying; Luo, Suxin

    2016-08-01

    Previous studies have demonstrated elevated B-type natriuretic peptide (BNP) level indicates a poor outcome in patients with heart failure (HF). However, some patients with end-stage HF presented with low BNP level and the impact of the nearly "normal" BNP level on long-term outcome is not well understood. Our study aimed to evaluate the association of BNP level with long-term outcome in 218 consecutive patients with dilated cardiomyopathy and end-stage HF. Sixty-two patients (28%) presented with admission BNP level ≤400 pg/ml. During a median follow-up period of 20 months (4 to 26 months), the all-cause mortality rate in patients with BNP ≤400 pg/ml was higher than in patients with BNP >400 pg/ml (76% vs 48%, p <0.001). Patients were then divided into 5 groups according to the BNP level (≤400, 401 to 1,000, 1,001 to 2,000, 2,001 to 3,000, and >3,000 pg/ml), the all-cause mortality were 76%, 41%, 40%, 49%, and 75%, respectively (p <0.001). After multivariate adjustment, both BNP ≤400 and >3,000 pg/ml were independently associated with increased risk of all-cause mortality (hazard ratios 1.87, 95% CI 1.02 to 3.42, p = 0.043 and hazard ratio 2.31, 95% CI 1.16 to 4.60, p = 0.018, respectively). In conclusion, our present study demonstrated a "U-like" shape between BNP level and all-cause mortality in end-stage HF, and the seemingly "normal" BNP level might also be a risk factor for poor outcome. Low BNP level may be a reflection of impaired neurohormonal response or altered metabolism of BNP and is associated with increased risk of poor outcome. PMID:27269584

  8. Hemoglobin and B-type natriuretic peptide preoperative values but not inflammatory markers, are associated with postoperative morbidity in cardiac surgery: a prospective cohort analytic study

    PubMed Central

    2013-01-01

    Introduction Risk stratification in cardiac surgery significantly impacts outcome. This study seeks to define whether there is an independent association between the preoperative serum level of hemoglobin (Hb), leukocyte count (LEUCO), high sensitivity C-reactive protein (hsCRP), or B-type natriuretic peptide (BNP) and postoperative morbidity and mortality in cardiac surgery. Methods Prospective, analytic cohort study, with 554 adult patients undergoing cardiac surgery in a tertiary cardiovascular hospital and followed up for 12 months. The cohort was distributed according to preoperative values of Hb, LEUCO, hsCRP, and BNP in independent quintiles for each of these variables. Results After adjustment for all covariates, a significant association was found between elevated preoperative BNP and the occurrence of low postoperative cardiac output (OR 3.46, 95% CI 1.53–7.80, p = 0.003) or postoperative atrial fibrillation (OR 3.8, 95% CI 1.45–10.38). For the combined outcome (death/acute coronary syndrome/rehospitalization within 12 months), we observed an OR of 1.93 (95% CI 1.00–3.74). An interaction was found between BNP level and the presence or absence of diabetes mellitus. The OR for non-diabetics was 1.26 (95% CI 0.61–2.60) and for diabetics was 18.82 (95% CI 16.2–20.5). Preoperative Hb was also significantly and independently associated with the occurrence of postoperative low cardiac output (OR 0.33, 95% CI 0.13–0.81, p = 0.016). Both Hb and BNP were significantly associated with the lengths of intensive care unit and hospital stays and the number of transfused red blood cells (p < 0.002). Inflammatory markers, although associated with adverse outcomes, lost statistical significance when adjusted for covariates. Conclusions High preoperative BNP or low Hb shows an association of independent risk with postoperative outcomes, and their measurement could help to stratify surgical risk. The ability to predict the onset of atrial fibrillation or

  9. An N-terminal pro-atrial natriuretic peptide (NT-proANP) 'aggregation-prone' segment involved in isolated atrial amyloidosis.

    PubMed

    Louros, Nikolaos N; Iconomidou, Vassiliki A; Tsiolaki, Paraskevi L; Chrysina, Evangelia D; Baltatzis, Georgios E; Patsouris, Efstratios S; Hamodrakas, Stavros J

    2014-01-01

    Isolated atrial amyloidosis (IAA) is a common localized form of amyloid deposition within the atria of the aging heart. The main constituents of amyloid fibrils are atrial natriuretic peptide (ANP) and the N-terminal part of its precursor form (NT-proANP). An 'aggregation-prone' heptapeptide ((114)KLRALLT(120)) was located within the NT-proANP sequence. This peptide self-assembles into amyloid-like fibrils in vitro, as electron microscopy, X-ray fiber diffraction, ATR FT-IR spectroscopy and Congo red staining studies reveal. Consequently, remedies/drugs designed to inhibit the aggregation tendency of this 'aggregation-prone' segment of NT-proANP may assist in prevention/treatment of IAA, congestive heart failure (CHF) or atrial fibrillation (AF). PMID:24220659

  10. [Clinical significance of natriuretic peptides in the differential diagnosis of dyspnea].

    PubMed

    Špác, Jiří

    2016-01-01

    Acute dyspnea is one of the most common emergency department symptoms. But early diagnosis and treatment could be e challenging because of multiple potential causes. The gold standard biomarkers in cardiac dyspnea are B-type natriuretic peptide (BNP) and N-terminal pro-B-type (natriuretic peptide NT-pro BNP), which play an important role in the diagnosis, prognosis, and management of acute decompensated heart failure. The purpose of this review is to analyze diagnostic potential of BNP and NT-pro BNP biomarkers use in patients with acute dyspnea. BNP and NT-proBNP are markers of cardiac stress but are not cardiac-specific. They have comparable clinical utility, and both help in excluding acute cardiac dyspnea but they cannot reliably discriminate systolic from diastolic HF.Key word: acute dyspnea - natriuretic peptide - heart failure. PMID:27627091

  11. NT-pro brain natriuretic peptide levels and the risk of death in the cooperative study of sickle cell disease.

    PubMed

    Machado, Roberto F; Hildesheim, Mariana; Mendelsohn, Laurel; Remaley, Alan T; Kato, Gregory J; Gladwin, Mark T

    2011-08-01

    Epidemiological studies support a hypothesis that pulmonary hypertension (PH) is a common complication of sickle cell disease (SCD) that is associated with a high risk of death and evolves as a complication of haemolytic anaemia. This fundamental hypothesis has been recently challenged and remains controversial. In order to further test this hypothesis in a large and independent cohort of SCD patients we obtained plasma samples from the Cooperative Study of Sickle Cell Disease (CSSCD) for analysis of a biomarker, N-terminal-pro brain natriuretic peptide (NT-proBNP), which is elevated in the setting of pulmonary arterial and venous hypertension. A NT-pro-BNP value previously identified to predict PH in adults with SCD was used to determine the association between the risk of mortality in 758 CSSCD participants (428 children and 330 adults). An abnormally high NT-proBNP level ≥160ng/l was present in 27·6% of adult SCD patients. High levels were associated with markers of haemolytic anaemia, such as low haemoglobin level (P<0·001), high lactate dehydrogenase (P<0·001), and high total bilirubin levels (P<0·007). A NT-proBNP level ≥160ng/l was an independent predictor of mortality (RR 6·24, 95% CI 2·9-13·3, P<0·0001). These findings provide further support for an association between haemolytic anaemia and cardiovascular complications in this patient population. PMID:21689089

  12. The Effect of Anesthesia Method on Serum Level of Pro-Brain Natriuretic Peptide in Patients Undergoing Orthopedic Surgery

    PubMed Central

    Mirkheshti, Alireza; Heidari Farzan, Masoume; Nasiri, Yashar; Mottaghi, Kamran; Dabbagh, Ali

    2015-01-01

    Background: Surgical stress response is among the most severe stress tolerated by the patient, which needs suppression by anesthesia. Objectives: We assessed the effect of three methods of anesthesia on postoperative levels of pro-brain natriuretic peptide (pro-BNP) to determine the most effective one in preventing surgical stress response. Patients and Methods: In a randomized clinical trial, 120 patients who were 18 to 65 years old and met inclusion and exclusion criteria were selected and randomly allocated to three groups of 40:Group A, general anesthesia plus epidural catheter; Group B, general anesthesia and intravenous patient-controlled analgesia; and Group C, spinal anesthesia plus intravenous patient-controlled analgesia. Results: There was no difference between three groups for basic characteristics and variables and baseline pro-BNP levels; however, postoperative pro-BNP levels in Groups A, B, and C were respectively63.8 ± 10.1, 83.2 ± 12.3, and 51.5 ± 8.5 ng/L (ANOVA, P = 0.01). Conclusions: The results of the current study suggested that spinal anesthesia plus intravenous patient-controlled analgesia have the most favorable cardiac effects regarding postoperative levels of pro-BNP. PMID:25893184

  13. The Association of Menopausal Age and NT-proBrain Natriuretic Peptide: The Multi-Ethnic Study of Atherosclerosis

    PubMed Central

    Ebong, Imo A.; Watson, Karol E.; Goff, David C.; Bluemke, David A.; Srikanthan, Preethi; Horwich, Tamara; Bertoni, Alain G.

    2014-01-01

    Objective Menopausal age could affect the risk of developing cardiovascular disease (CVD). The purpose of this study was to investigate the associations of early menopause (menopause occurring before 45 years of age) and menopausal age with NT-pro brain natriuretic peptide (NT-proBNP), a potential risk marker of CVD and heart failure (HF). Methods Our cross-sectional study included 2275 postmenopausal women, aged 45–85 years, without clinical CVD (2000–2002), from the Multi-Ethnic Study of Atherosclerosis. Participants were classified as having or not having early menopause. NT-proBNP was log-transformed. Multivariable linear regression was used for analysis. Results There were 561 women with early menopause. The median NT-proBNP value was 79.0 (41.1–151.6) pg/ml for all participants with values of 83.4 (41.4–164.9) pg/ml and 78.0 (40.8–148.3) pg/ml for women with and without early menopause respectively. The mean (SD) age was 65 (10.1) and 65 (8.9) years for women with and without early menopause respectively. There were no significant interactions between menopausal age and ethnicity. In multivariable analysis, early menopause was associated with a 10.7% increase in NT-proBNP while each year increase in menopausal age was associated with a 0.7% decrease in NT-proBNP. Conclusion Early menopause is associated with greater NT-proBNP levels while each year increase in menopausal age is associated with lower NT-proBNP levels in postmenopausal women. PMID:25290536

  14. N-terminal-pro-brain natriuretic peptide, a surrogate biomarker of combined clinical and hemodynamic outcomes following percutaneous transvenous mitral commissurotomy

    PubMed Central

    Ranganayakulu, K.P.; Rajasekhar, D.; Vanajakshamma, V.; Santosh Kumar, C.; Vasudeva Chetty, P.

    2015-01-01

    Aim To examine the relationship between plasma levels of N-terminal-proB type natriuretic peptide (NT-proBNP) and various echocardiographic and hemodynamic parameters in patients with mitral stenosis undergoing percutaneous transvenous mitral commissurotomy (PTMC). Materials and methods The study population consisted of 100 patients with rheumatic mitral stenosis who underwent PTMC. NT-proBNP levels in these patients were measured before PTMC and 48 hours after PTMC. These levels were then correlated with various echocardiographic and hemodynamic parameters measured before and after PTMC. Results Eighty-one percent of the study population were women, and the most common presenting symptom was dyspnea which was present in 94% of the patients. Dyspnea New York Heart Association class correlated significantly with baseline NT-proBNP levels (r = 0.63; p < 0.01). The plasma NT-proBNP levels in these patients increased as echocardiogram signs of left atrial enlargement and right ventricular hypertrophy developed (r = 0.59, p < 0.01). Patients in atrial fibrillation had significantly higher NT-proBNP levels than patients in sinus rhythm. Baseline NT-proBNP levels correlated significantly with left atrial volume (r = 0.38; p < 0.01), left atrial volume index (r = 0.45; p < 0.01), systolic pulmonary artery pressures (r = 0.42; p < 0.01), and mean pulmonary artery pressures (r = 0.41; p < 0.01). All patients who underwent successful PTMC showed a significant decrease in NT-proBNP (decreased from a mean 763.8 pg/mL to 348.6 pg/mL) along with a significant improvement in all echocardiographic and hemodynamic parameters (p < 0.01). The percent change in NT-proBNP correlated significantly with the percent improvement noted with left atrial volume (r = 0.39; p < 0.01), left atrial volume index (r = 0.41; p < 0.01), systolic (r = 0.32, p < 0.01), and mean pulmonary artery pressures (r = 0.31, p < 0.01). Conclusions The decrease in NT-pro

  15. Amino-Terminal Fragment of the Prohormone Brain-type Natriuretic Peptide (NT-proBNP) in Rheumatoid Arthritis

    PubMed Central

    Solus, Joseph; Chung, Cecilia P.; Oeser, Annette; Avalos, Ingrid; Gebretsadik, Tebeb; Shintani, Ayumi; Raggi, Paolo; Sokka, Tuulikki; Pincus, Theodore; Stein, C. Michael

    2008-01-01

    Objective Increased concentrations of amino-terminal prohormone brain-type natriuretic peptide (NT-proBNP) are associated with cardiovascular morbidity and mortality, but little is known about their relationship to chronic inflammation. Patients with rheumatoid arthritis (RA) have chronic inflammation, increased arterial stiffness and accelerated coronary atherosclerosis. We tested the hypothesis that NT-proBNP concentrations are elevated in patients with RA, and are associated with coronary artery calcification and markers of inflammation. Methods In 159 subjects with RA (90 patients with early RA and 69 patients with longstanding RA) without heart failure and 88 control subjects, we measured serum concentrations of NT-proBNP, interleukin (IL)-6, and tumor necrosis factor-α (TNF-α), and coronary calcification. Results NT-proBNP concentrations were elevated in patients with long-standing RA [median (IQR): 142.8 (54.8–270.5) pg/mL] and those with early RA [58.1 (19.4–157.6) pg/mL] compared to controls [18.1 (3.2–46.0) pg/mL, P<0.001]. In patients with RA, NT-proBNP concentrations were associated with age (ρ=0.35, P<0.001), IL-6 (ρ=0.33, P<0.001), TNF-α (ρ=0.23, P=0.003), CRP (ρ=0.21, P=0.01), coronary calcium score (ρ=0.30, P<0.001), systolic blood pressure (ρ=0.30, p<0.001), and disease activity (ρ=0.29, P<0.001). After adjustment for age, race and sex the associations between NT-proBNP concentrations and disease activity (P<0.001), TNF-α (P<0.001), IL-6 (P=0.04) and CRP concentrations (P=0.02) remained significant, but those with systolic blood pressure (P=0.10) and coronary calcium score (P=0.27) were attenuated. Conclusions NT-proBNP concentrations are increased in patients with RA without clinical heart failure and may indicate subclinical cardiovascular disease and a chronic inflammatory state. PMID:18759301

  16. Natriuretic peptides in fish physiology.

    PubMed

    Loretz, C A; Pollina, C

    2000-02-01

    Natriuretic peptides exist in the fishes as a family of structurally-related isohormones including atrial natriuretic peptide (ANP), C-type natriuretic peptide (CNP) and ventricular natriuretic peptide (VNP); to date, brain natriuretic peptide (or B-type natriuretic peptide, BNP) has not been definitively identified in the fishes. Based on nucleotide and amino acid sequence similarity, the natriuretic peptide family of isohormones may have evolved from a neuromodulatory, CNP-like brain peptide. The primary sites of synthesis for the circulating hormones are the heart and brain; additional extracardiac and extracranial sites, including the intestine, synthesize and release natriuretic peptides locally for paracrine regulation of various physiological functions. Membrane-bound, guanylyl cyclase-coupled natriuretic peptide receptors (A- and B-types) are generally implicated in mediating natriuretic peptide effects via the production of cyclic GMP as the intracellular messenger. C- and D-type natriuretic peptide receptors lacking the guanylyl cyclase domain may influence target cell function through G(i) protein-coupled inhibition of membrane adenylyl cyclase activity, and they likely also act as clearance receptors for circulating hormone. In the few systems examined using homologous or piscine reagents, differential receptor binding and tissue responsiveness to specific natriuretic peptide isohormones is demonstrated. Similar to their acute physiological effects in mammals, natriuretic peptides are vasorelaxant in all fishes examined. In contrast to mammals, where natriuretic peptides act through natriuresis and diuresis to bring about long-term reductions in blood volume and blood pressure, in fishes the primary action appears to be the extrusion of excess salt at the gills and rectal gland, and the limiting of drinking-coupled salt uptake by the alimentary system. In teleosts, both hypernatremia and hypervolemia are effective stimuli for cardiac secretion of

  17. N-Terminal Pro-Brain Natriuretic Peptide Is Associated with a Future Diagnosis of Cancer in Patients with Coronary Artery Disease

    PubMed Central

    Tarín, Nieves; Cristóbal, Carmen; Lorenzo, Óscar; Blanco-Colio, Luis; Martín-Ventura, José Luis; Huelmos, Ana; Alonso, Joaquín; Aceña, Álvaro; Pello, Ana; Carda, Rocío; Asensio, Dolores; Mahíllo-Fernández, Ignacio; López Bescós, Lorenzo; Egido, Jesús; Farré, Jerónimo

    2015-01-01

    Objective Several papers have reported elevated plasma levels of natriuretic peptides in patients with a previous diagnosis of cancer. We have explored whether N-terminal pro-brain natriuretic peptide (NT-proBNP) plasma levels predict a future diagnosis of cancer in patients with coronary artery disease (CAD). Methods We studied 699 patients with CAD free of cancer. At baseline, NT-proBNP, galectin-3, monocyte chemoattractant protein-1, soluble tumor necrosis factor-like weak inducer of apoptosis, high-sensitivity C-reactive protein, and high-sensitivity cardiac troponin I plasma levels were assessed. The primary outcome was new cancer diagnosis. The secondary outcome was cancer diagnosis, heart failure requiring hospitalization, or death. Results After 2.15±0.98 years of follow-up, 24 patients developed cancer. They were older (68.5 [61.5, 75.8] vs 60.0 [52.0, 72.0] years; p=0.011), had higher NT-proBNP (302.0 [134.8, 919.8] vs 165.5 [87.4, 407.5] pg/ml; p=0.040) and high-sensitivity C-reactive protein (3.27 [1.33, 5.94] vs 1.92 [0.83, 4.00] mg/L; p=0.030), and lower triglyceride (92.5 [70.5, 132.8] vs 112.0 [82.0, 157.0] mg/dl; p=0.044) plasma levels than those without cancer. NT-proBNP (Hazard Ratio [HR]=1.030; 95% Confidence Interval [CI]=1.008-1.053; p=0.007) and triglyceride levels (HR=0.987; 95%CI=0.975-0.998; p=0.024) were independent predictors of a new cancer diagnosis (multivariate Cox regression analysis). When patients in whom the suspicion of cancer appeared in the first one-hundred days after blood extraction were excluded, NT-proBNP was the only predictor of cancer (HR=1.061; 95%CI=1.034-1.088; p<0.001). NT-proBNP was an independent predictor of cancer, heart failure, or death (HR=1.038; 95%CI=1.023-1.052; p<0.001) along with age, and use of insulin and acenocumarol. Conclusions NT-proBNP is an independent predictor of malignancies in patients with CAD. New studies in large populations are needed to confirm these findings. PMID:26046344

  18. Cost-effectiveness of using N-terminal pro-brain natriuretic peptide to guide the diagnostic assessment and management of dyspneic patients in the emergency department.

    PubMed

    Siebert, Uwe; Januzzi, James L; Beinfeld, Molly T; Cameron, Renee; Gazelle, G Scott

    2006-09-15

    The cost-effectiveness of N-terminal pro-brain natriuretic peptide (NT-pro-BNP) in dyspneic patients in emergency departments (EDs) is unknown. The objective of this study was to assess the cost-effectiveness of NT-pro-BNP testing for the evaluation and initial management of patients with dyspnea in the ED setting. A decision model was developed to evaluate the cost-effectiveness of diagnostic assessment and patient management guided by NT-pro-BNP, compared with standard clinical assessment. The model includes the diagnostic accuracy of the 2 strategies for congestive heart failure and resulting events at 60-day follow-up. Clinical data were obtained from a prospective blinded study of 599 patients presenting to the ED with dyspnea. Costs were based on the Massachusetts General Hospital cost accounting database. The model predicted serious adverse events during follow-up (i.e., urgent care visits, repeat ED presentations, rehospitalizations) and direct medical costs for echocardiograms and hospitalizations. NT-pro-BNP-guided assessment was associated with a 1.6% relative reduction of serious adverse event risk and a 9.4% reduction in costs, translating into savings of $474 per patient, compared with standard clinical assessment. In a sensitivity analysis considering mortality, NT-pro-BNP testing was associated with a 1.0% relative reduction in post-discharge mortality. The optimal use of NT-pro-BNP guidance could reduce the use of echocardiography by up to 58%, prevent 13% of initial hospitalizations, and reduce hospital days by 12%. In conclusion, on the basis of this model, the use of NT-pro-BNP in the diagnostic assessment and subsequent management of patients with dyspnea in the ED setting could lead to improved patient care while providing substantial cost savings to the health care system. PMID:16950189

  19. N-Terminal Pro-Brain Natriuretic Peptide Is a Useful Prognostic Marker in Patients with Pre-Capillary Pulmonary Hypertension and Renal Insufficiency

    PubMed Central

    Lüneburg, Nicole; Griesch, Elisabeth; Bokemeyer, Carsten; Grünig, Ekkehard; Klose, Hans

    2014-01-01

    N-terminal pro-brain natriuretic peptide (NT-proBNP) is a routinely used prognostic parameter in patients with pre-capillary pulmonary hypertension (PH). As it accumulates in the presence of impaired renal function, the clinical utility of NT-proBNP in PH patients with concomitant renal insufficiency remains unclear. In a retrospective approach, patients with pre-capillary PH (group I or IV) and concomitant renal insufficiency at time of right heart catheterization (glomerular filtration rate (GFR) ≤60 ml/min/1.73 m2) were identified out of all prevalent pre-capillary PH patients treated at a single center. Forty patients with renal insufficiency (25.8%) were identified and matched regarding hemodynamic parameters with a control group of 56 PH patients with normal renal function (GFR >60 ml/min/1.73 m2). Correlations of NT-proBNP levels with hemodynamic and prognostic parameters (time to clinical worsening and overall survival) were assessed. Overall, GFR correlated inversely with NT-proBNP and had the strongest influence on NT-proBNP levels in a stepwise multiple linear regression model including hemodynamic parameters and age (r2 = 0.167). PH patients with renal insufficiency had significant higher levels of NT-proBNP (median: 1935 ng/l vs. 573 ng/l, p = 0.001). Nevertheless, NT-proBNP correlated with invasive hemodynamic parameters in these patients. Using higher cut-off values than in patients with preserved renal function, NT-proBNP levels were significantly associated with time to clinical worsening (>1660 ng/l, p = 0.001) and survival (>2212 ng/l, p = 0.047) in patients with renal insufficiency. Multivariate Cox’s proportional hazards analysis including established prognostic parameters, age and GFR confirmed NT-proBNP as an independent risk factor for clinical worsening in PH patients with renal insufficiency (hazard ratio 4.8, p = 0.007). Thus, in a retrospective analysis we showed that NT-proBNP levels correlated with hemodynamic

  20. The diagnostic performance of mid-regional portion of pro-atrial natriuretic peptide for the detection of left ventricular hypertrophy in Caucasian hypertensive patients.

    PubMed

    Bhandari, S S; Davies, J E; Struck, J; Ng, L L

    2012-12-01

    Left ventricular hypertrophy (LVH) is predictive of cardiovascular disease. The vasodilator, natriuretic and diuretic actions of atrial natriuretic peptide (ANP) support a role in the pathophysiology of hypertension. Measuring the redundant precursor fragment mid-regional portion of pro-atrial natriuretic peptide (MRproANP) overcomes the technical difficulties of quantifying the bioactive ANP. This study sought to investigate the diagnostic and prognostic utility of MRproANP in a hypertensive Caucasian patient population. A total of 194 hypertensive patients (39 patients with LVH, 69±7.82 years of age, 74% female vs 155 patients without LVH, 68±6.51 years of age, 71% female) were derived from a screening study. Plasma MRproANP concentrations were quantified using immunoluminometric assays. Hypertensive patients with LVH had higher MRproANP concentrations than those without LVH (103.04 (50.58) vs 84.11 pmol l(-1) (44.82); P=0.014). Independent predictors of left ventricular mass index were LogMRproANP (P=0.022), male gender (P<0.001), body mass index (P=0.001) and history of angina or myocardial infarction (P=0.009). The receiver operating curve for MRproANP for the detection of LVH was limited, yielding an area under the curve of only 0.628 (confidence interval 0.523-0.733; P=0.014). Therefore, the role of MRproANP may not lie in the diagnosis of LVH but in monitoring the response to therapy. A nonsignificant trend towards greater mortality in patients with above-median MRproANP levels compared with below-median levels (P=0.167) was observed. Larger studies are required to assess its prognostic utility further. PMID:22113442

  1. Concentrations of N-terminal pro-brain natriuretic peptide and troponin T in plasma of 75-year-old apparently healthy persons.

    PubMed

    Huber, Klaus Roland; Mostafaie, Nazanin; Bauer, Kurt; Worofka, Brigitte; Kittl, Eva; Hofmann, Jörg; Hejtman, Milos; Redei, Karoly; Jungwirth, Susanne; Fischer, Peter; Tragl, Karl-Heinz

    2004-01-01

    Clinical chemical reference values for older persons are sparse and mostly intermixed with those for younger persons. We had a unique opportunity to obtain blood samples from volunteers who were 75 years old and living in two districts of Vienna, Austria. Consequently, we utilized stored plasma samples to obtain reference intervals for 120 apparently healthy 75-year-old participants for pro-brain natriuretic peptide (proBNP), as well as for troponin T. The N-terminal (NT)-proBNP protein assay is currently used as a diagnostic and prognostic aid in patients with heart failure and as a prognostic marker in acute coronary syndromes. Specifically, the concentration of NT-proBNP in serum or plasma aids in the prognosis of ventricular systolic dysfunction and helps to differentiate between cardiac and non-cardiac causes. The median NT-proBNP plasma value for men and women in our cohort was calculated as 98 pg/ml, comparing favorably with reported values, in that a NT-proBNP concentration less than 100 pg/ml excludes acutely decompensated heart failure. Our calculated 97.5 percentile was slightly higher (359 pg/ml) than the 97.5 percentile in a group of 50-65-year-old persons (198 and 222 pg/ml for men and women, respectively) revealing the influence of age on this parameter. Because of its high tissue-specificity, cardiac troponin T is a cardiospecific, highly sensitive marker for myocardial damage. However, the troponin T concentrations in the plasma specimens from this cohort were all below the detection limit of 0.01 ng/ml, preventing any further data handling. PMID:15576307

  2. The Association between N-terminal Pro-Brain Natriuretic Peptide Levels in the Umbilical Vein and Amniotic Fluid Volume Abnormalities.

    PubMed

    Ersoy, Ali Ozgur; Ozler, Sibel; Oztas, Efser; Ersoy, Ebru; Ergin, Merve; Erkaya, Salim; Uygur, Dilek

    2016-04-01

    Purpose The amniotic fluid volume (AFV) is known as a predictor for the wellness of a fetus. We aimed to investigate whether N-terminal pro-brain natriuretic peptide (NTproBNP) levels reflect AFV abnormalities in otherwise normal fetuses. Methods We recruited 24 women with isolated oligohydramnios, 23 women with isolated polyhydramnios, and 36 women with normal AFV at a tertiary referral center. NT-proBNP levels in umbilical venous samples and the individual characteristics of the three groups were compared. One-way ANOVA and Kruskal-Wallis analysis of variance were used for multi-group comparisons of continuous variables. When a significant difference was detected, the Scheffe test was performed as a post-hoc analysis. Proportions were compared using the Chi-square (χ2) test. Results Maternal age, body mass indices, weight gained in pregnancy and NT-proBNP levels were similar among the three groups. Apgar scores at 1 and 5 minutes significantly correlated with NT-proBNP levels in all newborns (Spearman's r = 0.23; p = 0.03 and Spearman's r = 0.24; p = 0.02, respectively). The umbilical venous NT-proBNP levels did not differ between newborns who needed mechanical ventilation and those who didn't (p = 0.595). Conclusions NT-proBNP is a biomolecule that may provide insights into the pathogenesis of fetal circulatory problems and subsequent renal failure. Further investigations are warranted. PMID:27096950

  3. N-terminal pro-brain natriuretic peptide in a novel screening algorithm for pulmonary arterial hypertension in systemic sclerosis: a case-control study

    PubMed Central

    2012-01-01

    Introduction Pulmonary arterial hypertension is a major cause of mortality in systemic sclerosis. N-terminal pro-brain natriuretic peptide (NT-proBNP) has emerged as a candidate biomarker that may enable the early detection of systemic sclerosis-related pulmonary arterial hypertension (SSc-PAH). The objective of our study was to incorporate NT-proBNP into a screening algorithm for SSc-PAH that could potentially replace transthoracic echocardiography (TTE) as a more convenient and less costly "first tier" test. Methods NT-proBNP levels were measured in patients from four clinical groups: a group with right heart catheter (RHC)-diagnosed SSc-PAH before commencement of therapy for PAH; a group at high risk of SSc-PAH based on TTE; a group with interstitial lung disease; and systemic sclerosis (SSc) controls with no cardiopulmonary complications. NT-proBNP levels were compared by using ANOVA and correlated with other clinical variables by using simple and multiple linear regression. ROC curve analyses were performed to determine the optimal cut point for NT-proBNP and other clinical variables in prediction of PAH. Results NT-proBNP was highest in the PAH group compared with other groups (P < 0.0001), and higher in the risk group compared with controls (P < 0.0001). NT-proBNP was positively correlated with systolic pulmonary artery pressure (PAP) on TTE (P < 0.0001), and mean PAP (P = 0.013), pulmonary vascular resistance (P = 0.005), and mean right atrial pressure (P = 0.006) on RHC. A composite model wherein patients screened positive if NT-proBNP was ≥ 209.8 pg/ml, and/or DLCOcorr was < 70.3% with FVC/DLCOcorr ≥ 1.82, had a sensitivity of 100% and specificity of 77.8% for SSc-PAH. Conclusion We have proposed a screening algorithm for SSc-PAH, incorporating NT-proBNP level and PFTs. This model has high sensitivity and specificity for SSc-PAH and, if positive, should lead to TTE and confirmatory testing for PAH. This screening algorithm must be validated

  4. Relationship between N-Terminal Pro-Brain Natriuretic Peptide, Obesity and the Risk of Heart Failure in Middle-Aged German Adults

    PubMed Central

    Wirth, Janine; Buijsse, Brian; di Giuseppe, Romina; Fritsche, Andreas; Hense, Hans W.; Westphal, Sabine; Isermann, Berend; Boeing, Heiner; Weikert, Cornelia

    2014-01-01

    Background Both high concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) and obesity are related to higher heart failure risk. However, inverse relationships between NT-proBNP and obesity have been reported. Therefore, it was investigated whether the association between NT-proBNP and the risk of heart failure differed according to obesity status. Methods A case-cohort study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam, comprising a random sub-cohort (non-cases = 1,150, cases = 13, mean age: 50.5±9.0 years) and heart failure cases outside the sub-cohort (n = 197). Weighted Cox proportional hazards regression was used to examine the association between NT-proBNP and heart failure risk during a mean follow-up time of 8 years. Stratified analyses were performed according to obesity status as defined by body mass index (<30 kg/m2 versus ≥30 kg/m2). Results Overall, NT-proBNP was associated with higher risk of heart failure after multivariable adjustment (hazard ratio (HR) and 95% confidence interval (CI): 2.56 (1.49–4.41) for the top versus bottom tertile of NT-proBNP, ptrend:<0.01). In stratified analyses, the shape of association was linear in non-obese and U-shaped in obese participants: HRs (95%CI) from the first to the third tertile of NT-proBNP for non-obese: reference, 1.72 (0.85–3.49), 2.72 (1.42–5.22), and for obese: 3.29 (1.04–10.40), reference, 3.74 (1.52–9.21). Conclusions Although high circulating concentrations of NT-proBNP were positively associated with incident heart failure in the entire sample, the association differed according to obesity status. In obese, an increased risk of heart failure was also observed in those with low NT-proBNP concentrations. If confirmed, this observation warrants further investigation to understand underlying pathophysiological mechanisms. PMID:25423197

  5. Growth-differentiation factor-15, endoglin and N-terminal pro-brain natriuretic peptide induction in athletes participating in an ultramarathon foot race.

    PubMed

    Tchou, Isabelle; Margeli, Alexandra; Tsironi, Maria; Skenderi, Katerina; Barnet, Marc; Kanaka-Gantenbein, Christina; Papassotiriou, Ioannis; Beris, Photis

    2009-09-01

    We investigated the actions of growth-differentiation factor (GDF)-15, endoglin and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) in 15 male athletes who participated in the ultradistance foot race of the 246 km 'Sparthathlon'. Measurements were performed before (phase I), at the end of the race (phase II) and 48 h post-race (phase III). GDF-15 and endoglin serum concentrations were determined with enzyme-linked immunosorbent assay and NT-pro-BNP plasma levels by electrochemiluminescence. GDF-15 levels were increased from phase I (563.9 +/- 57.1 pg ml(-1)) to phase II (2311.1 +/- 462.3 pg ml(-1)) and decreased at phase III (862.0 +/- 158.0 pg ml(-1)) (p < 0.0002). NT-pro-BNP levels followed a similar pattern to that of GDF-15 from 38.1 +/- 4.8 pg ml(-1) at phase I to 1280.6 +/- 259.0 pg ml(-1) at phase II and 89.8 +/- 13.6 pg ml(-1) at phase III (p < 0.0001) and at the same time points, endoglin levels were 4.7 +/- 0.2 ng ml(-1) at phase I, 5.8 +/- 0.2 ng ml(-1) at phase II and 4.3 +/- 0.2 ng ml(-1) at phase III (p < 0.002). These findings indicate that circulating GDF-15, endoglin and NT-pro-BNP levels reflect a transient endothelial dysfunction in these athletes who participated in a foot race consisting of continuous, prolonged and brisk exercise. PMID:19563304

  6. Relationship Between Prohormone Brain Natriuretic Peptide (NT-proBNP) Level and Severity of Pulmonary Dysfunction in Patients With Chronic Congestive Heart Failure

    PubMed Central

    Nazemiyeh, Masoud; Sharifi, Akbar; Amiran, Farhad; Pourafkari, Leili; Taban Sadeghi, Mohammadreza; Namdar, Hossein; Abbasnezhad, Mohsen

    2015-01-01

    Introduction: Congestive heart failure (CHF) is a common disease and its prevalence is increasing in industrialized countries. NT-proBNP measurement is an established diagnostic test for diagnosis of CHF in patients who present to emergency room with acute dyspnea. The primary object of this study was to determine the relationship between levels of brain natriuretic peptide precursor and severity of lung function impairment in patients with chronic CHF. Methods: This cross-sectional and analytical study that performed in Tuberculosis and Lung Disease Research Center of Tabriz University of Medical Sciences on 95 patients with chronic heart failure, and relation between NT-proBNP levels and pulmonary function parameters were examined. Results: Sixty-four patients were male and 31 were female. The average age of male and females was 62.90 ± 11.54 and 61.61 ± 11.98 years, respectively. A significant inverse linear correlation was found between NT-proBNP and FEV1 (P < 0.001, r = -0.367), FVC (P < 0.001, r = -0.444), TLC (P = 0.022, r = -0.238), maximal midexpiratory flow (MMEF) (P = 0.047, r = -0.207) and left ventricular ejection fraction (LVEF) (P < 0.001, r = -0.461). A significant positive linear correlation was found between NT-proBNP and FEV1/FVC (P = 0.013, r = 0.257), RV/TLC (P = 0.003, r=0.303) and 5 Hz Raw (r = 0.231, P = 0.024). Conclusion: This study showed that, both restrictive and obstructive ventilator impairments can occur in chronic CHF and as NT-proBNP increases appropriate to hemodynamic deterioration, pulmonary dysfunction increases. PMID:25859312

  7. Multiple biomarker strategy based on parathyroid hormone and natriuretic peptides testing for improved prognosis of chronic heart failure.

    PubMed

    Gruson, Damien; Ahn, Sylvie A; Rousseau, Michel F

    2015-02-01

    Biomarkers offer new perspectives for a more personalized management of patients with heart failure (HF). Hyperparathyroidism is common in HF patients and parathyroid hormone (PTH) testing might provide added value for the prognostication of HF patients. Our objectives were therefore to determine the efficiency of multiple biomarker strategy based on PTH and natriuretic peptides measurement for the risk stratification of patients with HF. Circulating concentrations of bioactive PTH 1-84 and natriuretic peptides, B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP), were measured with automated immunoassays in 45 healthy individuals and 137 HF patients with reduced left ventricular ejection fraction. Circulating levels of PTH 1-84 and natriuretic peptides were significantly increased in HF patients in comparison to HF patients. Over a long-term follow-up, baseline PTH 1-84 levels were related to the risk of cardiovascular death. Furthermore, in multiple biomarker approach, PTH measurement was additive to BNP and NT-proBNP testing for the cardiovascular risk assessment of HF patients. In conclusion, the combination of PTH 1-84 and natriuretic peptides testing improves the prognostication of HF patients and might allowed more personalized approach for risk stratification and treatment selection in HF patients. PMID:25572303

  8. The inclusion of N-terminal pro-brain natriuretic peptide in a sensitive screening strategy for systemic sclerosis-related pulmonary arterial hypertension: a cohort study

    PubMed Central

    2013-01-01

    Introduction Pulmonary arterial hypertension (PAH) is a major cause of mortality in systemic sclerosis (SSc). Screening guidelines for PAH recommend multiple investigations, including annual echocardiography, which together have low specificity and may not be cost-effective. We sought to evaluate the predictive accuracy of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) in combination with pulmonary function tests (PFT) (‘proposed’ algorithm) in a screening algorithm for SSc-PAH. Methods We evaluated our proposed algorithm (PFT with NT-proBNP) on 49 consecutive SSc patients with suspected pulmonary hypertension undergoing right heart catherisation (RHC). The predictive accuracy of the proposed algorithm was compared with existing screening recommendations, and is presented as sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Results Overall, 27 patients were found to have pulmonary hypertension (PH) at RHC, while 22 had no PH. The sensitivity, specificity, PPV and NPV of the proposed algorithm for PAH was 94.1%, 54.5%, 61.5% and 92.3%, respectively; current European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines achieved a sensitivity, specificity, PPV and NPV of 94.1%, 31.8%, 51.6% and 87.5%, respectively. In an alternate case scenario analysis, estimating a PAH prevalence of 10%, the proposed algorithm achieved a sensitivity, specificity, PPV and NPV for PAH of 94.1%, 54.5%, 18.7% and 98.8%, respectively. Conclusions The combination of NT-proBNP with PFT is a sensitive, yet simple and non-invasive, screening strategy for SSc-PAH. Patients with a positive screening result can be referred for echocardiography, and further confirmatory testing for PAH. In this way, it may be possible to shift the burden of routine screening away from echocardiography. The findings of this study should be confirmed in larger studies. PMID:24246100

  9. Mid-regional pro-atrial natriuretic peptide as a prognostic marker for all-cause mortality in patients with symptomatic coronary artery disease.

    PubMed

    von Haehling, Stephan; Papassotiriou, Jana; Hartmann, Oliver; Doehner, Wolfram; Stellos, Konstantinos; Geisler, Tobias; Wurster, Thomas; Schuster, Andreas; Botnar, Rene M; Gawaz, Meinrad; Bigalke, Boris

    2012-11-01

    In the present study, we investigated the prognostic value of MR-proANP (mid-regional pro-atrial natriuretic peptide). We consecutively evaluated a catheterization laboratory cohort of 2700 patients with symptomatic CAD (coronary artery disease) [74.1% male; ACS (acute coronary syndrome), n=1316; SAP (stable angina pectoris), n=1384] presenting to the Cardiology Department of a large primary care hospital, all of whom underwent coronary angiography. Serum MR-proANP and other laboratory markers were sampled at the time of presentation or in the catheterization laboratory. Clinical outcome was assessed by hospital chart analysis and telephone interviews. The primary end point was all-cause death at 3 months after enrolment. Follow-up data were complete in 2621 patients (97.1%). Using ROC (receiver operating characteristic) curves, the AUC (area under the curve) of 0.73 [95% CI (confidence interval), 0.67-0.79] for MR-proANP was significantly higher compared with 0.58 (95% CI, 0.55-0.62) for Tn-I (troponin-I; DeLong test, P=0.0024). According to ROC analysis, the optimal cut-off value of MR-proANP was at 236 pmol/l for all-cause death, which helped to find a significantly increased rate of all-cause death (n=76) at 3 months in patients with elevated baseline concentrations (≥236 pmol/l) compared with patients with a lower concentration level in Kaplan-Meier survival analysis (log rank, P<0.001). The predictive performance of MR-proANP was independent of other clinical variables or cardiovascular risk factors, and superior to that of Tn-I or other cardiac biomarkers (all: P<0.0001). MR-proANP may help in the prediction of all-cause death in patients with symptomatic CAD. Further studies should verify its prognostic value and confirm the appropriate cut-off value. PMID:22690794

  10. Increased Epicardial Fat Thickness Correlates with Aortic Stiffness and N-Terminal Pro-Brain Natriuretic Peptide Levels in Acute Ischemic Stroke Patients

    PubMed Central

    Unal, Yasemin; Basaran, Ozcan; Akin, Fatih; Emir, Gulser Karadaban; Kutlu, Gulnihal; Biteker, Murat

    2016-01-01

    Epicardial fat, a metabolically active tissue, has emerged as a risk factor and active player in metabolic and cardiovascular diseases. We investigated epicardial fat thickness in patients who had sustained an acute ischemic stroke, and we evaluated the relationship of epicardial fat thickness with other prognostic factors. We enrolled 61 consecutive patients (age, ≥18 yr) who had sustained a first acute ischemic stroke and had been admitted to our hospital within 24 hours of the onset of stroke symptoms. The control group comprised 82 consecutive sex- and age-matched patients free of past or current stroke who had been admitted to our cardiology clinics. Blood samples were taken for measurement of N-terminal pro-brain natriuretic peptide (NT-proBNP) levels at admission. Aortic stiffness indices and epicardial fat thickness were measured by means of transthoracic echocardiography within the first 48 hours. In comparison with the control group, the patients with acute ischemic stroke had significantly higher epicardial fat thickness (4.8 ± 0.9 vs 3.8 ± 0.7 mm; P <0.001), lower aortic distensibility (2.5 ± 0.8 vs 3.4 ± 0.9 cm2·dyn−1; P <0.001) and lower aortic strain (5.5% ± 1.9% vs 6.4% ± 1.8%; P=0.003). We found a significant association between epicardial fat thickness, NT-proBNP levels, and arterial dysfunction in patients who had sustained acute ischemic stroke. Increased epicardial fat thickness might be a novel risk factor and might enable evaluation of subclinical target-organ damage in these patients. PMID:27303237

  11. The proposed role of plasma NT pro-brain natriuretic peptide in assessing cardiac remodelling in hypertensive African subjects

    PubMed Central

    Ojji, Dike B; Opie, Lionel H; Lecour, Sandrine; Lacerda, Lydia; Sliwa, Karen; Adeyemi, Olusoji M

    2014-01-01

    Summary Aim Although plasma NT-proBNP differentiates hypertension (HT) with or without left ventricular hypertrophy (LVH) from hypertensive heart failure (HHF), most of the published data are based on studies in Western populations. Also, most previous studies did not consider left ventricular (LV) diastolic function and right ventricular (RV) function. We therefore examined the relation between NT-proBNP on LV and RV remodelling in an African hypertensive cohort. Methods Subjects were subdivided into three groups after echocardiography: hypertensives without LVH (HT) (n = 83); hypertensives with LVH (HT+LVH) (n = 50); and those with hypertensive heart failure (HHF) (n = 77). Results Subjects with HHF had significantly higher NT-proBNP levels compared to the HT+LVH group (p < 0.0002). NT-proBNP correlated positively with right atrial area, an indirect measure of RV function. Conclusions NT-proBNP is proposed as a useful biomarker in differentiating hypertension with or without LVH from hypertensive heart failure in black hypertensive subjects. PMID:25629540

  12. N-terminal pro-brain natriuretic peptide measurements in hemodynamically significant patent ductus arteriosus in preterm infants

    PubMed Central

    Alenazi, Shehab Ahmed

    2016-01-01

    Objectives: Evaluate the role of NT-proBNP levels in Preterm neonates suffering from PDA and used as a screening tool for predicting HsPDA and guiding physicians to consider early echocardiographic evaluation. Methods: This is a monocentric prospective blind study which was conducted at Arar Central Hospital, Ar’ar, Saudi Arabia, during the period between Jan 2014 to June 2014. Thirty-three (33) preterm infants born at less than 31 weeks of gestation or weighing less than 1200 g at birth infants were initially enrolled during a 6-month period. Blood samples were collected along with routine blood tests on days 1, 2, 3, and 7 of life for NT-proBNP analysis. Two echocardiographies were systematically performed on day two of life to ascertain about the status of Ductus Arteriosus. Results: The Plasma NT-proBNP levels were high on day one of life and decline from day three to day seven of life except in those infants with significant hsPDA. Plasma NT–proNBP levels on day 2 of infants in the HsPDA group were significantly higher (<0.001) than those in non-HsPDA group. Echocardiogram parameters indicates the significant difference (p<0.002) in Left Atrial and Aortic ratio (LA/AO), Interventricular septum thickness (P<0.03), Left ventricular posterior wall thickness (p<0.05), diastole PDA gradient (p<0.005) between HsPDA and non-HsPDA. Conclusions: Plasma NT-proBNP level peaked during the first few days after birth and declined rapidly within a week. Therefore, its level may have a role as a screening tool to predict HsPDA and provide more information regarding its spontaneous closure or otherwise. PMID:27375693

  13. Preprocedural N‐Terminal Pro‐Brain Natriuretic Peptide (NT‐proBNP) Is Similar to the Mehran Contrast‐Induced Nephropathy (CIN) Score in Predicting CIN Following Elective Coronary Angiography

    PubMed Central

    Liu, Yong; He, Yi‐ting; Tan, Ning; Chen, Ji‐yan; Liu, Yuan‐hui; Yang, Da‐hao; Huang, Shui‐Jin; Ye, Piao; Li, Hua‐long; Ran, Peng; Duan, Chong‐yang; Chen, Shi‐qun; Zhou, Ying‐ling; Chen, Ping‐Yan

    2015-01-01

    Background N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) has been associated with important risk factors for contrast‐induced nephropathy (CIN). However, few studies have investigated the predictive value of NT‐proBNP itself. This study investigated whether levels of preprocedural NT‐proBNP could predict CIN after elective coronary angiography as effectively as the Mehran CIN score. Methods and Results We retrospectively observed 2248 patients who underwent elective coronary angiography. The predictive value of preprocedural NT‐proBNP for CIN was assessed by receiver operating characteristic and multivariable logistic regression analysis. The 50 patients (2.2%) who developed CIN had higher Mehran risk scores (9.5±5.1 versus 4.8±3.8), and higher preprocedural levels of NT‐proBNP (5320±7423 versus 1078±2548 pg/mL, P<0.001). Receiver operating characteristic analysis revealed that NT‐proBNP was not significantly different from the Mehran CIN score in predicting CIN (C=0.7657 versus C=0.7729, P=0.8431). An NT‐proBNP cutoff value of 682 pg/mL predicted CIN with 78% sensitivity and 70% specificity. Multivariable analysis suggested that, after adjustment for other risk factors, NT‐proBNP >682 pg/mL was significantly associated with CIN (odds ratio: 4.007, 95% CI: 1.950 to 8.234; P<0.001) and risk of death (hazard ratio: 2.53; 95% CI: 1.49 to 4.30; P=0.0006). Conclusions Preprocedural NT‐proBNP >682 pg/mL was significantly associated with the risk of CIN and death. NT‐proBNP, like the Mehran CIN score, may be another useful and rapid screening tool for CIN and death risk assessment, identifying subjects who need therapeutic measures to prevent CIN. PMID:25888371

  14. Combination of lung ultrasound (a comet-tail sign) and N-terminal pro-brain natriuretic peptide in differentiating acute heart failure from chronic obstructive pulmonary disease and asthma as cause of acute dyspnea in prehospital emergency setting

    PubMed Central

    2011-01-01

    Introduction We studied the diagnostic accuracy of bedside lung ultrasound (the presence of a comet-tail sign), N-terminal pro-brain natriuretic peptide (NT-proBNP) and clinical assessment (according to the modified Boston criteria) in differentiating heart failure (HF)-related acute dyspnea from pulmonary (chronic obstructive pulmonary disease (COPD)/asthma)-related acute dyspnea in the prehospital setting. Methods Our prospective study was performed at the Center for Emergency Medicine, Maribor, Slovenia, between July 2007 and April 2010. Two groups of patients were compared: a HF-related acute dyspnea group (n = 129) and a pulmonary (asthma/COPD)-related acute dyspnea group (n = 89). All patients underwent lung ultrasound examinations, along with basic laboratory testing, rapid NT-proBNP testing and chest X-rays. Results The ultrasound comet-tail sign has 100% sensitivity, 95% specificity, 100% negative predictive value (NPV) and 96% positive predictive value (PPV) for the diagnosis of HF. NT-proBNP (cutoff point 1,000 pg/mL) has 92% sensitivity, 89% specificity, 86% NPV and 90% PPV. The Boston modified criteria have 85% sensitivity, 86% specificity, 80% NPV and 90% PPV. In comparing the three methods, we found significant differences between ultrasound sign and (1) NT-proBNP (P < 0.05) and (2) Boston modified criteria (P < 0.05). The combination of ultrasound sign and NT-proBNP has 100% sensitivity, 100% specificity, 100% NPV and 100% PPV. With the use of ultrasound, we can exclude HF in patients with pulmonary-related dyspnea who have positive NT-proBNP (> 1,000 pg/mL) and a history of HF. Conclusions An ultrasound comet-tail sign alone or in combination with NT-proBNP has high diagnostic accuracy in differentiating acute HF-related from COPD/asthma-related causes of acute dyspnea in the prehospital emergency setting. Trial registration ClinicalTrials.gov NCT01235182. PMID:21492424

  15. Serum 25-hydroxyvitamin D is not related to cardiac natriuretic peptide in nulliparous and lactating women

    PubMed Central

    Saadi, Hussein F; Nicholls, M Gary; Frampton, Christopher M; Benedict, Sheela; Yasin, Javed

    2009-01-01

    Background Vitamin D deficiency is associated with heightened risk of cardiovascular disease. Potential mechanisms include involvement of vitamin D in regulation of renin-angiotensin system and manufacture and secretion of cardiac natriuretic peptides. Our aim was to document relationships between 25 hydroxyvitamin [25(OH)D] and N-terminal pro B-type natriuretic peptide (NT-proBNP) and plasma renin activity (PRA) levels and to document the effect of vitamin D administration on NT-proBNP and PRA levels in vitamin D deficient subjects. Methods Serum 25(OH)D, parathyroid hormone (PTH), plasma or serum NT-proBNP and PRA levels were measured at baseline in nulliparous and lactating women and after 2 months of oral vitamin D2 (2,000 IU/day or 60,000 IU/month) supplementation to lactating women. Results Baseline levels of 25(OH)D were low (<50 nmol/L) in most women whereas PRA and NT-proBNP levels were within the normal range. There were no significant correlations between baseline 25(OH)D or PTH with NT-proBNP and PRA. Vitamin D administration over a 2-month period in lactating women was associated with a decline in NT-proBNP (by 9.1 ± 2.0 pmol/L; p < 0.001) and PRA (by 0.32 ± 0.17 nmol/L/hr; p = 0.064). However, there were no significant correlations between the changes from baseline in 25(OH)D and either NT-proBNP (r = -0.04, p = 0.8) or PRA (r = -0.04, p = 0.8). Conclusion We found no significant correlations between 25(OH)D or PTH with NT-proBNP and PRA in vitamin D deficient women. Further information is required to clarify the effects of vitamin D administration on cardiac structure and function. PMID:19178708

  16. Metal Organic Frameworks Combining CoFe2O4 Magnetic Nanoparticles as Highly Efficient SERS Sensing Platform for Ultrasensitive Detection of N-Terminal Pro-Brain Natriuretic Peptide.

    PubMed

    He, Yi; Wang, Yue; Yang, Xia; Xie, Shunbi; Yuan, Ruo; Chai, Yaqin

    2016-03-30

    N-terminal pro-brain natriuretic peptide (NT-proBNP) has been demonstrated to be a sensitive and specific biomarker for heart failure (HF). Surface-enhanced Raman spectroscopy (SERS) technology can be used to accurately detect NT-proBNP at an early stage for its advantages of high sensitivity, less wastage and time consumption. In this work, we have demonstrated a new SERS-based immunosensor for ultrasensitive analysis of NT-proBNP by using metal-organic frameworks (MOFs)@Au tetrapods (AuTPs) immobilized toluidine blue as SERS tag. Here, MOFs@AuTPs complexes were utilized to immobilize antibody and Raman probe for their excellent characteristics of high porosity, large surface area, and good biocompatibility which can obviously enhance the fixing amount of biomolecule. To simplify the experimental operation and improve the uniformity of the substrate, Au nanoparticles functionalized CoFe2O4 magnetic nanospheres (CoFe2O4@AuNPs) were further prepared to assemble primary antibody. Through sandwiched antibody-antigen interactions, the immunosensor can produce a strong SERS signal to detect NT-proBNP fast and effectively. With such design, the proposed immunosensor can achieve a large dynamic range of 6 orders of magnitude from 1 fg mL(-1) to 1 ng mL(-1) with a detection limit of 0.75 fg mL(-1). And this newly designed amplification strategy holds high probability for ultrasensitive immunoassay of NT-proBNP. PMID:26953735

  17. Racial Differences in Circulating Natriuretic Peptide Levels: The Atherosclerosis Risk in Communities Study

    PubMed Central

    Gupta, Deepak K; Claggett, Brian; Wells, Quinn; Cheng, Susan; Li, Man; Maruthur, Nisa; Selvin, Elizabeth; Coresh, Josef; Konety, Suma; Butler, Kenneth R; Mosley, Thomas; Boerwinkle, Eric; Hoogeveen, Ron; Ballantyne, Christie M; Solomon, Scott D

    2015-01-01

    Background Natriuretic peptides promote natriuresis, diuresis, and vasodilation. Experimental deficiency of natriuretic peptides leads to hypertension (HTN) and cardiac hypertrophy, conditions more common among African Americans. Hospital-based studies suggest that African Americans may have reduced circulating natriuretic peptides, as compared to Caucasians, but definitive data from community-based cohorts are lacking. Methods and Results We examined plasma N-terminal pro B-type natriuretic peptide (NTproBNP) levels according to race in 9137 Atherosclerosis Risk in Communities (ARIC) Study participants (22% African American) without prevalent cardiovascular disease at visit 4 (1996–1998). Multivariable linear and logistic regression analyses were performed adjusting for clinical covariates. Among African Americans, percent European ancestry was determined from genetic ancestry informative markers and then examined in relation to NTproBNP levels in multivariable linear regression analysis. NTproBNP levels were significantly lower in African Americans (median, 43 pg/mL; interquartile range [IQR], 18, 88) than Caucasians (median, 68 pg/mL; IQR, 36, 124; P<0.0001). In multivariable models, adjusted log NTproBNP levels were 40% lower (95% confidence interval [CI], −43, −36) in African Americans, compared to Caucasians, which was consistent across subgroups of age, gender, HTN, diabetes, insulin resistance, and obesity. African-American race was also significantly associated with having nondetectable NTproBNP (adjusted OR, 5.74; 95% CI, 4.22, 7.80). In multivariable analyses in African Americans, a 10% increase in genetic European ancestry was associated with a 7% (95% CI, 1, 13) increase in adjusted log NTproBNP. Conclusions African Americans have lower levels of plasma NTproBNP than Caucasians, which may be partially owing to genetic variation. Low natriuretic peptide levels in African Americans may contribute to the greater risk for HTN and its sequalae in

  18. Clinical Value of Natriuretic Peptides in Predicting Time to Dialysis in Stage 4 and 5 Chronic Kidney Disease Patients

    PubMed Central

    Sundqvist, Sofia; Larson, Thomas; Cauliez, Bruno; Bauer, Fabrice; Dumont, Audrey; Le Roy, Frank; Hanoy, Mélanie; Fréguin-Bouilland, Caroline; Godin, Michel

    2016-01-01

    Background Anticipating the time to renal replacement therapy (RRT) in chronic kidney disease (CKD) patients is an important but challenging issue. Natriuretic peptides are biomarkers of ventricular dysfunction related to poor outcome in CKD. We comparatively investigated the value of B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) as prognostic markers for the risk of RRT in stage 4 and 5 CKD patients, and in foretelling all-cause mortality and major cardiovascular events within a 5-year follow-up period. Methods Baseline plasma BNP (Triage, Biosite) and NT-proBNP (Elecsys, Roche) were measured at inclusion. Forty-three patients were followed-up during 5 years. Kaplan-Meier analysis, with log-rank testing and hazard ratios (HR), were calculated to evaluate survival without RRT, cardiovascular events or mortality. The independent prognostic value of the biomarkers was estimated in separate Cox multivariate analysis, including estimated glomerular filtration rate (eGFR), creatininemia and comorbidities. Results During the first 12-month follow-up period, 16 patients started RRT. NT-proBNP concentration was higher in patients who reached endpoint (3221 ng/L vs 777 ng/L, p = 0.02). NT-proBNP concentration > 1345 ng/L proved significant predictive value on survival analysis for cardiovascular events (p = 0.04) and dialysis within 60 months follow-up (p = 0.008). BNP concentration > 140 ng/L was an independent predictor of RRT after 12 months follow-up (p<0.005), and of significant predictive value for initiation of dialysis within 60 months follow-up. Conclusions Our results indicate a prognostic value for BNP and NT-proBNP in predicting RRT in stage 4 and 5 CKD patients, regarding both short- and long-term periods. NT-proBNP also proved a value in predicting cardiovascular events. Natriuretic peptides could be useful predictive biomarkers for therapeutic guidance in CKD. PMID:27548064

  19. The prognostic value of the plasma N-terminal pro-brain natriuretic peptide level on all-cause death and major cardiovascular events in a community-based population

    PubMed Central

    Zhu, Qiwei; Xiao, Wenkai; Bai, Yongyi; Ye, Ping; Luo, Leiming; Gao, Peng; Wu, Hongmei; Bai, Jie

    2016-01-01

    Background Despite growing evidence that N-terminal pro-brain natriuretic peptide (NT-proBNP) has an important prognostic value for patients with cardiovascular disease, chronic kidney disease, etc, the prognostic significance of NT-proBNP levels in the general population has not been established. The aim of this study was to evaluate the clinical significance of NT-proBNP in a community population. Methods This is a community-based prospective survey of residents from two communities in Beijing conducted for a routine health status checkup. Out of 1,860 individuals who were eligible for inclusion from 2007 to 2009, 1,499 completed a follow-up and were assessed for the prognostic value of NT-proBNP in 2013. A questionnaire was used for end point events. Anthropometry and blood pressure were measured. Plasma NT-proBNP, creatinine, lipids, and glucose were determined. Results A total of 1,499 subjects with complete data were included in the analysis. Participants were divided into four groups according to baseline NT-proBNP levels (quartile 1, <19.8 pg/mL; quartile 2, 19.8–41.6 pg/mL; quartile 3, 41.7–81.8 pg/mL; quartile 4, ≥81.9 pg/mL). During a median 4.8-year follow-up period, the all-cause mortality rate rose from 0.8% in the lowest concentration NT-proBNP group (<19.8 pg/mL) to 7.8% in the highest NT-proBNP group (≥81.9 pg/mL; P<0.001). The incidence of major adverse cardiovascular events (MACEs) increased from 3.1% in the lowest NT-proBNP group to 18.9% in the highest group (P<0.001). Individuals in the highest NT-proBNP group (≥81.9 pg/mL) were associated with higher risk of all-cause death and MACEs compared with the lowest NT-proBNP group using Kaplan–Meier survival curves and the Cox proportional hazard model after adjusting for age, sex, and traditional risk factors. Conclusion The plasma NT-proBNP level is a strong and independent prognosis factor for all-cause death and MACEs in the community population. The NT-proBNP cut-point for the

  20. Design, Synthesis, and Actions of a Novel Chimeric Natriuretic Peptide: CD-NP

    PubMed Central

    Lisy, Ondrej; Huntley, Brenda K.; McCormick, Daniel J.; Kurlansky, Paul A.; Burnett, John C.

    2008-01-01

    Objectives Our aim was to design, synthesize and test in vivo and in vitro a new chimeric peptide that would combine the beneficial properties of 2 distinct natriuretic peptides with a biological profile that goes beyond native peptides. Background Studies have established the beneficial vascular and antiproliferative properties of C-type natriuretic peptide (CNP). While lacking renal actions, CNP is less hypotensive than the cardiac peptides atrial natriuretic peptide and B-type natriuretic peptide but unloads the heart due to venodilation. Dendroaspis natriuretic peptide is a potent natriuretic and diuretic peptide that is markedly hypotensive and functions via a separate guanylyl cyclase receptor compared with CNP. Methods Here we engineered a novel chimeric peptide CD-NP that represents the fusion of the 22-amino acid peptide CNP together with the 15-amino acid linear C-terminus of Dendroaspis natriuretic peptide. We also determined in vitro in cardiac fibroblasts cyclic guanosine monophosphate-activating and antiproliferative properties of CD-NP. Results Our studies demonstrate in vivo that CD-NP is natriuretic and diuretic, glomerular filtration rate enhancing, cardiac unloading, and renin inhibiting. CD-NP also demonstrates less hypotensive properties when compared with B-type natriuretic peptide. In addition, CD-NP in vitro activates cyclic guanosine monophosphate and inhibits cardiac fibroblast proliferation. Conclusions The current findings advance an innovative design strategy in natriuretic peptide drug discovery and development to create therapeutic peptides with favorable properties that may be preferable to those associated with native natriuretic peptides. PMID:18582636

  1. Novel bifunctional natriuretic peptides as potential therapeutics.

    PubMed

    Dickey, Deborah M; Burnett, John C; Potter, Lincoln R

    2008-12-12

    Synthetic atrial natriuretic peptide (carperitide) and B-type natriuretic peptide (BNP; nesiritide) are used to treat congestive heart failure. However, despite beneficial cardiac unloading properties, reductions in renal perfusion pressures limit their clinical effectiveness. Recently, CD-NP, a chimeric peptide composed of C-type natriuretic peptide (CNP) fused to the C-terminal tail of Dendroaspis natriuretic peptide (DNP), was shown to be more glomerular filtration rate-enhancing than BNP in dogs. However, the molecular basis for the increased responsiveness was not determined. Here, we show that the DNP tail has a striking effect on CNP, converting it from a non-agonist to a partial agonist of natriuretic peptide receptor (NPR)-A while maintaining the ability to activate NPR-B. This effect is specific for human receptors because CD-NP was only a slightly better activator of rat NPR-A due to the promiscuous nature of CNP in this species. Interesting, the DNP tail alone had no effect on any NPR even though it is effective in vivo. To further increase the potency of CD-NP for NPR-A, we converted two different triplet sequences within the CNP ring to their corresponding residues in BNP. Both variants demonstrated increased affinity and full agonist activity for NPR-A, whereas one was as potent as any NPR-A activator known. In contrast to a previous report, we found that DNP binds the natriuretic peptide clearance receptor (NPR-C). However, none of the chimeric peptides bound NPR-C with significantly higher affinity than endogenous ligands. We suggest that bifunctional chimeric peptides represent a new generation of natriuretic peptide therapeutics. PMID:18940797

  2. Novel Bifunctional Natriuretic Peptides as Potential Therapeutics*

    PubMed Central

    Dickey, Deborah M.; Burnett, John C.; Potter, Lincoln R.

    2008-01-01

    Synthetic atrial natriuretic peptide (carperitide) and B-type natriuretic peptide (BNP; nesiritide) are used to treat congestive heart failure. However, despite beneficial cardiac unloading properties, reductions in renal perfusion pressures limit their clinical effectiveness. Recently, CD-NP, a chimeric peptide composed of C-type natriuretic peptide (CNP) fused to the C-terminal tail of Dendroaspis natriuretic peptide (DNP), was shown to be more glomerular filtration rate-enhancing than BNP in dogs. However, the molecular basis for the increased responsiveness was not determined. Here, we show that the DNP tail has a striking effect on CNP, converting it from a non-agonist to a partial agonist of natriuretic peptide receptor (NPR)-A while maintaining the ability to activate NPR-B. This effect is specific for human receptors because CD-NP was only a slightly better activator of rat NPR-A due to the promiscuous nature of CNP in this species. Interesting, the DNP tail alone had no effect on any NPR even though it is effective in vivo. To further increase the potency of CD-NP for NPR-A, we converted two different triplet sequences within the CNP ring to their corresponding residues in BNP. Both variants demonstrated increased affinity and full agonist activity for NPR-A, whereas one was as potent as any NPR-A activator known. In contrast to a previous report, we found that DNP binds the natriuretic peptide clearance receptor (NPR-C). However, none of the chimeric peptides bound NPR-C with significantly higher affinity than endogenous ligands. We suggest that bifunctional chimeric peptides represent a new generation of natriuretic peptide therapeutics. PMID:18940797

  3. Plasma cardiac natriuretic peptide determination as a screening test for the detection of patients with mild left ventricular impairment.

    PubMed Central

    Omland, T.; Aakvaag, A.; Vik-Mo, H.

    1996-01-01

    OBJECTIVE: To determine the usefulness of measuring the cardiac natriuretic peptides, atrial natriuretic factor, N-terminal pro-atrial natriuretic factor, and brain natriuretic peptide, as screening tests for identifying patients with mild left ventricular impairment. DESIGN: Cross-sectional evaluation of the diagnostic accuracy of the cardiac natriuretic peptides. SETTING: Cardiac catheterisation unit, Norwegian central hospital. PATIENTS: A consecutive series of 254 patients undergoing diagnostic left-sided cardiac catheterisation. One hundred and twenty eight of these patients had a history of previous myocardial infarction. MAIN OUTCOME MEASURES: The presence of normal and impaired left ventricular function, as evaluated by logistic regression analysis and estimation of the area under the receiver operating characteristic (ROC) curve (an index of overall diagnostic accuracy). Ventricular function was assessed by the measurement of left ventricular end diastolic pressure and angiographically determined left ventricular ejection fraction. RESULTS: Logistic regression analysis showed that plasma brain natriuretic peptide was the best predictor of increased left ventricular end diastolic pressure (> or = 15 mm Hg) (P < 0.001), decreased left ventricular ejection fraction (< or = 45%) (P < 0.001), and the combination of left ventricular ejection fraction < or = 45% and left ventricular end diastolic pressure > or = 15 mm Hg (P < 0.001). The areas under the ROC function for the detection of left ventricular dysfunction were 0.789 for brain natriuretic peptide, 0.665 for atrial natriuretic factor, and 0.610 for N-terminal pro-atrial natriuretic factor. CONCLUSIONS: Plasma brain natriuretic peptide seemed to be a better indicator of left ventricular function than plasma atrial natriuretic factor or N-terminal pro-atrial natriuretic factor. However, the overall diagnostic accuracy of circulating atrial natriuretic factor, N-terminal pro-atrial natriuretic factor, and

  4. Incremental value of natriuretic peptide measurement in acute decompensated heart failure (ADHF): a systematic review.

    PubMed

    Santaguida, Pasqualina L; Don-Wauchope, Andrew C; Ali, Usman; Oremus, Mark; Brown, Judy A; Bustamam, Amy; Hill, Stephen A; Booth, Ronald A; Sohel, Nazmul; McKelvie, Robert; Balion, Cynthia; Raina, Parminder

    2014-08-01

    The aim of this systematic review was to determine whether B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) independently add incremental value for predicting mortality and morbidity in patients with acute decompensated heart failure (ADHF). Medline(®), Embase™, AMED, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and CINAHL were searched from 1989 to June 2012. We also searched reference lists of included articles, systematic reviews, and the gray literature. Studies were screened for eligibility criteria and assessed for risk of bias. Data were extracted on study design, population demographics, assay cutpoints, prognostic risk prediction model covariates, statistical methods, outcomes, and results. From 183 citations, only seven studies (5 BNP and 2 NT-proBNP) considered incremental value in ADHF subjects admitted to acute care centers. Admission assay levels and length of follow-up varied for BNP studies (31 days to 12 months) and for NT-proBNP studies (25-82 months). All studies presented at least one estimate of incremental value of BNP/NT-proBNP relative to the base prognostic model. Using discrimination or likelihood statistics, these studies consistently showed that BNP or NT-proBNP increased model performance. Three studies used reclassification and model validation computations to establish incremental value; these studies showed less consistency with respect to added value. In conclusion, the literature assessing incremental value of BNP/NT-proBNP in ADHF populations is limited to seven studies evaluating only mortality outcomes and at moderate risk of bias. Although there were differences in the base risk prediction models, assay cutpoints, and lengths of follow-up, there was consistency in BNP/NT-proBNP adding incremental value in prediction models in ADHF patients. PMID:25052418

  5. Pro Atrial Natriuretic Peptide (1-30) and 6-keto PGF1α Activity Affects Na(+) Homeostasis in Non-modulating Hypertension.

    PubMed

    Sanchez, Ramiro A; Gilbert, Bernardo H; Masnatta, Lucas; Giannone, Carlos; Pesiney, Carlina; Ramirez, Agustin J

    2015-01-01

    Non-modulating hypertension (NMHT) is a high renin subtype of salt sensitive hypertension, which fails to achieve renal vasodilatation and a correct Na(+) handling during sodium load. We investigate, in MHT and NMHT, the role of ANP, the renin-angiotensin system and PgI2, in the renal sodium handling mechanisms. After 10 days of low (20mmol.L) or after 72hs of high (250mmol.L) sodium intake, 13 NMHT (34±5y; 9 male) and 13 MHT (32±4y; 10male) were studied. Pro-ANP (1-30) PgI2, PRA and total exchangeable Na(+)24 (ENa(+)) were measured. Under low sodium intake, PRA (4.2±0.5ng.ml.h; p<0.05) and Pro-ANP (78.6±2pg/ml, p<0.05) were higher than in NMHT under (3.1±0.4ng.ml.h and 69.8±3 pg/ml). After 72h of high Na(+) intake, Pro-ANP (1-30) increased significantly only in MHT (82.1±3pg/ml, p<0.05). PgI2, under low sodium intake (1.83±0.2pg/24h), increased in MHT after 72h under high sodium (2.58±0.5pg/ 24h, p<0.02). Under low sodium diet, PgI2 (2.16±0.11pg/24h) was as higher in NMHT, as in MHT. After 72h under high Na+ intake, it failed to show any change (2.61±0.36 pg/24h; p=ns). A significant correlation between variations in ENa(+) and mean blood pressure (r=0.50, p<0.01), variations in Pro-ANP (1-30) values and ENa(+) in MHT (r=0.95; p<0.001) while a negative correlation between ENa(+) variations and ENa(+) (r=0.81, p<0.05) was observed in NMHT. ENa(+) variations were only significantly related to variations in FF in MHT. Thus, in NMHT, there is an unbalanced relationship between vasonstrictor and vasodilator mediators. From these, as an extrarenal homeostatic mediator, ANP seems to play an important role to compensate the altered renal sodium handling. PMID:26028240

  6. Evaluation of New Diagnostic Biomarkers in Pediatric Sepsis: Matrix Metalloproteinase-9, Tissue Inhibitor of Metalloproteinase-1, Mid-Regional Pro-Atrial Natriuretic Peptide, and Adipocyte Fatty-Acid Binding Protein

    PubMed Central

    Alqahtani, Mashael F.; Smith, Craig M.; Weiss, Scott L.; Dawson, Susan; Ralay Ranaivo, Hantamalala; Wainwright, Mark S.

    2016-01-01

    Elevated plasma concentrations of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), mid-regional pro-atrial natriuretic peptide (mrProANP), and adipocyte fatty-acid-binding proteins (A-FaBPs) have been investigated as biomarkers for sepsis or detection of acute neurological injuries in adults, but not children. We carried out a single-center, prospective observational study to determine if these measures could serve as biomarkers to identify children with sepsis. A secondary aim was to determine if these biomarkers could identify children with neurologic complications of sepsis. A total of 90 patients ≤ 18 years-old were included in this study. 30 with severe sepsis or septic shock were compared to 30 age-matched febrile and 30 age-matched healthy controls. Serial measurements of each biomarker were obtained, beginning on day 1 of ICU admission. In septic patients, MMP9-/TIMP-1 ratios (Median, IQR, n) were reduced on day 1 (0.024, 0.004–0.174, 13), day 2 (0.020, 0.002–0.109, 10), and day 3 (0.018, 0.003–0.058, 23) compared with febrile (0.705, 0.187–1.778, 22) and healthy (0.7, 0.4–1.2, 29) (p< 0.05) controls. A-FaBP and mrProANP (Median, IQR ng/mL, n) were elevated in septic patients compared to control groups on first 2 days after admission to the PICU (p <0.05). The area under the curve (AUC) for MMP-9/TIMP-1 ratio, mrProANP, and A-FaBP to distinguish septic patients from healthy controls were 0.96, 0.99, and 0.76, respectively. MMP-9/TIMP-1 ratio was inversely and mrProANP was directly related to PIM-2, PELOD, and ICU and hospital LOS (p<0.05). A-FaBP level was associated with PELOD, hospital and ICU length of stay (p<0.05). MMP-9/TIMP-1 ratio associated with poor Glasgow Outcome Score (p<0.05). A-FaBP levels in septic patients with neurological dysfunction (29.3, 17.2–54.6, 7) were significantly increased compared to septic patients without neurological dysfunction (14.6, 13.3–20.6, 11). MMP-9/TIMP-1 ratios

  7. Useulness of B Natriuretic Peptides and Procalcitonin in Emergency Medicine.

    PubMed

    Delerme, S; Chenevier-Gobeaux, C; Doumenc, B; Ray, P

    2008-01-01

    Congestive heart failure (CHF) is the main cause of acute dyspnea in patients presented to an emergency department (ED), and it is associated with high morbidity and mortality. B-type natriuretic peptide (BNP) is a polypeptide, released by ventricular myocytes directly proportional to wall tension, for lowering renin-angiotensin-aldosterone activation. For diagnosing CHF, both BNP and the biologically inactive NT-proBNP have similar accuracy. Threshold values are higher in elderly population, and in patients with renal dysfunction. They might have also a prognostic value. Studies demonstrated that the use of BNP or NT-proBNP in dyspneic patients early in the ED reduced the time to discharge, total treatment cost. BNP and NT-proBNP should be available in every ED 24 hours a day, because literature strongly suggests the beneficial impact of an early appropriate diagnosis and treatment in dyspneic patients.Etiologic diagnosis of febrile patients who present to an ED is complex and sometimes difficult. However, new evidence showed that there are interventions (including early appropriate antibiotics), which could reduce mortality rate in patients with sepsis. For diagnosing sepsis, procalcitonin (PCT) is more accurate than C-reactive protein. Thus, because of its excellent specificity and positive predictive value, an elevated PCT concentration (higher than 0.5 ng/mL) indicates ongoing and potentially severe systemic infection, which needs early antibiotics (e.g. meningitis). In lower respiratory tract infections, CAP or COPD exacerbation, PCT guidance reduced total antibiotic exposure and/or antibiotic treatment duration. PMID:19578505

  8. [Brain natriuretic peptide].

    PubMed

    La Villa, G; Lazzeri, C; Fronzaroli, C; Franchi, F; Gentilini, P

    1995-01-01

    Brain natriuretic peptide (BNP) is a cardiac hormone with a spectrum of activities quite similar to those of atrial natriuretic peptide (ANP), including diuretic, natriuretic, hypotensive and smooth muscle relaxant activities. These effects are due to the stimulation of guanylate cyclase-linked natriuretic peptide receptors, leading to an increase in cyclic GMP concentration in target cells. BNP has a lower affinity than ANP for C (clearance) receptors, and is less susceptible to degradation by neutral endopeptidase-24.11, resulting in a longer half-life. In the kidney, BNP increases the glomerular filtration rate and inhibits sodium reabsorption in the distal tubule. It also inhibits the release of renin and aldosterone. Unlike ANP, produced by the atria, BNP is mainly synthesized and released into circulation by the left ventricle and is therefore influenced by stimuli involving this cardiac chamber, such as an increase in arterial pressure, left ventricular hypertrophy and dilation. Plasma BNP levels are very low in healthy subjects, and respond modestly, although significantly to physiological stimuli such as changes in posture or sodium intake. In contrast, plasma BNP concentrations increase in disease states such as cirrhosis with ascites, hypertension, chronic renal failure, acute myocardial infarction and congestive heart failure. In the latter condition, plasma BNP concentration is a reliable prognostic index. Evidence obtained by administering BNP to healthy subjects and hypertensive patients suggests that BNP, at physiological and pathophysiological plasma concentrations, markedly influences cardiovascular homeostasis, mainly due to its effects on sodium excretion and the renin-aldosterone axis. PMID:8718658

  9. [Measurement of natriuretic peptides in heart failure: the good laboratory and clinical practice].

    PubMed

    Kovács, L Gábor; Nyolczas, Noémi; Habon, Tamás; Sepp, Róbert; Piroth, Zsolt; Hajas, Ágota; Boncz, Imre; Tomcsányi, János; Kappelmayer, János; Merkely, Béla

    2015-08-01

    Cardiac natriuretic peptides (BNP, NT-proBNP) play a pivotal role in cardiovascular homeostasis, mainly due to their roles in vasodilatation, natriuresis, diuresis and due to their antiproliferative properties. Proper measurement of the natriuretic peptide levels may help differentiate between respiratory and cardiac forms of dyspnea, diagnose early forms of heart failure, evaluate severity of heart failure (prognosis) and monitor the efficacy of therapy. In many countries natriuretic peptide levels are being used as one of the earliest diagnostics tools to evaluate the involvement of the heart. Current theoretical and clinical data confirm the importance of natriuretic peptides in routine healthcare. These roles are clearly described in international recommendations and guidelines. In the current review the authors discuss the problems of the measurement of natriuretic peptides in Hungary, including several aspects related to laboratory medicine, cardiology and health economy. PMID:26211747

  10. Contribution of Kv7 channels to natriuretic peptide mediated vasodilation in normal and hypertensive rats.

    PubMed

    Stott, Jennifer B; Barrese, Vincenzo; Jepps, Thomas A; Leighton, Emma V; Greenwood, Iain A

    2015-03-01

    The Kv7 family of voltage-gated potassium channels are expressed within the vasculature where they are key regulators of vascular tone and mediate cAMP-linked endogenous vasodilator responses, a pathway that is compromised in hypertension. However, the role of Kv7 channels in non-cAMP-linked vasodilator pathways has not been investigated. Natriuretic peptides are potent vasodilators, which operate primarily through the activation of a cGMP-dependent signaling pathway. This study investigated the putative role of Kv7 channels in natriuretic peptide-dependent relaxations in the vasculature of normal and hypertensive animals. Relaxant responses of rat aorta to both atrial and C-type natriuretic peptides and the nitric oxide donor sodium nitroprusside were impaired by the Kv7 blocker linopirdine (10 μmol/L) but not by the Kv7.1-specific blocker HMR1556 (10 μmol/L) and other K(+) channel blockers. In contrast, only the atrial natriuretic peptide response was sensitive to linopirdine in the renal artery. These Kv7-mediated responses were attenuated in arteries from hypertensive rats. Quantitative polymerase chain reaction showed that A- and B-type natriuretic peptide receptors were expressed at high levels in the aorta and renal artery from normal and spontaneously hypertensive rats. This study provides the first evidence that natriuretic peptide responses are impaired in hypertension and that recruitment of Kv7 channels is a key component of natriuretic peptide-dependent vasodilations. PMID:25547342

  11. Natriuretic Peptides and Cardiometabolic Health.

    PubMed

    Gupta, Deepak K; Wang, Thomas J

    2015-01-01

    Natriuretic peptides are cardiac-derived hormones with a range of protective functions, including natriuresis, diuresis, vasodilation, lusitropy, lipolysis, weight loss, and improved insulin sensitivity. Their actions are mediated through membrane-bound guanylyl cyclases that lead to production of the intracellular second-messenger cyclic guanosine monophosphate. A growing body of evidence demonstrates that genetic and acquired deficiencies of the natriuretic peptide system can promote hypertension, cardiac hypertrophy, obesity, diabetes mellitus, the metabolic syndrome, and heart failure. Clinically, natriuretic peptides are robust diagnostic and prognostic markers, and augmenting natriuretic peptides is a target for therapeutic strategies in cardiometabolic disease. This review will summarize current understanding and highlight novel aspects of natriuretic peptide biology. PMID:26103984

  12. Testing for BNP and NT-proBNP in the diagnosis and prognosis of heart failure.

    PubMed Central

    Balion, C; Santaguida, P L; Hill, S; Worster, A; McQueen, M; Oremus, M; McKelvie, R; Booker, L; Fagbemi, J; Reichert, S; Raina, P

    2006-01-01

    OBJECTIVES The purpose of this systematic review was to evaluate BNP and NT-proBNP to: (a) identify determinants, (b) establish their diagnostic performance in heart failure (HF) patients, (c) determine their predictive ability with respect to mortality and other cardiac endpoints, and (d) determine their value in monitoring HF treatment. DATA SOURCES MEDLINE, EMBASE, CINAHL, Cochrane Central, and AMED from 1989 to February 2005 were searched for primary studies. REVIEW METHODS Standard systematic review methodology, including meta-analysis, was employed. All study designs were included. Eligibility criteria included English-only studies and restricted the number of test methods to maximize generalizability. Outcomes for prognosis were limited to mortality and specific cardiac events. Further specific criteria were developed for each research question. RESULTS Determinants: There were 103 determinants identified including age, gender, disease, treatment, as well as biochemical and physiological measures. Few studies reported independent associations and of those that did age, female gender and creatinine levels were positively associated with BNP and NT-proBNP. DIAGNOSIS Pooled sensitivity and specificity values were 94 and 66 percent for BNP and 92 and 65 percent for NT-proBNP; there was minimal difference among settings (emergency, specialized clinics, and primary care). B-type natriuretic peptides also added independent diagnostic information above traditional measures for HF. PROGNOSIS Both BNP and NT-proBNP were found to be independent predictors of mortality and other cardiac composite endpoints in patients with risk of coronary artery disease (CAD) (risk estimate range = 1.10 to 5.40), diagnosed CAD (risk estimate range = 1.50 to 3.00), and diagnosed HF patients (risk estimate range = 2.11 to 9.35). With respect to screening, the AUC values (range = 0.57 to 0.88) suggested poor performance. Monitoring Treatment: Studies showed therapy reduced BNP and NT-pro

  13. Changes in Serum Natriuretic Peptide Levels after Percutaneous Closure of Small to Moderate Ventricular Septal Defects

    PubMed Central

    Kaya, Yuksel; Akdemir, Ramazan; Gunduz, Huseyin; Murat, Sani; Bulut, Orhan; Kocayigit, İbrahim; Vatan, M. Bulent; Cakar, M. Akif; Yeter, Ekrem; Kilic, Harun; Agac, Mustafa Tarik; Acar, Zeydin

    2012-01-01

    Background. B-type natriuretic peptide has been shown to be a very sensitive and specific marker of heart failure. In this study, we aimed to investigate the effect of percutaneous closure of ventricular septal defects with Amplatzer septal occluders on brain natriuretic peptide levels. Methods. Between 2008 and 2011, 23 patients underwent successfully percutaneous ventricular septal defect closure in 4 cardiology centers. Brain natriuretic peptide levels were measured in nine patients (4 male, mean ages were 25.3 ± 14.3) who underwent percutaneous closure with Amplatzer occluders for membranous or muscular ventricular septal defects were enrolled in the study. Brain natriuretic peptide levels were measured one day before and one month after the closure. Patients were evaluated clinically and by echocardiography one month after the procedure. Results. Percutaneous closures of ventricular septal defects were successfully performed in all patients. There was not any significant adverse event in patients group during followup. Decrease in brain natriuretic peptide levels after closure were statistically significant (97.3 ± 78.6 versus 26.8 ± 15.6, P = 0.013). Conclusion. Brain Natriuretic Peptide levels are elevated in patients with ventricular septal defects as compared to controls. Percutaneous closure of Ventricular Septal Defect with Amplatzer occluders decreases the BNP levels. PMID:22629130

  14. Circulatory fate of the atrial natriuretic peptide precursor

    SciTech Connect

    Lewicki, J.; Hilliker, S.; Borden, L.; Hancock, N.; Scarborough, R.; Vlasuk, G.

    1986-03-05

    The atrial natriuretic peptides (ANP) are stored in atria principally as a 126 amino acid precursor form (proANP). Although a predominant circulating form of the ANP's is apparently 28 amino acids in length (ANP(1-28)), smaller quantities of proANP can be detected in plasma by radioimmunoassay. This raises the possibility that ANP(1-28) may be derived from proANP within the circulation. To test this possibility, HPLC was used to assess the conversion of recombinant /sup 35/S-cysteine-labelled proANP (/sup 35/S-proANP) to /sup 35/S-ANP(1-28) following incubation with biological fluids. It was determined that incubation with rat or human serum readily converts /sup 35/S-proANP to /sup 35/S-ANP(1-28), however, this conversion did not occur upon incubation with plasma. Furthermore, /sup 35/S-proANP infused into the circulation of the rat was quite stable metabolically. No /sup 35/S-ANP(1-28) or related low molecular weight ANP's could be detected in the circulation for up to two hours following /sup 35/S-proANP administration. These data imply that proANP is not converted significantly to ANP(1-28) in the circulation of the rat. Thus, processing of proANP to ANP(1-28) probably occurs within the atrium or during release of the peptides from atrium.

  15. B-type natriuretic peptide for assessment of haemodynamically significant patent ductus arteriosus in premature infants

    PubMed Central

    Mine, Kenji; Ohashi, Atsushi; Tsuji, Shoji; Nakashima, Jun-ichi; Hirabayashi, Masato; Kaneko, Kazunari

    2013-01-01

    Aim: Haemodynamically significant patent ductus arteriosus (hsPDA) is frequently observed in premature infants. This study was conducted to explore whether the blood BNP can be a valuable biomarker to assess the necessity of treatment for hsPDA in premature infants. Methods: Serial measurements of the blood BNP were performed during the first 5 days of life in premature infants with hsPDA (Group I) and those without hsPDA (Group N). The definition of the hsPDA was the PDA requiring treatment, such as indomethacin administration and/or surgical ligation. Results: Forty-six subjects were enrolled. Compared with Group N, Group I showed significantly higher level of blood BNP at postnatal 24–96 h and demonstrated the peak value at postnatal 24–48 h. With the ROC curve using the data at postnatal 24–48 h in Group I, we deduced the predictive value of 250 pg/mL of blood BNP for indomethacin treatment. Similarly, with the ROC curve using the maximal value of blood BNP within the first 5 days of life, the predictive value of 2000 pg/mL for surgical ligation was deduced. Conclusions: Blood BNP during early postnatal period can be a useful biomarker to assess the necessity of treatment for hsPDA in premature infants. PMID:23611593

  16. Natriuretic peptides in cardiovascular diseases: current use and perspectives

    PubMed Central

    Volpe, Massimo; Rubattu, Speranza; Burnett, John

    2014-01-01

    The natriuretic peptides (NPs) family, including atrial, B-type, and C-type NPs, is a group of hormones possessing relevant haemodynamic and anti-remodelling actions in the cardiovascular (CV) system. Due to their diuretic, natriuretic, vasorelaxant, anti-proliferative, and anti-hypertrophic effects, they are involved in the pathogenic mechanisms leading to major CV diseases, such as heart failure (HF), coronary artery disease, hypertension and left ventricular hypertrophy, and cerebrovascular accidents. Blood levels of NPs have established predictive value in the diagnosis of HF, as well as for its prognostic stratification. In addition, they provide useful clinical information in hypertension and in both stable and unstable coronary artery disease. Structural abnormalities of atrial natriuretic peptide gene (NPPA), as well as genetically induced changes in circulating levels of NPs, have a pathogenic causal link with CV diseases and represent emerging markers of CV risk. Novel NP-based therapeutic strategies are currently under advanced clinical development, as they are expected to contribute to the future management of hypertension and HF. The present review provides a current appraisal of NPs’ clinical implications and a critical perspective of the potential therapeutic impact of pharmacological manipulation of this class of CV hormones. PMID:24227810

  17. Performance of BNP and NT-proBNP for diagnosis of heart failure in primary care patients: a systematic review.

    PubMed

    Booth, Ronald A; Hill, Stephen A; Don-Wauchope, Andrew; Santaguida, P Lina; Oremus, Mark; McKelvie, Robert; Balion, Cynthia; Brown, Judy A; Ali, Usman; Bustamam, Amy; Sohel, Nazmul; Raina, Parminder

    2014-08-01

    National and international guidelines have been published recommending the use of natriuretic peptides as an aid to the diagnosis of heart failure (HF) in acute settings; however, few specific recommendations exist for governing the use of these peptides in primary care populations. To summarize the available data relevant to the diagnosis of HF in primary care patient population, we systematically reviewed the literature to identify original articles that investigated the diagnostic accuracy of B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) in primary care settings. The search yielded 25,864 articles in total: 12 investigating BNP and 20 investigating NT-proBNP were relevant to our objective and included in the review. QUADAS-2 and GRADE were used to assess the quality of the included articles. Diagnostic data were pooled based on three cutpoints: lowest and optimal, as chosen by study authors, and manufacturers' suggested. The effect of various determinants (e.g., age, gender, BMI, and renal function) on diagnostic performance was also investigated. Pooled sensitivity and specificity of BNP and NT-proBNP using the lowest [0.85 (sensitivity) and 0.54 (specificity)], optimal (0.80 and 0.61), and manufacturers' (0.74 and 0.67) cutpoints showed good performance for diagnosing HF. Similar performance was seen for NT-proBNP: lowest (0.90 and 0.50), optimal (0.86 and 0.58), and manufacturers' (0.82 and 0.58) cutpoints. Overall, we rated the strength of evidence as high because further studies will be unlikely to change the estimates diagnostic performance. PMID:24969534

  18. Dendroaspis natriuretic peptide binds to the natriuretic peptide clearance receptor

    SciTech Connect

    Johns, Douglas G. . E-mail: Douglas.G.Johns@gsk.com; Ao, Zhaohui; Heidrich, Bradley J.; Hunsberger, Gerald E.; Graham, Taylor; Payne, Lisa; Elshourbagy, Nabil; Lu, Quinn; Aiyar, Nambi; Douglas, Stephen A.

    2007-06-22

    Dendroaspis natriuretic peptide (DNP) is a newly-described natriuretic peptide which lowers blood pressure via vasodilation. The natriuretic peptide clearance receptor (NPR-C) removes natriuretic peptides from the circulation, but whether DNP interacts with human NPR-C directly is unknown. The purpose of this study was to test the hypothesis that DNP binds to NPR-C. ANP, BNP, CNP, and the NPR-C ligands AP-811 and cANP(4-23) displaced [{sup 125}I]-ANP from NPR-C with pM-to-nM K {sub i} values. DNP displaced [{sup 125}I]-ANP from NPR-C with nM potency, which represents the first direct demonstration of binding of DNP to human NPR-C. DNP showed high pM affinity for the GC-A receptor and no affinity for GC-B (K {sub i} > 1000 nM). DNP was nearly 10-fold more potent than ANP at stimulating cGMP production in GC-A expressing cells. Blockade of NPR-C might represent a novel therapeutic approach in augmenting the known beneficial actions of DNP in cardiovascular diseases such as hypertension and heart failure.

  19. Analytical evaluation of the Dade Behring Dimension RxL automated N-Terminal proBNP (NT-proBNP) method and comparison with the Roche Elecsys 2010.

    PubMed

    Di Serio, Francesca; Ruggieri, Vincenzo; Varraso, Lucia; De Sario, Rosalisa; Mastrorilli, Angela; Pansini, Nicola

    2005-01-01

    Methods to quantify B-type natriuretic peptide (BNP) and N-terminal-propeptide (NT-proBNP) in plasma or serum samples are well established. We assessed the analytical performance of the Dimension RxL NT-proBNP method (Dade-Behring). Evaluation of different sample types was carried out. Controls and heparin plasma pools were used to determine the detection limit, precision, and linearity. Sample stability and the effect of interfering substances on the NT-proBNP concentrations were evaluated. Agreement between Dimension RxL and Elecsys 2010 (Roche Diagnostics) NT-proBNP methods was assessed. The influence of age and sex on NT-proBNP concentrations was evaluated in healthy subjects. Heparin plasma should be the matrix of choice. The detection limit was 2.0 ng/L. The total imprecision was 2.6-3.6% for concentrations from 231 to 9471 ng/L; mean NT-proBNP concentrations of 21 and 15 ng/L were associated with coefficients of variation of 9.9% and 14.7%, respectively. The method was linear up to 32,650 ng/L. There was no effect of temperature, freeze-thaw cycles and interfering substances. A bias was detected when Dimension RxL and Elecsys 2010 NT-proBNP methods were compared. Age and sex were significantly and independently related to NT-proBNP concentrations. The Dimension RxL NT-proBNP method, like the Elecsys 2010, is suitable for routine use in the diagnosis of heart failure. PMID:16232094

  20. New insight into the role of NT-proBNP in alcoholic liver cirrhosis as a noninvasive marker of esophageal varices

    PubMed Central

    Ljubičić, Neven; Gomerčić, Marija; Zekanović, Dražen; Bodrožić-, Tomislava; Džakić; Đuzel, Ana

    2012-01-01

    Aim To investigate the association between plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and formation of esophageal varices. Methods Thirty-five patients with alcoholic cirrhosis were divided into three groups according to the Child-Pugh classification: grade A (n = 11, 32%), B (n = 12, 34%), and C (n = 12, 34%). System hemodynamic parameters were measured using sphygmomanometry, electrocardiography, and echocardiography. NT-proBNP was analyzed by using an electrochemiluminiscence sandwich immunoassay. Results The presence of esophageal varices was associated with a higher serum NT-proBNP level, with a cut-off value of >101 pg/mL (sensitivity, 87.60% and specificity, 72.73%; P < 0.001). Conclusions NT-proBNP was found to be a marker of the presence of esophageal varices, but not a marker of progression of liver cirrhosis. In cirrhotic patients, NT-proBNP value >101 pg/mL was shown to be a valuable noninvasive parameter in predicting the presence of varices. PMID:22911531

  1. [Natriuretic peptides. History of discovery, chemical structure, mechanism of action and the removal routes. Basis of diagnostic and therapeutic use].

    PubMed

    Stryjewski, Piotr J; Nessler, Bohdan; Cubera, Katarzyna; Nessler, Jadwiga

    2013-01-01

    Natriuretic peptides (NP) are the group of proteins synthesized and secreted by the mammalian heart. All the NP are synthesized from prohormones and have 17-amino acid cyclic structures containing two cysteine residues linked by internal disulphide bond. They are characterized by a wide range of actions, mainly through their membrane receptors. The NP regulate the water and electrolyte balance, blood pressure through their diuretic, natriuretic, and relaxating the vascular smooth muscles effects. They also affect the endocrine system and the nervous system. The neurohormonal regulation of blood circulation results are mainly based on antagonism with renin--angiotensin--aldosterone system. The NP representatives are: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), urodilatine and (DNP) Dendroaspis natriuretic peptide, not found in the human body. According to the guidelines of the European Society of Cardiology determination of NT-proBNP level have found a use in the diagnosis of acute and chronic heart failure, risk stratification in acute coronary syndromes and pulmonary embolism. There are reports found in the literature, that demonstrate the usefulness of NT-proBNP determination in valvular, atrial fibrillation, and syncopes. Recombinant human ANP--Carperitid and BNP--Nesiritid, have already found a use in the adjunctive therapy of dyspnea in acute heart failure. PMID:24167949

  2. Evidence for a novel natriuretic peptide receptor that prefers brain natriuretic peptide over atrial natriuretic peptide.

    PubMed Central

    Goy, M F; Oliver, P M; Purdy, K E; Knowles, J W; Fox, J E; Mohler, P J; Qian, X; Smithies, O; Maeda, N

    2001-01-01

    Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) exert their physiological actions by binding to natriuretic peptide receptor A (NPRA), a receptor guanylate cyclase (rGC) that synthesizes cGMP in response to both ligands. The family of rGCs is rapidly expanding, and it is plausible that there might be additional, as yet undiscovered, rGCs whose function is to provide alternative signalling pathways for one or both of these peptides, particularly given the low affinity of NPRA for BNP. We have investigated this hypothesis, using a genetically modified (knockout) mouse in which the gene encoding NPRA has been disrupted. Enzyme assays and NPRA-specific Western blots performed on tissues from wild-type mice demonstrate that ANP-activated cGMP synthesis provides a good index of NPRA protein expression, which ranges from maximal in adrenal gland, lung, kidney, and testis to minimal in heart and colon. In contrast, immunoreactive NPRA is not detectable in tissues isolated from NPRA knockout animals and ANP- and BNP-stimulatable GC activities are markedly reduced in all mutant tissues. However, testis and adrenal gland retain statistically significant, high-affinity responses to BNP. This residual response to BNP cannot be accounted for by natriuretic peptide receptor B, or any other known mammalian rGC, suggesting the presence of a novel receptor in these tissues that prefers BNP over ANP. PMID:11513736

  3. Cardiovascular biomarker midregional proatrial natriuretic peptide during and after preeclamptic pregnancies.

    PubMed

    Sugulle, Meryam; Herse, Florian; Hering, Lydia; Mockel, Martin; Dechend, Ralf; Staff, Anne Cathrine

    2012-02-01

    Preeclampsia is associated with increased risk of cardiovascular disease. Midregional proatrial natriuretic peptide (MR-proANP), a precursor of the atrial natriuretic peptide, is a biomarker for cardiovascular disease. We obtained plasma from 184 pregnant women in gestational weeks 24 to 42 (normotensive pregnancies: n=77, preeclampsia: n=107), from 25 of these women at 5 to 8 years after index pregnancy (normotensive pregnancies: n=11, preeclampsia: n=14), and from 49 normotensive, nonpregnant women and analyzed them by immunoassay for MR-proANP. To investigate potential sources, placental and decidual atrial natriuretic peptide mRNA expression levels were analyzed by quantitative real-time PCR in 21 normotensive and 23 preeclamptic pregnancies, as well as in human heart and kidney samples. For further confirmation, we measured circulating MR-proANP and performed expression studies in a transgenic rat model for preeclampsia. MR-proANP was significantly elevated in maternal plasma in preeclampsia compared with normotensive pregnancies (135 versus 56 pmol/L; P<0.001). However, 5 to 8 years after pregnancy, there was no difference (formerly preeclamptic women versus formerly normotensive in pregnancy: 53 versus 49 pmol/L; P=0.5). Our preeclamptic rat model confirmed the acute MR-proANP differences between preeclamptic and normotensive pregnancies (10.9±1.9 versus 4.3±0.3 pmol/L; P=0.05). Atrial natriuretic peptide expression was high in the heart but negligible in the uteroplacental unit in both normotensive humans and rats, whereas expression in maternal and fetal hearts in the preeclamptic rats was significantly increased, compared with controls. MR-proANP is a serviceable biomarker in preeclampsia, both in humans and a rat model, probably reflecting cardiovascular hemodynamic stress. PMID:22184318

  4. Natriuretic peptides and their therapeutic potential.

    PubMed

    Cho, Y; Somer, B G; Amatya, A

    1999-01-01

    Natriuretic peptides are a group of naturally occurring substances that act in the body to oppose the activity of the renin-angiotensin system. There are three major natriuretic peptides: atrial natriuretic peptide (ANP), which is synthesized in the atria; brain natriuretic peptide (BNP), which is synthesized in the ventricles; and C-type natriuretic peptide (CNP), which is synthesized in the brain. Both ANP and BNP are released in response to atrial and ventricular stretch, respectively, and will cause vasorelaxation, inhibition of aldosterone secretion in the adrenal cortex, and inhibition of renin secretion in the kidney. Both ANP and BNP will cause natriuresis and a reduction in intravascular volume, effects amplified by antagonism of antidiuretic hormone (ADH). The physiologic effects of CNP are different from those of ANP and BNP. CNP has a hypotensive effect, but no significant diuretic or natriuretic actions. Three natriuretic peptide receptors (NPRs) have been described that have different binding capacities for ANP, BNP, and CNP. Removal of the natriuretic peptides from the circulation is affected mainly by binding to clearance receptors and enzymatic degradation in the circulation. Increased blood levels of natriuretic peptides have been found in certain disease states, suggesting a role in the pathophysiology of those diseases, including congestive heart failure (CHF), systemic hypertension, and acute myocardial infarction. The natriuretic peptides also serve as disease markers and indicators of prognosis in various cardiovascular conditions. The natriuretic peptides have been used in the treatment of disease, with the most experience with intravenous BNP in the treatment of CHF. Another pharmacologic approach being used is the inhibition of natriuretic peptide metabolism by neutral endopeptidase (NEP) inhibitor drugs. The NEP inhibitors are currently being investigated as treatments for CHF and systemic hypertension. PMID:11720638

  5. Vascular effects and electrolyte homeostasis of the natriuretic peptide isolated from Crotalus oreganus abyssus (North American Grand Canyon rattlesnake) venom.

    PubMed

    Da Silva, S L; Dias-Junior, C A; Baldasso, P A; Damico, D C S; Carvalho, B M A; Garanto, A; Acosta, G; Oliveira, E; Albericio, F; Soares, A M; Marangoni, S; Resende, R R

    2012-08-01

    Crotalus oreganus abyssus is a rattlesnake that is usually found in the Grand Canyon, United States of America. Knowledge regarding the composition of C. o. abyssus venom is scarce. New natriuretic peptides (NPs) have been isolated and characterized from the venoms of members of the Crotalinae family. The NP family comprises three members, ANP (atrial natriuretic peptide), BNP (b-type natriuretic peptide) and CNP (c-type natriuretic peptide), and has an important role in blood pressure regulation and electrolyte homeostasis. The aim of the present study was to characterize a novel natriuretic-like peptide (Coa_NP2), isolated from C. o. abyssus venom. The Coa_NP2 presents an average molecular mass of 3419.88Da (theoretical average molecular mass 3418.94Da, monoisotopic molecular mass 3416.66Da and theoretical PI 7.78) and its amino acid sequence presents the loop region that is characteristic of natriuretic peptides. The peptide has 32 amino acids and its complete sequence is SYGISSGCFGLKLDRIGTMSGLGCWRLLQDSP. Coa_NP2 is a natriuretic peptide of the ANP/BNP-like family, since the carboxyterminal region of CNP has its own NP domain. We demonstrate, herein, that Coa_NP2 produces a dose-dependent decrease in mean arterial pressure in rats, followed by significant increases in concentrations of markers of nitric oxide formation measured in the plasma and vasorelaxation in a thoracic aortic ring bath. The structural and biological aspects confirm Coa_NP2 as a new natriuretic peptide, isolated from snake venom. PMID:22617223

  6. A systematic review of BNP and NT-proBNP in the management of heart failure: overview and methods.

    PubMed

    Oremus, Mark; McKelvie, Robert; Don-Wauchope, Andrew; Santaguida, Pasqualina L; Ali, Usman; Balion, Cynthia; Hill, Stephen; Booth, Ronald; Brown, Judy A; Bustamam, Amy; Sohel, Nazmul; Raina, Parminder

    2014-08-01

    B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) levels are increased in persons with heart failure (HF); low levels of these peptides rule out HF. We systematically reviewed the literature to assess the use of BNP and NT-proBNP in the diagnosis, prognosis, and treatment for HF. We also examined the biological variation of these peptides in persons with and without HF. We searched Medline, Embase, AMED, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and CINAHL for English-language studies published between January 1989 and June 2012. Supplemental searches involved the gray literature and the reference lists of included studies. Trained reviewers used standardized forms to screen articles for inclusion in the review and to extract data from included papers. We examined the risk of bias with QUADAS-2 for diagnosis studies, the Hayden criteria for prognosis studies, and the Jadad scale for treatment studies. We assessed the strength of evidence in four domains (risk of bias, consistency, directness, and precision) for the diagnosis and treatment studies. Results were reported as narrative syntheses. Additional meta-analyses were conducted for the diagnosis studies. Three hundred ten articles passed through screening and were included in the review. One hundred four articles applied to diagnostic accuracy, 190 papers pertained to prognosis, and nine articles addressed BNP- or NT-proBNP-guided treatment. Each individual paper in this series reports, summarizes, and discusses the evidence regarding diagnosis, prognosis, or treatment. PMID:24953975

  7. Parallel evolution of circulating FABP4 and NT-proBNP in heart failure patients

    PubMed Central

    2013-01-01

    Background Circulating adipocyte fatty acid-binding protein (FABP4) levels are considered to be a link between obesity, insulin resistance, diabetes, and cardiovascular (CV) diseases. In vitro, FABP4 has exhibited cardiodepressant activity by suppressing cardiomyocyte contraction. We have explored the relationship between FABP4 and the N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP) as a clinical parameter of heart failure (HF). Methods We included 179 stable HF patients who were referred to a specialized HF unit, 108 of whom were prospectively followed for up to 6 months. A group of 163 non-HF patients attending a CV risk unit was used as the non-HF control group for the FABP4 comparisons. Results In the HF patients, FABP4 and NT-proBNP were assayed, along with a clinical and functional assessment of the heart at baseline and after 6 months of specialized monitoring. The FABP4 levels were higher in the patients with HF than in the non-HF high CV risk control group (p<0.001). The FABP4 levels were associated with the NT-proBNP levels in patients with HF (r=0.601, p<0.001), and this association was stronger in the diabetic patients. FABP4 was also associated with heart rate and the results of the 6-minute walk test. After the follow-up period, FABP4 decreased in parallel to NT-proBNP and to the clinical parameters of HF. Conclusions FABP4 is associated with the clinical manifestations and biomarkers of HF. It exhibits a parallel evolution with the circulating levels of NT-proBNP in HF patients. PMID:23642261

  8. The diagnostic accuracy of the natriuretic peptides in heart failure: systematic review and diagnostic meta-analysis in the acute care setting

    PubMed Central

    Roberts, Emmert; Dworzynski, Katharina; Al-Mohammad, Abdallah; Cowie, Martin R; McMurray, John J V; Mant, Jonathan

    2015-01-01

    Objectives To determine and compare the diagnostic accuracy of serum natriuretic peptide levels (B type natriuretic peptide, N terminal probrain natriuretic peptide (NTproBNP), and mid-regional proatrial natriuretic peptide (MRproANP)) in people presenting with acute heart failure to acute care settings using thresholds recommended in the 2012 European Society of Cardiology guidelines for heart failure. Design Systematic review and diagnostic meta-analysis. Data sources Medline, Embase, Cochrane central register of controlled trials, Cochrane database of systematic reviews, database of abstracts of reviews of effects, NHS economic evaluation database, and Health Technology Assessment up to 28 January 2014, using combinations of subject headings and terms relating to heart failure and natriuretic peptides. Eligibility criteria for selecting studies Eligible studies evaluated one or more natriuretic peptides (B type natriuretic peptide, NTproBNP, or MRproANP) in the diagnosis of acute heart failure against an acceptable reference standard in consecutive or randomly selected adults in an acute care setting. Studies were excluded if they did not present sufficient data to extract or calculate true positives, false positives, false negatives, and true negatives, or report age independent natriuretic peptide thresholds. Studies not available in English were also excluded. Results 37 unique study cohorts described in 42 study reports were included, with a total of 48 test evaluations reporting 15 263 test results. At the lower recommended thresholds of 100 ng/L for B type natriuretic peptide and 300 ng/L for NTproBNP, the natriuretic peptides have sensitivities of 0.95 (95% confidence interval 0.93 to 0.96) and 0.99 (0.97 to 1.00) and negative predictive values of 0.94 (0.90 to 0.96) and 0.98 (0.89 to 1.0), respectively, for a diagnosis of acute heart failure. At the lower recommended threshold of 120 pmol/L, MRproANP has a sensitivity ranging from 0.95 (range 0

  9. Chamber-dependent circadian expression of cardiac natriuretic peptides.

    PubMed

    Goetze, Jens Peter; Georg, Birgitte; Jørgensen, Henrik L; Fahrenkrug, Jan

    2010-02-25

    Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) have important local functions within the myocardium, where they protect against accelerated fibrosis. As circadian expression of cardiac natriuretic peptides could be of importance in local cardiac protection against disease, we examined the diurnal changes of the mRNAs encoding ANP, BNP, and their common receptor NPR-A in atrial and ventricular myocardium. Forty eight mice were killed at the following ZT times: 4, 8, 12, 16, 20, and 24, where ZT designates Zeitgeber; ZT 0 corresponds to lights ON and ZT 12 corresponds to lights OFF. Eight animals (4 males and 4 females) were included at each time point. Another 48 animals were killed during the second cycle of dark/dark (designated Circadian Time or CT: CT 4, CT 8, CT 12, CT 16, CT 20, and CT 24). The cellular contents of the clock genes Per1 and Bmal1 as well as ANP, BNP, and their common receptor (NPR-A) were determined using RT-PCR. Per1 and Bmal1 mRNA contents oscillated in antiphase in both atrial and ventricular regions, where Bmal1 mRNA peaked 12h out of phase relative to Per1 mRNA. ANP and NPR-A atrial mRNA contents revealed borderline significant diurnal changes, whereas ventricular BNP mRNA contents exhibited pronounced oscillation during constant darkness with nadir at CT 12 (P<0.0001). In conclusion, we report a chamber-dependent circadian profile of cardiac BNP mRNA contents, which is not paralleled by the related ANP gene. Our findings suggest that the BNP mRNA pattern could be associated with increased cardiac susceptibility and response to disease. PMID:20035806

  10. Brain Natriuretic Peptide: It's Not About the Brain or Just Another Smart Polypeptide--It's About the Heart.

    PubMed

    Carella, Dominick M

    2015-01-01

    Brain natriuretic peptide (BNP) is a cardiac hormone with diuretic, natriuretic, and vasodilator properties. Measurement of plasma B-type natriuretic peptide concentrations is increasingly used to aid diagnosis, assess prognosis, and tailor treatment in adults with congestive heart failure. Recent studies suggest that the peptide is also useful in pediatric patients. The diagnostic role of plasma BNP in neonates admitted to the NICU has shown promise as an aid in diagnosis in neonates with signs of congenital heart disease; as a biomarker of bronchopulmonary dysplasia, patent ductus arteriosus, and persistent pulmonary hypertension of the newborn; a predictive biomarker of the response to indomethacin in preterm infants; and, more significantly, in acute heart failure. PMID:26803017

  11. Pre-admission NT-proBNP improves diagnostic yield and risk stratification – the NT-proBNP for EValuation of dyspnoeic patients in the Emergency Room and hospital (BNP4EVER) study

    PubMed Central

    Januzzi, James L; Medvedovski, Margarita; Sharist, Moshe; Shochat, Michael; Ashkar, Jalal; Peschansky, Pavel; Haim, Shmuel Bar; Blondheim, David S; Glikson, Michael; Shotan, Avraham

    2012-01-01

    Background: Amino-terminal pro-B-type natriuretic peptide (NT-proBNP) level is useful to diagnose or exclude acutely decompensated heart failure (ADHF) in dyspnoeic patients presenting to the emergency department (ED). Aim: To evaluate the impact of ED NT-proBNP testing on admission, length of stay (LOS), discharge diagnosis and long-term outcome. Methods: Dyspnoeic patients were randomized in the ED to NT-proBNP testing. Admission and discharge diagnoses, and outcomes were examined. Results: During 17 months, 470 patients were enrolled and followed for 2.0±1.3 years. ADHF likelihood, determined at study conclusion by validated criteria, established ADHF diagnosis as unlikely in 86 (17%), possible in 120 (24%), and likely in 293 (59%) patients. The respective admission rates in these subgroups were 80, 91, and 96%, regardless of blinding, and 61.9% of blinded vs. 74.5% of unblinded ADHF-likely patients were correctly diagnosed at discharge (p=0.029), with similar LOS. 2-year mortality within subgroups was unaffected by test, but was lower in ADHF-likely patients with NT-proBNP levels below median (5000 pg/ml) compared with those above median (p=0.002). Incidence of recurrent cardiac events tracked NT-proBNP levels. Conclusion: ED NT-proBNP testing did not affect admission, LOS, 2-year survival, or recurrent cardiac events among study patients but improved diagnosis at discharge, and allowed risk stratification even within the ADHF-likely group. (ClinicalTrials.gov#NCT00271128) PMID:24062895

  12. Genome-wide association and Mendelian randomization study of NT-proBNP in patients with acute coronary syndrome.

    PubMed

    Johansson, Åsa; Eriksson, Niclas; Lindholm, Daniel; Varenhorst, Christoph; James, Stefan; Syvänen, Ann-Christine; Axelsson, Tomas; Siegbahn, Agneta; Barratt, Bryan J; Becker, Richard C; Himmelmann, Anders; Katus, Hugo A; Steg, Philippe Gabriel; Storey, Robert F; Wallentin, Lars

    2016-04-01

    N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a strong predictor of mortality in coronary artery disease and is widely employed as a prognostic biomarker. However, a causal relationship between NT-proBNP and clinical endpoints has not been established. We have performed a genome-wide association and Mendelian randomization study of NT-proBNP. We used a discovery set of 3740 patients from the PLATelet inhibition and patient Outcomes (PLATO) trial, which enrolled 18 624 patients with acute coronary syndrome (ACS). A further set of 5492 patients, from the same trial, was used for replication. Genetic variants at two novel loci (SLC39A8 and POC1B/GALNT4) were associated with NT-proBNP levels and replicated together with the previously known NPPB locus. The most significant SNP (rs198389, pooled P = 1.07 × 10(-15)) in NPPB interrupts an E-box consensus motif in the gene promoter. The association in SLC39A8 is driven by a deleterious variant (rs13107325, pooled P = 5.99 × 10(-10)), whereas the most significant SNP in POC1B/GALNT4 (rs11105306, pooled P = 1.02 × 10(-16)) is intronic. The SLC39A8 SNP was associated with higher risk of cardiovascular (CV) death (HR = 1.39, 95% CI: 1.08-1.79, P = 0.0095), but the other loci were not associated with clinical endpoints. We have identified two novel loci to be associated with NT-proBNP in patients with ACS. Only the SLC39A8 variant, but not the NPPB variant, was associated with a clinical endpoint. Due to pleotropic effects of SLC39A8, these results do not suggest that NT-proBNP levels have a direct effect on mortality in ACS patients. PLATO Clinical Trial Registration: www.clinicaltrials.gov; NCT00391872. PMID:26908625

  13. The natriuretic peptides and cardiometabolic health

    PubMed Central

    Gupta, Deepak K.; Wang, Thomas J.

    2016-01-01

    Natriuretic peptides are cardiac-derived hormones with a range of protective functions, including natriuresis, diuresis, vasodilation, lusitropy, lipolysis, weight loss, and improved insulin sensitivity. The actions are mediated through membrane bound guanylyl cyclases that lead to production of the intracellular second-messenger cGMP. A growing body of evidence demonstrates that genetic and acquired deficiencies of the natriuretic peptide system can promote hypertension, cardiac hypertrophy, obesity, diabetes mellitus, the metabolic syndrome, and heart failure. Clinically, natriuretic peptides are robust diagnostic and prognostic markers and augmenting natriuretic peptides is a target for therapeutic strategies in cardio-metabolic disease. This review will summarize current understanding and highlight novel aspects of natriuretic peptide biology. PMID:26103984

  14. B-type stars in eclipsing binaries

    NASA Astrophysics Data System (ADS)

    Ratajczak, Milena; Pigulski, Andrzej

    2016-07-01

    B-type stars in eclipsing binary systems are unique astrophysical tools to test several aspects of stellar evolution. Such objects can be used e.g. to determine the masses of Beta Cephei variable stars, as well as help to place tighter constraints on the value of the convective core overshooting parameter α. Both precise photometry and high-resolution spectroscopy with high SNR are required to achieve these goals, but since many of the targets are bright enough, the challenge is fair. Following this assumption, we shall explain how we plan to examine both the aforementioned aspects of stellar evolution using observations of B-type stars obtained with a wide range of spectrographs, as well as BRITE-Constellation satellites.

  15. Natriuretic peptide testing for heart failure therapy guidance in the inpatient and outpatient setting.

    PubMed

    Green, Sandy M; Green, Jamie A; Januzzi, James L

    2009-01-01

    Acutely destabilized heart failure is one of the most common diagnoses in the modern health care system. It has high hospital readmission rates and significant short-, medium-, and long-term mortality, likely due to misdiagnosis or failure to assess adequate treatment before discharge. Cardiac biomarkers such as B-type natriuretic peptide and its amino terminal cleavage equivalent N-terminal fragment have rapidly become one of the key tools in the diagnosis and guidance of heart failure therapy. In this article, we shall review the data on the current use of the natriuretic peptides for the diagnosis, prognosis, and management of heart failure in both the outpatient and inpatient settings. PMID:19300043

  16. Localization of corin and atrial natriuretic peptide expression in human renal segments.

    PubMed

    Dong, Liang; Wang, Hao; Dong, Ningzheng; Zhang, Ce; Xue, Boxin; Wu, Qingyu

    2016-09-01

    Atrial natriuretic peptide (ANP)-mediated natriuretic response is a well-established cardiac endocrine function. Corin is a transmembrane protease that activates ANP in the heart. Corin expression has been detected in non-cardiac tissues including the kidney. Here we examined corin, pro-ANP/ANP and natriuretic peptide receptor-A (NPR-A) expression in human renal segments. By immunostaining and in situ hybridization, we found similar corin, pro-ANP/ANP and NPR-A protein and mRNA expression in human renal segments. The expression was most abundant in the proximal convoluted tubules and the medullary connecting ducts. In the proximal tubules, corin protein was present in the apical membrane region underneath the brush border where the ANP-degrading protease neprilysin was abundant. These results suggest that corin-mediated pro-ANP activation may occur in renal segments and that locally produced ANP may act in an autocrine manner to regulate sodium and water reabsorption in situ Our results also point to the proximal convoluted tubules as a major site for local ANP action. Such a renal corin/ANP autocrine mechanism may differ from the cardiac corin/ANP endocrine mechanism in regulating sodium homoeostasis under physiological and pathological conditions. PMID:27343265

  17. Natriuretic Hormones in Brain Function

    PubMed Central

    Hodes, Anastasia; Lichtstein, David

    2014-01-01

    Natriuretic hormones (NH) include three groups of compounds: the natriuretic peptides (ANP, BNP and CNP), the gastrointestinal peptides (guanylin and uroguanylin), and endogenous cardiac steroids. These substances induce the kidney to excrete sodium and therefore participate in the regulation of sodium and water homeostasis, blood volume, and blood pressure (BP). In addition to their peripheral functions, these hormones act as neurotransmitters or neuromodulators in the brain. In this review, the established information on the biosynthesis, release and function of NH is discussed, with particular focus on their role in brain function. The available literature on the expression patterns of each of the NH and their receptors in the brain is summarized, followed by the evidence for their roles in modulating brain function. Although numerous open questions exist regarding this issue, the available data support the notion that NH participate in the central regulation of BP, neuroprotection, satiety, and various psychiatric conditions, including anxiety, addiction, and depressive disorders. In addition, the interactions between the different NH in the periphery and the brain are discussed. PMID:25506340

  18. Structure, signaling mechanism and regulation of the natriuretic peptide receptor guanylate cyclase.

    SciTech Connect

    Misono, K. S.; Philo, J. S.; Arakawa, T.; Ogata, C. M.; Qiu, Y.; Ogawa, H.; Young, H. S.

    2011-06-01

    Atrial natriuretic peptide (ANP) and the homologous B-type natriuretic peptide are cardiac hormones that dilate blood vessels and stimulate natriuresis and diuresis, thereby lowering blood pressure and blood volume. ANP and B-type natriuretic peptide counterbalance the actions of the renin-angiotensin-aldosterone and neurohormonal systems, and play a central role in cardiovascular regulation. These activities are mediated by natriuretic peptide receptor-A (NPRA), a single transmembrane segment, guanylyl cyclase (GC)-linked receptor that occurs as a homodimer. Here, we present an overview of the structure, possible chloride-mediated regulation and signaling mechanism of NPRA and other receptor GCs. Earlier, we determined the crystal structures of the NPRA extracellular domain with and without bound ANP. Their structural comparison has revealed a novel ANP-induced rotation mechanism occurring in the juxtamembrane region that apparently triggers transmembrane signal transduction. More recently, the crystal structures of the dimerized catalytic domain of green algae GC Cyg12 and that of cyanobacterium GC Cya2 have been reported. These structures closely resemble that of the adenylyl cyclase catalytic domain, consisting of a C1 and C2 subdomain heterodimer. Adenylyl cyclase is activated by binding of G{sub s}{alpha} to C2 and the ensuing 7{sup o} rotation of C1 around an axis parallel to the central cleft, thereby inducing the heterodimer to adopt a catalytically active conformation. We speculate that, in NPRA, the ANP-induced rotation of the juxtamembrane domains, transmitted across the transmembrane helices, may induce a similar rotation in each of the dimerized GC catalytic domains, leading to the stimulation of the GC catalytic activity.

  19. BNP and NT-proBNP as prognostic markers in persons with acute decompensated heart failure: a systematic review.

    PubMed

    Santaguida, Pasqualina L; Don-Wauchope, Andrew C; Oremus, Mark; McKelvie, Robert; Ali, Usman; Hill, Stephen A; Balion, Cynthia; Booth, Ronald A; Brown, Judy A; Bustamam, Amy; Sohel, Nazmul; Raina, Parminder

    2014-08-01

    A systematic review was undertaken to examine the evidence for B-type natriuretic peptides (BNP and NT-proBNP) as independent predictors of mortality, morbidity, or combined mortality and morbidity outcomes in persons with acute decompensated heart failure (ADHF). Electronic databases (Medline(®), Embase™, AMED, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and CINAHL) were searched from 1989 to June 2012. Reference lists of included articles, systematic reviews, and the gray literature were also searched. English language studies were eligible if they included subjects with ADHF and measured BNP/NT-proBNP using FDA approved assays. Standardized forms were used to select studies, extract data, and assess risk of bias. Seventy-nine studies, ranging over followup intervals from 14 days to 7 years, evaluating levels of BNP (n = 38), NT-proBNP (n = 35), or both (n = 6) were eligible. The majority of studies predicted mortality outcomes for admission BNP/NT-proBNP levels, with fewer studies evaluating serial, change from admission, or discharge levels. In general, higher levels of admission BNP or NT-proBNP predicted greater risk for all outcomes. Decreased levels post-admission predicted decreased risk. Overall, these studies were rated as having moderate risk of bias. This systematic review shows that BNP and NT-proBNP are independent predictors of mortality (all-cause and cardiovascular) in ADHF despite different cutpoints, time intervals, and prognostic models. Findings for morbidity and composite outcomes were less frequently evaluated and showed inconsistency. Further research is required to assess cutpoints for admission, serial measurements, change following admission, and discharge levels to assist clinical decision-making. PMID:25062653

  20. Natriuretic peptide receptors in the fetal rat.

    PubMed

    Brown, J; Zuo, Z

    1995-08-01

    In vitro autoradiography of rat fetuses from embryonic days 12-19 (E12-E19) showed widespread high-affinity specific binding sites for natriuretic peptides. The sites on E16 somites avidly bound C-type natriuretic peptide [CNP-(1-22)] as well as C-ANP, a synthetic ligand that selects the C-type natriuretic peptide receptor (NPR-C). Most somitic binding sites had high affinity for atrial natriuretic peptide [ANP-(1-28)], confirming their resemblance to NPR-C. A few had a lower apparent affinity for ANP-(1-28), suggesting that they might be NPR-B. CNP-(1-22) was more powerful than ANP-(1-28) as an agonist of guanosine 3',5'-cyclic monophosphate production in somites, and ATP augmented the action of CNP-(1-22). These observations further suggest the presence of NPR-B. However, with cross-linking of 3-[125I]iodo-0-tyrosyl rat CNP-(1-22) to somitic membranes followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, only a single 64-kDa binding protein was detected under reducing conditions. This is not consistent with intact approximately 120-kDa NPR-B. In vitro autoradiography of the binding of natriuretic peptides to E16 liver implied the presence of NPR-A and NPR-C-like receptors. Hepatic guanosine 3',5'-cyclic monophosphate production was most powerfully stimulated by ANP-(1-28), as expected for NPR-A. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis also identified NPR-A and NPR-C-like proteins in E16 hepatic membranes. Thus different NPRs are expressed by specific fetal tissues. This may be developmentally significant. PMID:7653543

  1. Novel biomarkers in acute heart failure: MR-pro-adrenomedullin.

    PubMed

    Peacock, W Frank

    2014-10-01

    First isolated from human pheochromocytoma cells, adrenomedullin (ADM) is a peptide hormone with natriuretic, vasodilatory, and hypotensive effects mediated by cyclic adenosine monophosphate (cAMP), nitric oxide, and renal prostaglandin systems. ADM expression occurs in many tissues and organ systems, including cardiovascular, renal, pulmonary, cerebrovascular, gastrointestinal, and endocrine tissues where it acts as a circulating hormone and a local autocrine and paracrine hormone. ADM plasma concentrations are increased in hypertension, chronic renal disease, and heart failure. As ADM is unstable in vitro, it is necessary to measure its mid-regional pro-hormone fragment, the levels of which correspond to ADM concentration (MR-proADM). The prognostic potential of MR-proADM was recently demonstrated in the Biomarkers in Acute Heart Failure (BACH) trial. In this trial of 568 acute heart failure patients, MR-proADM was superior to both brain natriuretic peptide (BNP) and NT-proBNP in predicting mortality within 14 days. MR-proADM also provided significant additive incremental predictive value for 90-day mortality when added to BNP and NT-proBNP. PMID:24756062

  2. FEATURE B, TYPE 1 PILLBOX, SOUTH AND WEST SIDES, VIEW ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    FEATURE B, TYPE 1 PILLBOX, SOUTH AND WEST SIDES, VIEW FACING NORTH-NORTHEAST. - Naval Air Station Barbers Point, Shore Pillbox Complex-Type 1 Pillbox, Along shoreline, seaward of Coral Sea Road, Ewa, Honolulu County, HI

  3. C-type natriuretic peptide signalling drives homeostatic effects in human chondrocytes.

    PubMed

    Peake, N J; Bader, D L; Vessillier, S; Ramachandran, M; Salter, D M; Hobbs, A J; Chowdhury, T T

    2015-10-01

    Signals induced by mechanical loading and C-type natriuretic peptide (CNP) represent chondroprotective routes that may potentially prevent osteoarthritis (OA). We examined whether CNP will reduce hyaluronan production and export via members of the multidrug resistance protein (MRP) and diminish pro-inflammatory effects in human chondrocytes. The presence of interleukin-1β (IL-1β) increased HA production and export via MRP5 that was reduced with CNP and/or loading. Treatment with IL-1β conditioned medium increased production of catabolic mediators and the response was reduced with the hyaluronan inhibitor, Pep-1. The induction of pro-inflammatory cytokines by the conditioned medium was reduced by CNP and/or Pep-1, αCD44 or αTLR4 in a cytokine-dependent manner, suggesting that the CNP pathway is protective and should be exploited further. PMID:26307537

  4. Structure, signaling mechanism and regulation of natriuretic peptide receptor-guanylate cyclase

    PubMed Central

    Misono, Kunio S.; Philo, John S.; Arakawa, Tsutomu; Ogata, Craig M.; Qiu, Yue; Ogawa, Haruo; Young, Howard S.

    2011-01-01

    Summary Atrial natriuretic peptide (ANP) and homologous B-type natriuretic peptide (BNP) are cardiac hormones that dilate blood vessels and stimulate natriuresis and diuresis, thereby lowering blood pressure and blood volume. ANP and BNP counterbalance the actions of the renin-angiotensin-aldosterone and neurohormonal systems, and play a central role in cardiovascular regulation. These activities are mediated by the A-type natriuretic peptide receptor (NPRA), a single transmembrane segment, guanylate cyclase (GC) linked receptor that occurs as a homodimer. Here we present an overview of the structure, possible chloride-mediated regulation, and signaling mechanism of the NPRA and other receptor-GCs. Earlier, we determined the crystal structures of the NPRA extracellular domain with and without bound ANP. Their structural comparison has revealed a novel ANP-induced rotation mechanism occurring in the juxtamembrane region that apparently triggers transmembrane signal transduction. More recently, the crystal structures of the dimerized catalytic domain of green algae GC Cyg12 and that of cyanobacter GC Cya2 have been reported. These structures closely resemble that of the adenylate cyclase catalytic domain consisting of C1 and C2 subdomain heterodimer. AC is activated by binding of Gsα to C2 and ensuing 7° rotation of C1 around an axis parallel to the central cleft, thereby inducing the heterodimer into a catalytically active conformation. We speculate that, in the NPRA, the ANP-induced rotation of the juxtamembrane domains, transmitted across the transmembrane helices, may induce a similar rotation in each of the dimerized GC catalytic domains, leading to the stimulation of the GC catalytic activity. PMID:21375693

  5. [ATRIAL AND BRAIN NATRIURETIC PEPTIDES OF CARDIAC MUSCLE CELLS IN POSTREPERFUSION PERIOD IN RATS].

    PubMed

    Bugrova, M L

    2016-01-01

    Accumulation and release of atrial and brain natriuretic peptides (ANP and BNP) in right atrial cardiac muscle cells has been investigated in rats after 60 minutes and 60 days after the reperfusion start. The total ischemia was simulated by the method of V. G. Korpachev. Immunocytochemical localization of peptides in cardiomyocytes was performed in ultrathin sections using polyclonal antibodies. The intensity of accumulation/excretion of ANP and BNP were analyzed by the method of counting the number of granules (A- and B-types) with immunoreactive labels in 38 x 38 mkm2 visual fields in transmission electron microscope Morgagni 268D (FEI). The results were assessed using Mann-Whitney U-test (p < 0.05). After 60 minutes and 60 days post-reperfusion period, we detected an increase in the synthesis and release of ANP and BNP. The reaction of BNP was more pronounced than ANP. This is due to the fact that ANP is the main hormone of the natriuretic peptide system involved in the regulation of blood pressure in normal conditions, while BNP is the principal regulator of pressure in cardiovascular pathology. PMID:27228659

  6. Cocaine-associated increase of atrial natriuretic peptides: an early predictor of cardiac complications in cocaine users?

    PubMed Central

    Casartelli, Alessandro; Dacome, Lisa; Tessari, Michela; Pascali, Jennifer; Bortolotti, Federica; Trevisan, Maria Teresa; Bosco, Oliviero; Cristofori, Patrizia; Tagliaro, Franco

    2014-01-01

    Objective Cocaine is known to produce life-threatening cardiovascular complications, and the investigation of the causes of death may be challenging in forensic medicine. The increasing knowledge of the cardiac function biomarkers and the increasing sensitivity of assays provide new tools in monitoring the cardiac life-threatening pathological conditions and in the sudden death investigation in chronic abusers. In this work, cardiac dysfunction was assessed in an animal model by measuring troponin I and natriuretic peptides as biomarkers, and considering other standard endpoints used in preclinical toxicology studies. Methods Lister Hooded rats were treated with cocaine in chronic self-administration studies. Troponin I (cTnI) and atrial natriuretic peptide (ANP) were evaluated at different time points and heart weight and histopathology were assessed at the end of the treatment period. Furthermore, cocaine and its main metabolites were measured in the rat fur to assess rats’ cocaine exposure. All the procedures and endpoints considered were designed to allow an easy and complete translation from the laboratory animals to human beings, and the same approach was also adopted with a group of 10 healthy cocaine abuse volunteers with no cardiac pathologies. Results Cardiac troponin I values were unaffected, and ANP showed an increasing trend with time in all cocaine-treated animals considered. Similarly, in the healthy volunteers, no changes were observed in troponin serum levels, whereas the N-terminal brain natriuretic pro-peptide (NT proBNP) showed variations comparable with the changes observed in rats. Conclusions In conclusion, natriuretic peptides could represent an early indicator of heart dysfunction liability in chronic cocaine abusers. PMID:27326180

  7. Near Infrared Spectroscopy of B-type Asteroids

    NASA Astrophysics Data System (ADS)

    Yang, Bin; Jewitt, D.

    2009-09-01

    Most small bodies in the Solar system possess optical colors that are either redder than, or comparable to, the Solar colors in the wavelength region from 0.4 to 0.9 µm. However, a small fraction, about 1 out of every 23 asteroids, is found to be bluer than the Sun. These rare, blue asteroids, of which 2 Pallas is the largest and most famous example, are classified as B-types in the Bus spectral taxonomy. The paucity of B-types already makes these objects interesting. Moreover, several meteor shower-associated asteroids (e.g. 3200 Phaethon, 2005 UD) are found to be blue in the optical. Furthermore, the available optical spectra of the main belt comets 133P and 176P are similar to those of the B-type asteroids. However, B-type asteroids remain largely unexamined as a group and our knowledge of their properties is correspondingly limited. For this reason, we undertook a focused, spectroscopic study of 20 B-type asteroids using the 3-meter IRTF telescope atop Mauna Kea, Hawaii. The spectra show that optically similar B-type asteroids are spectrally diverse in the near infrared. We find that the negative optical spectral slope is due to the presence of a broad absorption band centered near 1.0 µm. Amongst the meteorites, the best spectral analogs are found in the unusual CI and CM carbonaceous chondrites. The 1.0 µm absorption feature in several objects is very well matched by the reflection spectrum of magnetite. We will present our observations of the 20 B-type asteroids and discuss the possible aqueous alteration history of these objects.

  8. Natriuretic peptide-guided management in heart failure.

    PubMed

    Chioncel, Ovidiu; Collins, Sean P; Greene, Stephen J; Ambrosy, Andrew P; Vaduganathan, Muthiah; Macarie, Cezar; Butler, Javed; Gheorghiade, Mihai

    2016-08-01

    Heart failure is a clinical syndrome that manifests from various cardiac and noncardiac abnormalities. Accordingly, rapid and readily accessible methods for diagnosis and risk stratification are invaluable for providing clinical care, deciding allocation of scare resources, and designing selection criteria for clinical trials. Natriuretic peptides represent one of the most important diagnostic and prognostic tools available for the care of heart failure patients. Natriuretic peptide testing has the distinct advantage of objectivity, reproducibility, and widespread availability.The concept of tailoring heart failure management to achieve a target value of natriuretic peptides has been tested in various clinical trials and may be considered as an effective method for longitudinal biomonitoring and guiding escalation of heart failure therapies with overall favorable results.Although heart failure trials support efficacy and safety of natriuretic peptide-guided therapy as compared with usual care, the relationship between natriuretic peptide trajectory and clinical benefit has not been uniform across the trials, and certain subgroups have not shown robust benefit. Furthermore, the precise natriuretic peptide value ranges and time intervals of testing are still under investigation. If natriuretic peptides fail to decrease following intensification of therapy, further work is needed to clarify the optimal pharmacologic approach. Despite decreasing natriuretic peptide levels, some patients may present with other high-risk features (e.g. elevated troponin). A multimarker panel investigating multiple pathological processes will likely be an optimal alternative, but this will require prospective validation.Future research will be needed to clarify the type and magnitude of the target natriuretic peptide therapeutic response, as well as the duration of natriuretic peptide-guided therapy in heart failure patients. PMID:27110656

  9. C-type natriuretic peptide modulates quorum sensing molecule and toxin production in Pseudomonas aeruginosa.

    PubMed

    Blier, Anne-Sophie; Veron, Wilfried; Bazire, Alexis; Gerault, Eloïse; Taupin, Laure; Vieillard, Julien; Rehel, Karine; Dufour, Alain; Le Derf, Franck; Orange, Nicole; Hulen, Christian; Feuilloley, Marc G J; Lesouhaitier, Olivier

    2011-07-01

    Pseudomonas aeruginosa coordinates its virulence expression and establishment in the host in response to modification of its environment. During the infectious process, bacteria are exposed to and can detect eukaryotic products including hormones. It has been shown that P. aeruginosa is sensitive to natriuretic peptides, a family of eukaryotic hormones, through a cyclic nucleotide-dependent sensor system that modulates its cytotoxicity. We observed that pre-treatment of P. aeruginosa PAO1 with C-type natriuretic peptide (CNP) increases the capacity of the bacteria to kill Caenorhabditis elegans through diffusive toxin production. In contrast, brain natriuretic peptide (BNP) did not affect the capacity of the bacteria to kill C. elegans. The bacterial production of hydrogen cyanide (HCN) was enhanced by both BNP and CNP whereas the production of phenazine pyocyanin was strongly inhibited by CNP. The amount of 2-heptyl-4-quinolone (HHQ), a precursor to 2-heptyl-3-hydroxyl-4-quinolone (Pseudomonas quinolone signal; PQS), decreased after CNP treatment. The quantity of 2-nonyl-4-quinolone (HNQ), another quinolone which is synthesized from HHQ, was also reduced after CNP treatment. Conversely, both BNP and CNP significantly enhanced bacterial production of acylhomoserine lactone (AHL) [e.g. 3-oxo-dodecanoyl-homoserine lactone (3OC12-HSL) and butanoylhomoserine lactone (C4-HSL)]. These results correlate with an induction of lasI transcription 1 h after bacterial exposure to BNP or CNP. Concurrently, pre-treatment of P. aeruginosa PAO1 with either BNP or CNP enhanced PAO1 exotoxin A production, via a higher toxA mRNA level. At the same time, CNP led to elevated amounts of algC mRNA, indicating that algC is involved in C. elegans killing. Finally, we observed that in PAO1, Vfr protein is essential to the pro-virulent effect of CNP whereas the regulator PtxR supports only a part of the CNP pro-virulent activity. Taken together, these data reinforce the hypothesis that during

  10. C-type natriuretic peptide modulates quorum sensing molecule and toxin production in Pseudomonas aeruginosa

    PubMed Central

    Blier, Anne-Sophie; Veron, Wilfried; Bazire, Alexis; Gerault, Eloïse; Taupin, Laure; Vieillard, Julien; Rehel, Karine; Dufour, Alain; Le Derf, Franck; Orange, Nicole; Hulen, Christian; Feuilloley, Marc G. J.

    2011-01-01

    Pseudomonas aeruginosa coordinates its virulence expression and establishment in the host in response to modification of its environment. During the infectious process, bacteria are exposed to and can detect eukaryotic products including hormones. It has been shown that P. aeruginosa is sensitive to natriuretic peptides, a family of eukaryotic hormones, through a cyclic nucleotide-dependent sensor system that modulates its cytotoxicity. We observed that pre-treatment of P. aeruginosa PAO1 with C-type natriuretic peptide (CNP) increases the capacity of the bacteria to kill Caenorhabditis elegans through diffusive toxin production. In contrast, brain natriuretic peptide (BNP) did not affect the capacity of the bacteria to kill C. elegans. The bacterial production of hydrogen cyanide (HCN) was enhanced by both BNP and CNP whereas the production of phenazine pyocyanin was strongly inhibited by CNP. The amount of 2-heptyl-4-quinolone (HHQ), a precursor to 2-heptyl-3-hydroxyl-4-quinolone (Pseudomonas quinolone signal; PQS), decreased after CNP treatment. The quantity of 2-nonyl-4-quinolone (HNQ), another quinolone which is synthesized from HHQ, was also reduced after CNP treatment. Conversely, both BNP and CNP significantly enhanced bacterial production of acylhomoserine lactone (AHL) [e.g. 3-oxo-dodecanoyl-homoserine lactone (3OC12-HSL) and butanoylhomoserine lactone (C4-HSL)]. These results correlate with an induction of lasI transcription 1 h after bacterial exposure to BNP or CNP. Concurrently, pre-treatment of P. aeruginosa PAO1 with either BNP or CNP enhanced PAO1 exotoxin A production, via a higher toxA mRNA level. At the same time, CNP led to elevated amounts of algC mRNA, indicating that algC is involved in C. elegans killing. Finally, we observed that in PAO1, Vfr protein is essential to the pro-virulent effect of CNP whereas the regulator PtxR supports only a part of the CNP pro-virulent activity. Taken together, these data reinforce the hypothesis that during

  11. IDENTIFICATION OF MAGNETITE IN B-TYPE ASTEROIDS

    SciTech Connect

    Yang Bin; Jewitt, David E-mail: jewitt@ucla.ed

    2010-09-15

    Spectrally blue (B-type) asteroids are rare, with the second discovered asteroid, Pallas, being the largest and most famous example. We conducted a focused, infrared spectroscopic survey of B-type asteroids to search for water-related features in these objects. Our results show that the negative optical spectral slope of some B-type asteroids is due to the presence of a broad absorption band centered near 1.0 {mu}m. The 1 {mu}m band can be matched in position and shape using magnetite (Fe{sub 3}O{sub 4}), which is an important indicator of past aqueous alteration in the parent body. Furthermore, our observations of B-type asteroid (335) Roberta in the 3 {mu}m region reveal an absorption feature centered at 2.9 {mu}m, which is consistent with the absorption due to phyllosilicates (another hydration product) observed in CI chondrites. The new observations suggest that at least some B-type asteroids are likely to have incorporated significant amounts of water ice and to have experienced intensive aqueous alteration.

  12. B-type Olivine Fabric induced by Grain Boundary Sliding

    NASA Astrophysics Data System (ADS)

    Précigout, Jacques; Hirth, Greg

    2013-04-01

    Olivine fabric, or Lattice Preferred Orientation (LPO), in naturally deformed peridotite largely contributes to the seismic anisotropy of the upper mantle. LPO usually results from motion of intra-crystalline dislocations during dislocation creep. In this case, experimental and numerical data indicate that the degree of mineral alignment (fabric strength) increases with increasing finite strain. Here, we show an opposite trend suggesting that olivine fabric can also result from a different deformation mechanism. Based on documentation of olivine LPOs in peridotites of a kilometer-scale mantle shear zone in the Ronda massif (Spain), we highlight a transition from a flow-parallel [a]- axis LPO (A-type fabric) to a flow-normal [a]-axis LPO (B-type fabric). While dislocation sub-structures indicate that A-type fabric results from dislocation motion, we conclude that the B-type fabric does not originate from dislocation creep, but instead from grain boundary sliding (GBS) because: (1) dislocation sub-structures remain consistent with the A-type slip system in all samples; (2) the fabric transition from A-type to B-type correlates with decreasing fabric strength despite increasing finite strain; and (3) our observations are supported by experiments that document B-type fabric in olivine aggregates where deformation involves a component of GBS. The B-type olivine fabric has a specific signature in term of seismic anisotropy, and hence, our results may have important implications for interpreting upper mantle structures and deformation processes via seismic observations.

  13. Atrial natriuretic factor and postnatal diuresis in respiratory distress syndrome.

    PubMed Central

    Rozycki, H J; Baumgart, S

    1991-01-01

    To find out if atrial natriuretic factor plays a part in the control of urine output during the initiation alone or throughout postnatal diuresis in neonates with respiratory distress syndrome, atrial natriuretic factor concentrations and clinical and renal variables were measured prospectively three times during the first three days of life in 13 premature infants. Atrial natriuretic factor concentrations rose significantly between the first and second sample times as did the urine output and output:input ratio. By the time that the third sample was taken, atrial natriuretic factor concentration had decreased significantly since the second sample had been taken, while urine flow was maintained. All subjects initiated a spontaneous diuresis that was related to the second concentration of atrial natriuretic factor. With partial correlation analysis a significant relationship was shown between the concentration of atrial natriuretic factor and the maintenance of urine output throughout the study period. Individual hormone concentrations did not, however, correlate with simultaneous renal variables. Changes in the concentrations of atrial natriuretic factor coincided with initiation of spontaneous diuresis in babies with respiratory distress syndrome, and may have a role in the complex mechanisms that maintain this diuresis. PMID:1825462

  14. Genie Pro

    Energy Science and Technology Software Center (ESTSC)

    2004-05-15

    Genie Pro is a general purpose, interactive, adaptive tool for automatically labeling regions and finding objects in large amounts of image data. Genie Pro uses supervised learning techniques to search for spatio-spectral algorithms that are best able to match exaple labels provided by a user during a training session. After Genie Pro has discovered a useful algorithm, this algorith can then be applied to other similar types of image data, to label regions and objectsmore » similar to those provided during the training session. Genie Pro was originally developed for analyzing multispectral satellite data, but it works equally well with panchromatic (grayscale) and hyperspectral satellite data, aerial imagery, and various kinds of medical imagery. AS a rough guideline, Genie Pro can work with any imagery where the scene being imaged is all approximately at a constant distance fromt he imaging device, and so the scale of imagery is fixed. Applications for Genie Pro include: Crop and terrain type mapping, Road and river network mapping, Broad area search for vehicles and buildings, and Cancer identification in histological images.« less

  15. B-type lamins in health and disease☆

    PubMed Central

    Hutchison, C.J.

    2014-01-01

    For over two decades, B-type lamins were thought to have roles in fundamental processes including correct assembly of nuclear envelopes, DNA replication, transcription and cell survival. Recent studies have questioned these roles and have instead emphasised the role of these proteins in tissue building and tissue integrity, particularly in tissues devoid of A-type lamins. Other studies have suggested that the expression of B-type lamins in somatic cells influences the rate of entry into states of cellular senescence. In humans duplication of the LMNB1 gene (encoding lamin B1) causes an adult onset neurodegenerative disorder, termed autosomal dominant leukodystrophy, whilst very recently, LMNB1 has been implicated as a susceptibility gene in neural tube defects. This is consistent with studies in mice that reveal a critical role for B-type lamins in neuronal migration and brain development. In this review, I will consider how different model systems have contributed to our understanding of the functions of B-type lamins and which of those functions are critical for human health and disease. PMID:24380701

  16. Atrial natriuretic peptide frameshift mutation in familial atrial fibrillation.

    PubMed

    Hodgson-Zingman, Denice M; Karst, Margaret L; Zingman, Leonid V; Heublein, Denise M; Darbar, Dawood; Herron, Kathleen J; Ballew, Jeffrey D; de Andrade, Mariza; Burnett, John C; Olson, Timothy M

    2008-07-10

    Atrial fibrillation is a common arrhythmia that is hereditary in a small subgroup of patients. In a family with 11 clinically affected members, we mapped an atrial fibrillation locus to chromosome 1p36-p35 and identified a heterozygous frameshift mutation in the gene encoding atrial natriuretic peptide. Circulating chimeric atrial natriuretic peptide (ANP) was detected in high concentration in subjects with the mutation, and shortened atrial action potentials were seen in an isolated heart model, creating a possible substrate for atrial fibrillation. This report implicates perturbation of the atrial natriuretic peptide-cyclic guanosine monophosphate (cGMP) pathway in cardiac electrical instability. PMID:18614783

  17. Urodilatin, a natriuretic peptide with clinical implications.

    PubMed

    Meyer, M; Richter, R; Forssmann, W G

    1998-02-21

    Natriuretic peptides (NP) constitute hormonal systems of great clinical impact. This report deals with Urodilatin (URO), a renal natriuretic peptide type A. From the gene of NP type A, a message for the preprohormone is transcribed in heart and kidney. The cardiac prohormone CDD/ANP-1-126 is synthesized in the heart atrium and processed during exocytosis forming the circulating hormone CDD/ANP-99-126. URO (CDD/ANP 95-126) is a product from the same gene, but differentially processed in the kidney and detected only in urine. Physiologically, URO acts in a paracrine fashion. After release from distal tubular kidney cells into the tubular lumen, URO binds to luminal receptors (NPR-A) in the collecting duct resulting in a cGMP-dependent signal transduction. cGMP generation is followed by an interaction with the amiloriode-sensitive sodium channel which induces diuresis and natriuresis. In this way, URO physiologically regulates fluid balance and sodium homeostasis. Moreover, URO excretion and natriuresis are in turn dependent on several physiological states, such as directly by sodium homeostasis. Pharmacologically, URO at low dose administered intravenously shows a strong diuretic and natriuretic effect and a low hypotensive effect. Renal, pulmonary, and cardiovascular effects evoked by pharmacological doses indicate that URO is a putative drug for several related diseases. Clinical trials show promising results for various clinical indications. However, the reduction in hemodialysis/hemofiltration in patients suffering from ARF following heart and liver transplantation, derived from preliminary trials recruiting a small number of patients, was not confirmed by a multicenter phase II study. In contrast, data for the prophylactic use of URO in this clinical setting suggest a better outcome for the patients. Furthermore, treatment of asthmatic patients showed a convincingly beneficial effect of URO on pulmonary function. Patients with congestive heart failure may also

  18. Clinical utility of natriuretic peptides and troponins in hypertrophic cardiomyopathy.

    PubMed

    Kehl, Devin W; Buttan, Anshu; Siegel, Robert J; Rader, Florian

    2016-09-01

    The diagnosis of hypertrophic cardiomyopathy (HCM) is based on clinical, echocardiographic and in some cases genetic findings. However, prognostication remains limited except in the subset of patients with high-risk indicators for sudden cardiac death. Additional methods are needed for risk stratification and to guide clinical management in HCM. We reviewed the available data regarding natriuretic peptides and troponins in HCM. Plasma levels of natriuretic peptides, and to a lesser extent serum levels of troponins, correlate with established disease markers, including left ventricular thickness, symptom status, and left ventricular hemodynamics by Doppler measurements. As a reflection of left ventricular filling pressure, natriuretic peptides may provide an objective measure of the efficacy of a specific therapy. Both natriuretic peptides and troponins predict clinical risk in HCM independently of established risk factors, and their prognostic power is additive. Routine measurement of biomarker levels therefore may be useful in the clinical evaluation and management of patients with HCM. PMID:27236124

  19. Atrial Natriuretic Peptide Inhibits Spontaneous Contractile Activity of Lymph Nodes.

    PubMed

    Lobov, G I; Pan'kova, M N

    2016-06-01

    Atrial natriuretic peptide dose-dependently inhibited spontaneous phase and tonic activity of smooth muscle strips from the capsule of isolated bovine mesenteric lymph nodes. Pretreatment with L-NAME, diclofenac, and methylene blue had practically no effect on the peptide-induced relaxation responses. In contrast, glibenclamide significantly reduced the inhibitory effect of atrial natriuretic peptide. We suppose that the NO-dependent and cyclooxygenase signaling pathways are not involved in implementation of the inhibitory effects of atrial natriuretic peptide. ATP-sensitive K(+)-channels of the smooth muscle cell membrane are the last component in the signaling pathway leading to relaxation of smooth muscles of the lymph node capsule caused by atrial natriuretic peptide; activation of these channels leads to membrane hyperpolarization and smooth muscle relaxation. PMID:27383173

  20. Biochemical mechanisms of atrial natriuretic factor action.

    PubMed

    Tremblay, J; Hamet, P

    1989-09-01

    Since atrial natriuretic factor (ANF) is a natriuretic and vasodilatory hormone, its mechanisms of action expectedly involve so-called negative pathways of cell stimulation, notably cyclic nucleotides. Indeed, the guanylate cyclase-cyclic GMP (cGMP) system appears to be the principal mediator of ANF's action. Specifically, particulate guanylate cyclase, a membrane glycoprotein, transmits ANF's effects, as opposed to the activation of soluble guanylate cyclase such agents as sodium nitroprusside. The stimulation of particulate guanylate cyclase by ANF manifests several characteristics. One of them is the functional irreversibility of stimulation with its apparent physiological consequences: the extended impact of ANF on diuresis and vasodilation in vivo lasts beyond the duration of increased plasma ANF levels and is accompanied by a prolonged elevation of cGMP. Another characteristic is the parallelism between guanylate cyclase stimulation and increases of cGMP in extracellular fluids. cGMP egression appears to be an active process, yet its physiological implications remain to be uncovered. In heart failure, cGMP continues to reflect augmented ANF levels, suggesting that in this disease, the lack of an ANF effect on sodium excretion is due to a defect distal to cGMP generation. In hypertension, where ANF levels are either normal or slightly elevated, probably secondary to high blood pressure, the ANF responsiveness of the particulate guanylate cyclase-cGMP system, the hypotensive effects, diuresis and natriuresis are exaggerated. The implications of this exaggerated responsiveness of the ANF-cGMP system in the pathophysiology of hypertension and its potential therapeutic connotations remain to be evaluated. PMID:2574629

  1. B-type olivine fabric induced by grain boundary sliding

    NASA Astrophysics Data System (ADS)

    Précigout, Jacques; Hirth, Greg

    2014-06-01

    Mineral Lattice Preferred Orientation (LPO) in naturally deformed peridotite is typically interpreted to result from the motion of intra-crystalline dislocations during dislocation creep. The degree of mineral alignment (fabric strength) is often assumed to increase with increasing finite strain. Here, we document olivine LPOs in peridotites in a kilometer-scale mantle shear zone in the Ronda massif (Spain) that demonstrate a transition from a flow-parallel [100]-axis LPO (A-type fabric) to a flow-normal [100]-axis LPO (B-type fabric). We conclude that the B-type fabric in the Ronda peridotite results from the enhancement of grain boundary sliding (GBS) with decreasing grain size, rather than a change in the dominant dislocation slip system because: (1) dislocation sub-structures remain consistent with the A-type slip system in all samples; (2) the fabric transition correlates with decreasing fabric strength despite increasing finite strain; (3) the analysis of deformation conditions in Ronda is inconsistent with the experimental conditions, including water content, inferred to promote the dominance of (010)[001] slip in laboratory samples, and (4) our observations are supported by experiments that document B-type fabric in olivine aggregates where deformation involves a component of GBS. Our results have important implications for interpreting the rheological properties of shear zones and upper mantle structures via micro-structural and seismic observations.

  2. Genetic Decreases in Atrial Natriuretic Peptide and Salt-Sensitive Hypertension

    NASA Astrophysics Data System (ADS)

    John, Simon W. M.; Krege, John H.; Oliver, Paula M.; Hagaman, John R.; Hodgin, Jeffrey B.; Pang, Stephen C.; Flynn, T. Geoffrey; Smithies, Oliver

    1995-02-01

    To determine if defects in the atrial natriuretic peptide (ANP) system can cause hypertension, mice were generated with a disruption of the proANP gene. Homozygous mutants had no circulating or atrial ANP, and their blood pressures were elevated by 8 to 23 millimeters of mercury when they were fed standard (0.5 percent sodium chloride) and intermediate (2 percent sodium chloride) salt diets. On standard salt diets, heterozygotes had normal amounts of circulating ANP and normal blood pressures. However, on high (8 percent sodium chloride) salt diets they were hypertensive, with blood pressures elevated by 27 millimeters of mercury. These results demonstrate that genetically reduced production of ANP can lead to salt-sensitive hypertension.

  3. Natriuretic peptide receptor 3 (NPR3) is regulated by microRNA-100.

    PubMed

    Wong, Lee Lee; Wee, Abby S Y; Lim, Jia Yuen; Ng, Jessica Y X; Chong, Jenny P C; Liew, Oi Wah; Lilyanna, Shera; Martinez, Eliana C; Ackers-Johnson, Matthew Andrew; Vardy, Leah A; Armugam, Arunmozhiarasi; Jeyaseelan, Kandiah; Ng, Tze P; Lam, Carolyn S P; Foo, Roger S Y; Richards, Arthur Mark; Chen, Yei-Tsung

    2015-05-01

    Natriuretic peptide receptor 3 (NPR3) is the clearance receptor for the cardiac natriuretic peptides (NPs). By modulating the level of NPs, NPR3 plays an important role in cardiovascular homeostasis. Although the physiological functions of NPR3 have been explored, little is known about its regulation in health or disease. MicroRNAs play an essential role in the post-transcriptional expression of many genes. Our aim was to investigate potential microRNA-based regulation of NPR3 in multiple models. Hypoxic challenge elevated levels of NPPB and ADM mRNA, as well as NT-proBNP and MR-proADM in human left ventricle derived cardiac cells (HCMa), and in the corresponding conditioned medium, as revealed by qRT-PCR and ELISA. NPR3 was decreased while NPR1 was increased by hypoxia at mRNA and protein levels in HCMa. Down-regulation of NPR3 mRNA was also observed in infarct and peri-infarct cardiac tissue from rats undergoing myocardial infarction. From microRNA microarray analyses and microRNA target predictive databases, miR-100 was selected as a candidate regulator of NPR3 expression. Further analyses confirmed up-regulation of miR-100 in hypoxic cells and associated conditioned media. Antagomir-based silencing of miR-100 enhanced NPR3 expression in HCMa. Furthermore, miR-100 levels were markedly up-regulated in rat hearts and in peripheral blood after myocardial infarction and in the blood from heart failure patients. Results from this study point to a role for miR-100 in the regulation of NPR3 expression, and suggest a possible therapeutic target for modulation of NP bioactivity in heart disease. PMID:25736855

  4. The natriuretic peptide/guanylyl cyclase--a system functions as a stress-responsive regulator of angiogenesis in mice.

    PubMed

    Kuhn, Michaela; Völker, Katharina; Schwarz, Kristine; Carbajo-Lozoya, Javier; Flögel, Ulrich; Jacoby, Christoph; Stypmann, Jörg; van Eickels, Martin; Gambaryan, Stepan; Hartmann, Michael; Werner, Matthias; Wieland, Thomas; Schrader, Jürgen; Baba, Hideo A

    2009-07-01

    Cardiac atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) modulate blood pressure and volume by activation of the receptor guanylyl cyclase-A (GC-A) and subsequent intracellular cGMP formation. Here we report what we believe to be a novel function of these peptides as paracrine regulators of vascular regeneration. In mice with systemic deletion of the GC-A gene, vascular regeneration in response to critical hind limb ischemia was severely impaired. Similar attenuation of ischemic angiogenesis was observed in mice with conditional, endothelial cell-restricted GC-A deletion (here termed EC GC-A KO mice). In contrast, smooth muscle cell-restricted GC-A ablation did not affect ischemic neovascularization. Immunohistochemistry and RT-PCR revealed BNP expression in activated satellite cells within the ischemic muscle, suggesting that local BNP elicits protective endothelial effects. Since within the heart, BNP is mainly induced in cardiomyocytes by mechanical load, we investigated whether the natriuretic peptide/GC-A system also regulates angiogenesis accompanying load-induced cardiac hypertrophy. EC GC-A KO hearts showed diminished angiogenesis, mild fibrosis, and diastolic dysfunction. In vitro BNP/GC-A stimulated proliferation and migration of cultured microvascular endothelia by activating cGMP-dependent protein kinase I and phosphorylating vasodilator-stimulated phosphoprotein and p38 MAPK. We therefore conclude that BNP, produced by activated satellite cells within ischemic skeletal muscle or by cardiomyocytes in response to pressure load, regulates the regeneration of neighboring endothelia via GC-A. This paracrine communication might be critically involved in coordinating muscle regeneration/hypertrophy and angiogenesis. PMID:19487812

  5. Changes in liraglutide-induced body composition are related to modifications in plasma cardiac natriuretic peptides levels in obese type 2 diabetic patients

    PubMed Central

    2014-01-01

    Background and aims Liraglutide treatment can improve glycemic control with a concomitant weight loss, but the underlying mechanism on weight loss is not completely understood. Cardiac natriuretic peptides (NPs) can resist body fat accumulation through increasing adipocytes lypolysis. In this study, we tested the hypothesis that liraglutide-induced weight loss was associated with increased plasma NPs concentrations. Methods Thirty-one outpatients with type 2 diabetes (T2D) treated with metformin and other oral antidiabetic drugs except for thiazolidinediones (TZDs) were subcutaneously administered with liraglutide for 12 weeks. Body composition, abdominal visceral adipose tissue areas (VAT) and subcutaneous adipose tissue areas (SAT) were assessed at pre- and post-treatment by dual-energy X-ray absorptiometry (DXA) scanning and abdominal computerized tomography (CT). Plasma atrial natriuretic peptides (ANP) and B-type ventricular natriuretic peptides (BNP) concentrations were tested by commercial ELISA Kit quantitatively. Results Following 12-week liraglutide treatment, body weight, waist circumference, total fat and lean mass, fat percentage, SAT and VAT areas were significantly reduced from baseline. Concurrently, plasma ANP and BNP levels were significantly increased following 12-week liraglutide treatment. There were significant correlations between the reductions in body compositions and the increases in both plasma ANP and BNP levels. Conclusions There were significant correlations between increases in both plasma ANP and BNP levels and changes in liraglutide-induced body composition. Our data implied that increases in plasma NPs may add a novel dimension to explain how liraglutide induces weight loss. PMID:24498905

  6. Incremental predictive value of natriuretic peptides for prognosis in the chronic stable heart failure population: a systematic review.

    PubMed

    Don-Wauchope, Andrew C; Santaguida, Pasqualina L; Oremus, Mark; McKelvie, Robert; Ali, Usman; Brown, Judy A; Bustamam, Amy; Sohel, Nazmul; Hill, Stephen A; Booth, Ronald A; Balion, Cynthia; Raina, Parminder

    2014-08-01

    The aim of this study was to determine whether measurement of natriuretic peptides independently adds incremental predictive value for mortality and morbidity in patients with chronic stable heart failure (CSHF). We electronically searched Medline®, Embase™, AMED, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and CINAHL from 1989 to June 2012. We also searched reference lists of included articles, systematic reviews, and the gray literature. Studies were screened for eligibility criteria and assessed for methodological quality. Data were extracted on study design, population demographics, assay cutpoints, prognostic risk prediction model covariates, statistical methods, outcomes, and results. One hundred and eighty-three studies were identified as prognostic in the systematic review. From these, 15 studies (all NT-proBNP) considered incremental predictive value in CSHF subjects. Follow-up varied from 12 to 37 months. All studies presented at least one estimate of incremental predictive value of NT-proBNP relative to the base prognostic model. Using discrimination or likelihood statistics, these studies consistently showed that NT-proBNP increased model performance. Three studies used re-classification and model validation computations to establish incremental predictive value; these studies showed less consistency with respect to added value. Although there were differences in the base risk prediction models, assay cutpoints, and lengths of follow-up, there was consistency in NT-proBNP adding incremental predictive value for prognostic models in chronic stable CSHF patients. The limitations in the literature suggest that studies designed to evaluate prognostic models should be undertaken to evaluate the incremental value of natriuretic peptide as a predictor of mortality and morbidity in CSHF. PMID:25120174

  7. Investigations of the Magnetic a and B Type Stars

    NASA Astrophysics Data System (ADS)

    Wade, Gregg Allan

    In an effort to explore further the mechanisms responsible for magnetism and chemical peculiarity in the early-type stars, I have constructed models of the magnetic fields of individual A and B type stars, studied the evolutionary dependence of magnetism in the Ap/Bp stars, undertaken the first systematic study of linear polarisation in the spectral lines of magnetic A and B type stars, and searched for magnetic fields in the photospheres of canonically non-magnetic upper-main sequence stars. I present detailed studies of 8 magnetic Ap, Bp and He-strong stars. For 7 of these objects (84 UMa, iota Cas, HD 115708, HD 184927, HD 200311, HD 81009, and HD 192678) new models of the surface magnetic field structure have been developed using longitudinal field, field modulus, and broadband linear polarisation measurements. These models represent a substantial contribution to the accumulated data regarding the surface magnetic fields of upper-main sequence stars. One object (HD 59435) is in fact a spectroscopic binary (SB2), the secondary component of which is a magnetic Ap star. A detailed study of the evolutionary state of the components and the mean magnetic field modulus variation of the secondary is presented. The results of this analysis are consistent with the suggestion by Hubrig & Mathys (1994) that magnetism (and perhaps chemical peculiarity) arise late in the evolution of A and B type stars. In order to test further this possibility, a more extensive study of the evolutionary states and magnetic fields of 10 magnetic Ap stars was undertaken. This study indicates that the magnetic stars are distributed across the entire width of the main sequence, a result inconsistent with the hypothesis of Hubrig & Mathys. I furthermore present investigations of the Zeeman circular and linear polarisation measured within stellar spectral lines. The MuSiCoS spectropolarimeter was used to conduct the first systematic, high signal-to-noise ratio observations of Zeeman linear

  8. Physiology of natriuretic peptides: The volume overload hypothesis revisited

    PubMed Central

    Arjamaa, Olli

    2014-01-01

    The discovery of the natriuretic peptide system in the early 1980s aroused great interest among clinical cardiologists. The heart was not a mechanical pump alone, but also an endocrine organ that had powerful effects on blood circulation. Natriuretic peptides caused both natriuresis and diuresis, and they responded to a volume overload which caused either stretch or pressure on the heart. As a result, the findings led to the conclusion that the human body had a hormone with effects similar to those of a drug which treats high blood pressure. Later, it became evident that the volume contraction was fortified by extrarenal plasma shift. Here, a hypothesis is presented in which the role of natriuretic peptides is to regulate oxygen transport as the volume contraction leads to hemoconcentration with an increased oxygen-carrying capacity. Wall stress, either chemical or mechanical, changes the oxygen gradient of the myocardium and affects the diffusion of oxygen within a myocyte. In support of this hypothesis, hypoxia-response elements have been found in both the atrial natriuretic peptide and the brain natriuretic peptide genes. PMID:24527182

  9. Natriuretic peptides for the treatment of acute heart failure: a focus on nesiritide in recent clinical trials.

    PubMed

    Fajardo, Jeff; Heywood, J Thomas; Patterson, J Herbert; Adams, Kirkwood; Chow, Sheryl L

    2015-01-01

    Nesiritide, a recombinant form of B-type natriuretic peptide, is a vasodilator and currently recommended as an additive therapy for patients with acute decompensated heart failure (ADHF) who have been optimized on loop diuretics. With hospitalizations for ADHF rising, appropriate selection of therapy becomes even more important to optimize efficacy and reduce adverse events. Nesiritide has many properties that antagonize the pathophysiologic processes of heart failure and has demonstrated a comparative benefit in previous reports; however, controversy still remains with respect to its efficacy and safety. Based on results from recent clinical trials, nesiritide has been shown to be safe at currently approved doses and strongly considered for the treatment of ADHF in patients who remain symptomatic despite optimal doses of intravenous loop divertics. PMID:26028173

  10. Atrial natriuretic factor increases vascular permeability

    NASA Technical Reports Server (NTRS)

    Lockette, Warren; Brennaman, Bruce

    1990-01-01

    An increase in central blood volume in microgravity may result in increased plasma levels of atrial natriuretic factor (ANF). In this study, it was determined whether ANF increases capillary permeability to plasma protein. Conscious, bilaterally nephrectomized male rats were infused with either saline, ANF + saline, or hexamethonium + saline over 2 h following bolus injections of (I-125)-albumin and (C-14)-dextran of similar molecular size. Blood pressure was monitored, and serial determinations of hematocrits were made. Animals infused with 1.0 microg/kg per min ANF had significantly higher hematocrits than animals infused with saline vehicle. Infusion of ANF increased the extravasation of (I-125)-albumin, but not (C-14)-dextran from the intravascular compartment. ANF also induced a depressor response in rats, but the change in blood pressure did not account for changes in capillary permeability to albumin; similar depressor responses induced by hexamethonium were not accompanied by increased extravasation of albumin from the intravascular compartment. ANF may decrease plasma volume by increasing permeability to albumin, and this effect of ANF may account for some of the signs and symptoms of space motion sickness.

  11. Atrial natriuretic factor increases vascular permeability

    SciTech Connect

    Lockette, W.; Brennaman, B. )

    1990-12-01

    An increase in central blood volume in microgravity may result in increased plasma levels of atrial natriuretic factor (ANF). Since elevations in plasma ANF are found in clinical syndromes associated with edema, and since space motion sickness induced by microgravity is associated with an increase in central blood volume and facial edema, we determined whether ANF increases capillary permeability to plasma protein. Conscious, bilaterally nephrectomized male rats were infused with either saline, ANF + saline, or hexamethonium + saline over 2 h following bolus injections of 125I-albumin and 14C-dextran of similar molecular size. Blood pressure was monitored and serial determinations of hematocrits were made. Animals infused with 1.0 micrograms.kg-1.min-1 ANF had significantly higher hematocrits than animals infused with saline vehicle. Infusion of ANF increased the extravasation of 125I-albumin, but not 14C-dextran from the intravascular compartment. ANF also induced a depressor response in rats, but the change in blood pressure did not account for changes in capillary permeability to albumin; similar depressor responses induced by hexamethonium were not accompanied by increased extravasation of albumin from the intravascular compartment. ANF may decrease plasma volume by increasing permeability to albumin, and this effect of ANF may account for some of the signs and symptoms of space motion sickness.

  12. Boron Abundances in A and B-type Stars

    NASA Technical Reports Server (NTRS)

    Lambert, David L.

    1997-01-01

    Boron abundances in A- and B-type stars may be a successful way to track evolutionary effects in these hot stars. The light elements - Li, Be, and B - are tracers of exposure to temperatures more moderate than those in which the H-burning CN-cycle operates. Thus, any exposure of surface stellar layers to deeper layers will affect these light element abundances. Li and Be are used in this role in investigations of evolutionary processes in cool stars, but are not observable in hotter stars. An investigation of boron, however, is possible through the B II 1362 A resonance line. We have gathered high resolution spectra from the IUE database of A- and B-type stars near 10 solar mass for which nitrogen abundances have been determined. The B II 1362 A line is blended throughout; the temperature range of this program, requiring spectrum syntheses to recover the boron abundances. For no star could we synthesize the 1362 A region using the meteoritic/solar boron abundance of log e (B) = 2.88; a lower boron abundance was necessary which may reflect evolutionary effects (e.g., mass loss or mixing near the main-sequence), the natal composition of the star forming regions, or a systematic error in the analyses (e.g., non-LTE effects). Regardless of the initial boron abundance, and despite the possibility of non-LTE effects, it seems clear that boron is severely depleted in some stars. It may be that the nitrogen and boron abundances are anticorrelated, as would be expected from mixing between the H-burning and outer stellar layers. If, as we suspect, a residue of boron is present in the A-type supergiants, we may exclude a scenario in which mixing occurs continuously between the surface and the deep layers operating the CN-cycle. Further exploitation of the B II 1362 A line as an indicator of the evolutionary status of A- and B-type stars will require a larger stellar sample to be observed with higher signal-to-noise as attainable with the Hubble Space Telescope.

  13. Lebetin 2, a Snake Venom-Derived Natriuretic Peptide, Attenuates Acute Myocardial Ischemic Injury through the Modulation of Mitochondrial Permeability Transition Pore at the Time of Reperfusion.

    PubMed

    Tourki, Bochra; Matéo, Philippe; Morand, Jessica; Elayeb, Mohamed; Godin-Ribuot, Diane; Marrakchi, Naziha; Belaidi, Elise; Messadi, Erij

    2016-01-01

    Cardiac ischemia is one of the leading causes of death worldwide. It is now well established that natriuretic peptides can attenuate the development of irreversible ischemic injury during myocardial infarction. Lebetin 2 (L2) is a new discovered peptide isolated from Macrovipera lebetina venom with structural similarity to B-type natriuretic peptide (BNP). Our objectives were to define the acute cardioprotective actions of L2 in isolated Langendorff-perfused rat hearts after regional or global ischemia-reperfusion (IR). We studied infarct size, left ventricular contractile recovery, survival protein kinases and mitochondrial permeability transition pore (mPTP) opening in injured myocardium. L2 dosage was determined by preliminary experiments at its ability to induce cyclic guanosine monophosphate (cGMP) release without changing hemodynamic effects in normoxic hearts. L2 was found to be as effective as BNP in reducing infarct size after the induction of either regional or global IR. Both peptides equally improved contractile recovery after regional IR, but only L2 increased coronary flow and reduced severe contractile dysfunction after global ischemia. Cardioprotection afforded by L2 was abolished after isatin or 5-hydroxydecanote pretreatment suggesting the involvement of natriuretic peptide receptors and mitochondrial KATP (mitoKATP) channels in the L2-induced effects. L2 also increased survival protein expression in the reperfused myocardium as evidenced by phosphorylation of signaling pathways PKCε/ERK/GSK3β and PI3K/Akt/eNOS. IR induced mitochondrial pore opening, but this effect was markedly prevented by L2 treatment. These data show that L2 has strong cardioprotective effect in acute ischemia through stimulation of natriuretic peptide receptors. These beneficial effects are mediated, at least in part, by mitoKATP channel opening and downstream activated survival kinases, thus delaying mPTP opening and improving IR-induced mitochondrial dysfunction. PMID

  14. b-Type Cytochromes in Higher Plant Plasma Membranes 1

    PubMed Central

    Asard, Han; Venken, Mireille; Caubergs, Roland; Reijnders, Willem; Oltmann, Fred L.; De Greef, Jan A.

    1989-01-01

    The composition and characteristics of b-type cytochromes from higher plant plasma membranes, purified using aqueous two-phase partitioning, were investigated. At least three different cytochromes were identified by their wavelength maxima and redox midpoint potentials (E0′). Cytochrome b-560.7 (E0′ from + 110 to + 160 millivolts) was present in zucchini (Cucurbita pepo) hypocotyls and bean (Phaseolus vulgaris L.) hooks, although in different concentrations. The main component in cauliflower (Brassica oleracea L.) inflorescences (cytochrome b-558.8) is probably functionally similar to this cytochrome. The plasma membrane generally contains two to three cytochrome species. However, the occurrence and concentrations were species dependent. The high potential cytochrome can be reduced by ascorbate but not NADH, and may be involved in blue light perception. PMID:16666854

  15. The potential value of integrated natriuretic peptide and echo-guided heart failure management.

    PubMed

    Scali, Maria Chiara; Simioniuc, Anca; Dini, Frank Lloyd; Marzilli, Mario

    2014-01-01

    There is increasing interest in guiding Heart Failure (HF) therapy with Brain Natriuretic Peptide (BNP) or N-terminal prohormone of Brain Natriuretic Peptide (NT-proBNP), with the goal of lowering concentrations of these markers (and maintaining their suppression) as part of the therapeutic approach in HF. However, recent European Society of Cardiology (ESC) and American Heart Association/ American College of Cardiology (AHA/ACC) guidelines did not recommend biomarker-guided therapy in the management of HF patients. This has likely to do with the conceptual, methodological, and practical limitations of the Natriuretic Peptides (NP)-based approach, including biological variability, slow time-course, poor specificity, cost and venipuncture, as well as to the lack of conclusive scientific evidence after 15 years of intensive scientific work and industry investment in the field. An increase in NP can be associated with accumulation of extra-vascular lung water, which is a sign of impending acute heart failure. If this is the case, an higher dose of loop diuretics will improve symptoms. However, if no lung congestion is present, diuretics will show no benefit and even harm. It is only a combined clinical, bio-humoral (for instance with evaluation of renal function) and echocardiographic assessment which may unmask the pathophysiological (and possibly therapeutic) heterogeneity underlying the same clinical and NP picture. Increase in B-lines will trigger increase of loop diuretics (or dialysis); the marked increase in mitral insufficiency (at baseline or during exercise) will lead to increase in vasodilators and to consider mitral valve repair; the presence of substantial inotropic reserve during stress will give a substantially higher chance of benefit to beta-blocker or Cardiac Resynchronization Therapy (CRT). To each patient its own therapy, not with a "blind date" with symptoms and NP and carpet bombing with drugs, but with an open-eye targeted approach on the

  16. Carbides with Filled Re 3B-Type Structure

    NASA Astrophysics Data System (ADS)

    Witte, Anne M.; Jeitschko, Wolfgang

    1994-10-01

    The new compounds AFe2SiC (A = Y, Sm, Gd, Tb, Ho, Er, Tm, Lu, Th, U) were prepared by arc-melting cold-pressed pellets of the elemental components. They are isotypic with the orthorhombic DyFe2SiC-type structure, which was refined from single-crystal X-ray data of ThFe2SiC: Cmcm, a = 386.32(6) pm, b = 1080.6(1) pm, c = 695.0(1) pm, Z = 4, R = 0.020 for 559 structure factors and 17 variable parameters. The polyanionic iron-silicon-carbon network is three-dimensionally infinite. The carbon atoms are situated in octahedral voids formed by four thorium and two iron atoms. The hydrolysis of ErFe2SiC with diluted hydrochloric acid yields mainly methane besides C2 and C3 hydro-carbons. A large number of compounds can be classified to crystallize with a filled-up version of the Re3B-type structure. They are isotypic with V3AsC, where the positions of the vanadium and arsenic atoms correspond to the atomic positions of Re3B and the carbon atoms fill octahedral voids formed by the vanadium atoms. The DyFe2SiC-type structure also can be described as a filled-up Re3B structure; however, the carbon atoms of DyFe2SiC occupy different octahedral voids.

  17. Fundamental properties of nearby single early B-type stars

    NASA Astrophysics Data System (ADS)

    Nieva, María-Fernanda; Przybilla, Norbert

    2014-06-01

    Aims: Fundamental parameters of a sample of 26 apparently slowly-rotating single early B-type stars in OB associations and in the field within a distance of ≲400 pc from the Sun are presented and compared to high-precision data from detached eclipsing binaries (DEBs). Together with surface abundances for light elements the data are used to discuss the evolutionary status of the stars in context of the most recent Geneva grid of models for core hydrogen-burning stars in the mass-range ~6 to 18 M⊙ at metallicity Z = 0.014. Methods: The fundamental parameters are derived on the basis of accurate and precise atmospheric parameters determined earlier by us from non-LTE analyses of high-quality spectra of the sample stars, utilising the new Geneva stellar evolution models. Results: Evolutionary masses plus radii and luminosities are determined to better than typically 5%, 10%, and 20% uncertainty, respectively, facilitating the mass-radius and mass-luminosity relationships to be recovered for single core hydrogen-burning objects with a similar precision as derived from DEBs. Good agreement between evolutionary and spectroscopic masses is found. Absolute visual and bolometric magnitudes are derived to typically ~0.15-0.20 mag uncertainty. Metallicities are constrained to better than 15-20% uncertainty and tight constraints on evolutionary ages of the stars are provided. Overall, the spectroscopic distances and ages of individual sample stars agree with independently derived values for the host OB associations. Signatures of mixing with CN-cycled material are found in 1/3 of the sample stars. Typically, these are consistent with the amount predicted by the new Geneva models with rotation. The presence of magnetic fields appears to augment the mixing efficiency. In addition, a few objects are possibly the product of binary evolution. In particular, the unusual characteristics of τ Sco point to a blue straggler nature, due to a binary merger. Conclusions: The accuracy

  18. Serum Levels of Cardiac Markers NT-proANP and NT-proBNP in Brachycephalic bitches at Different Gestational Stages.

    PubMed

    Feliciano, Mar; Uscategui, R R; Maciel, G S; de Almeida, V T; Silveira, M F; de Oliveira, Gac; Vicente, Wrr

    2016-06-01

    The aim of this study was to determine serum levels of natriuretic peptide precursors (NT-proANP and NT-proBNP) during pregnancy in brachycephalic bitches. Fifteen healthy multiparous bitches were selected for this prospective study. Serum levels of NT-proANP and NT-proBNP were measured during anoestrous and at 14, 35, 42, 49 and 56 days (2nd, 5th, 6th, 7th and 8th weeks) of pregnancy. Fourteen animals had normal gestations, and one bitch developed single foetus syndrome. The natriuretic peptide levels of this animal were not included in this study; however, it is important to report that its NT-proANP levels were four times greater than those of normal patients. There was no significant difference (p = 0.072) in NT-proBNP levels between anoestrous (0.20 ± 0.10 ng/ml) and the different pregnancy weeks (0.27 ± 0.12 ng/ml). There was a positive correlation (p < 0.0001) between NT-proANP and gestational age, and the levels of this marker increased significantly (p < 0.0001) during the 6th (0.26 ± 0.06 ng/ml), 7th (0.28 ± 0.04 ng/ml) and 8th weeks (0.29 ± 0.05 ng/ml) when compared to anoestrous (0.18 ± 0.02 ng/ml). NT-proANP serum levels are correlated with gestational development and may be indicative of cardiovascular adaptation in canine brachycephalic pregnancy. PMID:26991598

  19. Natriuretic peptides in the regulation of the hypothalamic-pituitary-adrenal axis.

    PubMed

    Porzionato, Andrea; Macchi, Veronica; Rucinski, Marcin; Malendowicz, Ludwik K; De Caro, Raffaele

    2010-01-01

    Atrial (ANP), brain (BNP), and C-type (CNP) natriuretic peptides act by binding to three main subtypes of receptors, named NPR-A, -B, and -C. NPR-A and NPR-B are coupled with guanylate cyclase. Not only NPR-C is involved in removing natriuretic peptides from the circulation but it also acts through inhibition of adenylyl cyclase. NPR-A binds ANP and BNP; NPR-B preferentially binds CNP; and NPR-C binds all natriuretic peptides with similar affinities. All natriuretic peptides and their receptors are widely present in the hypothalamus, pituitary, adrenal cortex, and medulla. In the hypothalamus, they reduce norepinephrine release, inhibit oxytocin, vasopressin, corticotropin-releasing factor, and luteinizing hormone-releasing hormone release. In the hypophysis, natriuretic peptides inhibit basal and induced ACTH release. Conversely, the effects of natriuretic peptides on secretion of growth, luteinizing, and follicle-stimulating hormones are not clear. Natriuretic peptides are known to inhibit basal and stimulated aldosterone secretion, through an increase of intracellular cGMP, and to inhibit the growth of zona glomerulosa. Inhibition or stimulation of glucocorticoid secretion by adrenocortical cells has been reported on the basis of the species involved, and an indirect effect mediated by adrenalmedullary cells has been hypothesized. In the adrenal medulla, natriuretic peptides inhibit catecholamine release and increase catecholamine uptake. It appears that natriuretic peptides may play a role in the pathophysiology of adrenocortical neoplasias and pheochromocytomas. PMID:20797680

  20. Exaggerated NT-proBNP production in patients with hematologic malignancies: a case series.

    PubMed

    Andreu, Aileen; Guglin, Maya

    2012-01-01

    ©2011 Wiley Periodicals Inc. Extremely elevated serum brain natriuretic peptide (BNP) in cancer patients is a poorly understood phenomenon. The authors report three cases of patients with hematologic malignancies and serial N-terminal pro-BNP (NT-proBNP) measurements with values in the range of tens to hundred thousands pg/mL. Through matching NT-proBNP results with clinical, laboratory, echocardiographic and radiologic data, the authors found that these patients demonstrated exaggerated responses to fluid overload. Patients with hematologic malignancies may have higher than expected values of NT-proBNP in response to hypervolemic states. The authors hypothesize that this may be related to possible infiltration of the myocardium by substances produced in the setting of these diseases or due to proteins interfering with the assay.Congest Heart Fail. PMID:23167814

  1. The propeptide Asn1-Tyr126 is the storage form of rat atrial natriuretic factor.

    PubMed Central

    Thibault, G; Garcia, R; Gutkowska, J; Bilodeau, J; Lazure, C; Seidah, N G; Chrétien, M; Genest, J; Cantin, M

    1987-01-01

    Granules from rat atria were isolated by differential centrifugation and by a 53% (v/v) Percoll gradient after tissue homogenization in 0.25 M-sucrose/50 mM-Na2EDTA. About 40% of the immunoreactive ANF (atrial natriuretic factor) sedimented with the atrial granules during differential centrifugations. On the Percoll gradient, two distinct bands were observed. Cell debris, mitochondria, lysosomes, myofilaments and microsomes were mostly contained in the lightest-density (rho) (1.03-1.07 g/ml) fraction, as demonstrated by electron microscopy and by enzymic markers such as lactate dehydrogenase, monoamine oxidase, cytochrome c reductase, beta-glucuronidase and acid phosphatase. Atrial granules were mostly contained in the denser (rho 1.11-1.15 g/ml) band and were only slightly contaminated by lysosomes, as shown by beta-glucuronidase activity. Analysis of the ANF content in these isolated granules by h.p.l.c., amino acid composition and sequencing demonstrated that it was only the pro-ANF [ANF-(Asn1-Tyr126)-peptide]. The precursor was present in all granules, as demonstrated by immunocytochemistry. Since hormonal propeptides usually undergo intracellular processing, and the matured peptides are subsequently stored in the secretory granules, these results indicate that the processing pathway of ANF may be different from that of other hormonal peptides. Images Fig. 2. Fig. 5. PMID:2952112

  2. Anhedonia and altered cardiac atrial natriuretic peptide following chronic stressor and endotoxin treatment in mice.

    PubMed

    Wann, Boubacar Pasto; Audet, Marie-Claude; Gibb, Julie; Anisman, Hymie

    2010-02-01

    Chronic stressors and inflammatory immune activation may contribute to pathophysiological alterations associated with both major depression and cardiovascular disease. The present study, conducted in mice, assessed whether a chronic stressor of moderate severity that induced an anhedonic effect, when coupled with a bacterial endotoxin, lipopolysaccharide (LPS), additively or interactively provoked circulating and heart atrial natriuretic peptide (ANP), a potentially useful diagnostic and prognostic tool in cardiac diseases. As well, given the potential role of inflammatory processes in both depression and cardiovascular disease, we assessed pro-inflammatory mRNA expression in heart in response to the stressor and the LPS treatments. Male CD-1 mice that had been exposed to a chronic, variable stressor over 4 weeks displayed reduced sucrose consumption, possibly reflecting the anhedonic effects of the stressor. Treatment with LPS (10mug) provoked increased circulating corticosterone levels in both chronically stressed and non-stressed mice. Moreover, ANP concentrations in plasma and in the left ventricle were increased by both the stressor and the LPS treatments, as were left atrial and ventricular cytokine (interleukin-1beta; tumor necrosis factor-alpha) mRNA expression. Further, these treatments synergistically influenced the rise of plasma ANP. A link may exist between stressor-provoked depressive features (anhedonia) and immune activation, with elevated levels of ANP, a potential marker of cardiovascular disturbance. These findings are consistent with the view that chronic stressors and inflammatory immune activation may represent a common denominator subserving the frequent comorbidity between these illnesses. PMID:19604644

  3. Mechanical ventilation with positive end-expiratory pressure decreases the circulating concentrations of the N-terminus and C-terminus of the atrial natriuretic factor prohormone.

    PubMed

    Vesely, D L; Salmon, J S

    1990-01-01

    Mechanical ventilation with positive end-expiratory pressure (PEEP) decreases urine output and urinary sodium excretion. The influence of PEEP during controlled mechanical ventilation on the circulating concentrations of the N-terminus and C-terminus of the atrial natriuretic factor (ANF) prohormone which both contain natriuretic and diuretic peptides was investigated in 7 patients with acute respiratory failure. The 98 amino acid (aa) N-terminus, the midportion of the N-terminus consisting of aa 31-67 of the 126 aa ANF prohormone (i.e., pro ANF 31-67) and the C-terminus (aa 99-126; ANF) were found to be significantly (p less than 0.05; ANOVA) elevated compared to 54 healthy volunteers during acute respiratory failure prior to institution of PEEP. With institution of 10 cm of H2O of PEEP all 7 patients had a significant (p less than 0.05) decrease in the circulating concentrations of pro ANFs 1-98, 31-67 and ANF. These findings suggest that the increased thoracic pressure secondary to PEEP which reduces venous return and lowers atrial filling pressure results in a decreased release of the N-terminus and C-terminus of the ANF prohormone. This decrease in the N-terminus and C-terminus of the ANF prohormone appears to represent a physiologic mechanism for restoration of intravascular volume, secondary to decreased sodium excretion. PMID:2151585

  4. Associations of plasma natriuretic peptide, adrenomedullin, and homocysteine levels with alterations in arterial stiffness: The Framingham Heart Study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Experimental studies suggest that the natriuretic peptides influence lipid and fatty acid metabolism. Although it has been shown that obese individuals have reduced natriuretic peptide levels, conflicting data exist on the relation of natriuretic peptide levels to other metabolic risk factors. We ex...

  5. Atrial Natriuretic Peptide and Renal Dopaminergic System: A Positive Friendly Relationship?

    PubMed Central

    Choi, Marcelo Roberto; Rukavina Mikusic, Natalia Lucía; Kouyoumdzian, Nicolás Martín; Kravetz, María Cecilia; Fernández, Belisario Enrique

    2014-01-01

    Sodium metabolism by the kidney is accomplished by an intricate interaction between signals from extrarenal and intrarenal sources and between antinatriuretic and natriuretic factors. Renal dopamine plays a central role in this interactive network. The natriuretic hormones, such as the atrial natriuretic peptide, mediate some of their effects by affecting the renal dopaminergic system. Renal dopaminergic tonus can be modulated at different steps of dopamine metabolism (synthesis, uptake, release, catabolism, and receptor sensitization) which can be regulated by the atrial natriuretic peptide. At tubular level, dopamine and atrial natriuretic peptide act together in a concerted manner to promote sodium excretion, especially through the overinhibition of Na+, K+-ATPase activity. In this way, different pathological scenarios where renal sodium excretion is dysregulated, as in nephrotic syndrome or hypertension, are associated with impaired action of renal dopamine and/or atrial natriuretic peptide, or as a result of impaired interaction between these two natriuretic systems. The aim of this review is to update and comment on the most recent evidences demonstrating how the renal dopaminergic system interacts with atrial natriuretic peptide to control renal physiology and blood pressure through different regulatory pathways. PMID:25013796

  6. A Test in Context Critical Evaluation of Natriuretic Peptide Testing in Heart Failure

    PubMed Central

    Francis, Gary S.; Felker, G. Michael; Tang, W.H. Wilson

    2016-01-01

    Circulating natriuretic peptide measurements have been used extensively over the past 15 years to diagnose and monitor patients with heart failure. We are still learning how complex the dynamics of natriuretic peptides can be in the interpretation of test results in individual patients. Although natriuretic peptide measurements are widely used in practice, there are questions regarding why these peptides may not necessarily track with blood volume or invasive hemodynamic measurements in individual patients. Interpretation of natriuretic peptide measurements will depend on many factors, including special patient populations, obesity, renal function, the state of congestion or decongestion, and whether patients are receiving specific therapies. Natriuretic peptide measurements have clearly revolutionized clinical care for patients with heart failure, but further research should provide insights to help use these measurements to individualize patient care beyond the current guidelines. PMID:26796399

  7. C-TYPE NATRIURETIC PEPTIDE (CNP): CARDIOVASCULAR ROLES AND POTENTIAL AS A THERAPEUTIC TARGET

    PubMed Central

    Lumsden, Natalie G.; Khambata, Rayomand S.; Hobbs, Adrian J.

    2012-01-01

    Natriuretic peptides play a fundamental role in cardiovascular homeostasis by modulation of fluid and electrolyte balance and vascular tone. C-type natriuretic peptide (CNP) represents the paracrine element of the natriuretic peptide axis which complements the endocrine actions of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). CNP is produced by the endothelium and the heart and appears to play a prominent role in vascular and cardiac function, both physiologically and pathologically. This provides a rationale for the therapeutic potential of pharmacological interventions targeted to CNP signalling. This article provides an overview of the biology and pharmacology of CNP, with emphasis on the cardiovascular system, and discusses pathologies in which drugs designed to manipulate CNP signalling maybe of clinical benefit. PMID:21247399

  8. A Test in Context: Critical Evaluation of Natriuretic Peptide Testing in Heart Failure.

    PubMed

    Francis, Gary S; Felker, G Michael; Tang, W H Wilson

    2016-01-26

    Circulating natriuretic peptide measurements have been used extensively over the past 15 years to diagnose and monitor patients with heart failure. We are still learning how complex the dynamics of natriuretic peptides can be in the interpretation of test results in individual patients. Although natriuretic peptide measurements are widely used in practice, there are questions regarding why these peptides may not necessarily track with blood volume or invasive hemodynamic measurements in individual patients. Interpretation of natriuretic peptide measurements will depend on many factors, including special patient populations, obesity, renal function, the state of congestion or decongestion, and whether patients are receiving specific therapies. Natriuretic peptide measurements have clearly revolutionized clinical care for patients with heart failure, but further research should provide insights to help use these measurements to individualize patient care beyond the current guidelines. PMID:26796399

  9. Preparation, structure, and digestibility of crystalline A- and B-type aggregates from debranched waxy starches.

    PubMed

    Cai, Liming; Shi, Yong-Cheng

    2014-05-25

    Highly crystalline A- and B-type aggregates were prepared from short linear α-1,4 glucans generated from completely debranched waxy maize and waxy potato starches by manipulating the chain length and crystallization conditions including starch solids concentration and crystallization temperature. The A-type crystalline products were more resistant to enzyme digestion than the B-type crystalline products, and the digestibility of the A- and B-type allomorphs was not correlated with the size of the aggregates formed. Annealing increased the peak melting temperature of the B-type crystallites, making it similar to that of the A-type crystallites, but did not improve the enzyme resistance of the B-type crystalline products. The possible reason for these results was due to the compact morphology as well as the denser packing pattern of double helices in A-type crystallites. Our observations counter the fact that most B-type native starches are more enzyme-resistant than A-type native starches. Crystalline type per se does not seem to be the key factor that controls the digestibility of native starch granules; the resistance of native starches with a B-type X-ray diffraction pattern is probably attributed to the other structural features in starch granules. PMID:24708989

  10. Natriuretic peptide receptor-B (guanylyl cyclase-B) mediates C-type natriuretic peptide relaxation of precontracted rat aorta.

    PubMed

    Drewett, J G; Fendly, B M; Garbers, D L; Lowe, D G

    1995-03-01

    The most potent known agonist for the natriuretic peptide receptor-B (NPR-B)/guanylyl cyclase-B is C-type natriuretic peptide (CNP). A homologous ligand-receptor system consists of atrial natriuretic peptide (ANP) and NPR-A/guanylyl cyclase-A. A third member of this family is NPR-C, a non-guanylyl cyclase receptor. Monoclonal antibodies were raised against NPR-B by immunizing mice with a purified receptor-IgG fusion protein consisting of the extracellular domain of NPR-B and the Fc portion of human IgG-gamma 1. One monoclonal antibody, 3G12, did not recognize NPR-A or NPR-C and bound to human and rat NPR-B. CNP binding to NPR-B and stimulation of cGMP synthesis were inhibited by 3G12. With cells isolated from either the media or adventitia layers of rat thoracic aorta, 3G12 did not interfere with ANP-stimulated cGMP synthesis, but it inhibited CNP-stimulated cGMP levels in cells from both layers. CNP (IC50 = 10 nM) and ANP (IC50 = 1 nM) caused relaxation of phenylephrine-contracted rat aortic rings. 3G12 caused a marked increase in the IC50 for CNP, from 10 nM to 140 nM, but failed to affect ANP-mediated relaxation. Therefore, our results for the first time demonstrate that CNP relaxes vascular smooth muscle by virtue of its binding to NPR-B. PMID:7876238

  11. N-terminal natriuretic peptide and ventilation-perfusion lung scan in sickle cell disease and thalassemia patients with pulmonary hypertension.

    PubMed

    Mokhtar, Galila M; Adly, Amira A M; El Alfy, Mohsen S; Tawfik, Lamis M; Khairy, Ahmed T

    2010-01-01

    The aim of this study was to determine the prevalence of pulmonary hypertension (PH) in sickle cell disease and thalassemia patients in relation to clinical and laboratory parameters of hemolysis and hemosidersosis, as well as plasma N-terminal pro-brain natriuretic peptide (NT-pro-BNP). The study also aimed to define the role of thromboembolic pulmonary artery (PA) obstruction in its etiology. Forty sickle cell disease and 30 thalassemia patients [15 beta-thalassemia major (beta-TM) and 15 beta-thalassemia intermedia (beta-TI)] were screened for PH defined as tricuspid regurgitant velocity (TRV) >2.5 m/sec and evaluated for PA obstruction using ventilation-perfusion lung scan (V/Q), together with measurement of their plasma levels of NT-pro-BNP. Patients were prospectively followed up for a mean of 18 +/- 6.1 months. The prevalence of PH was 37.5, 40.0 and 26.7% in sickle cell disease, beta-TI and beta-TM patients, respectively. Pulmonary hypertension patients were older, had longer disease duration, higher serum ferritin, serum lactate dehydrogenase (LDH) and NT-pro-BNP with lower hemoglobin (Hb) levels compared to patients without PH. N-terminal pro-BNP was positively correlated with duration of illness, TRV, LDH, serum ferritin, and negatively correlated with Hb levels. The strongest predictor for TRV was serum ferritin followed by the NT-pro-BNP level. Forty-six-point-seven percent of sickle cell disease patients with PH had either high or intermediate probability V/Q scan results compared to 10% of thalassemic patients with PH who had high probability V/Q scan results. Pulmonary hypertension is highly prevalent in young sickle cell disease and thalassemia patients, where elevated serum ferritin and NT-pro-BNP are the main indicators. PMID:20113292

  12. Prognostic value of N‐terminal pro‐B‐type natriuretic peptide for conservatively and surgically treated patients with aortic valve stenosis

    PubMed Central

    Weber, M; Hausen, M; Arnold, R; Nef, H; Moellman, H; Berkowitsch, A; Elsaesser, A; Brandt, R; Mitrovic, V; Hamm, C

    2006-01-01

    Objective To evaluate the prognostic value of N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) in patients with aortic stenosis being treated conservatively or undergoing aortic valve replacement (AVR). Methods 159 patients were followed up for a median of 902 days. 102 patients underwent AVR and 57 were treated conservatively. NT‐proBNP at baseline was raised in association with the degree of severity and of functional status. Results During follow up 21 patients (13%) died of cardiac causes or required rehospitalisation for decompensated heart failure. NT‐proBNP at baseline was higher in patients with an adverse outcome than in event‐free survivors (median 623 (interquartile range 204–1854) pg/ml v 1054 (687–2960) pg/ml, p  =  0.028). This difference was even more obvious in conservatively treated patients (331 (129–881) pg/ml v 1102 (796–2960) pg/ml, p  =  0.002). Baseline NT‐proBNP independently predicted an adverse outcome in the entire study group and in particular in conservatively treated patients (area under the curve (AUC)  =  0.65, p  =  0.028 and AUC  =  0.82, p  =  0.002, respectively) but not in patients undergoing AVR (AUC  =  0.544). At a cut‐off value of 640 pg/ml, baseline NT‐proBNP was discriminative for an adverse outcome. Conclusion NT‐proBNP concentration is related to severity of aortic stenosis and provides independent prognostic information for an adverse outcome. However, this predictive value is limited to conservatively treated patients. Thus, the data suggest that assessing NT‐proBNP may have incremental value for selecting the optimal timing of valve replacement. PMID:16740919

  13. Atrial natriuretic factor: is it responsible for hyponatremia and natriuresis in neurosurgery?

    PubMed Central

    Gasparotto, Ana Paula Devite Cardoso; Falcão, Antonio Luis Eiras; Kosour, Carolina; Araújo, Sebastião; Cintra, Eliane Araújo; de Oliveira, Rosmari Aparecida Rosa Almeida; Martins, Luiz Claudio; Dragosavac, Desanka

    2016-01-01

    Objective To evaluate the presence of hyponatremia and natriuresis and their association with atrial natriuretic factor in neurosurgery patients. Methods The study included 30 patients who had been submitted to intracranial tumor resection and cerebral aneurism clipping. Both plasma and urinary sodium and plasma atrial natriuretic factor were measured during the preoperative and postoperative time periods. Results Hyponatremia was present in 63.33% of the patients, particularly on the first postoperative day. Natriuresis was present in 93.33% of the patients, particularly on the second postoperative day. Plasma atrial natriuretic factor was increased in 92.60% of the patients in at least one of the postoperative days; however, there was no statistically significant association between the atrial natriuretic factor and plasma sodium and between the atrial natriuretic factor and urinary sodium. Conclusion Hyponatremia and natriuresis were present in most patients after neurosurgery; however, the atrial natriuretic factor cannot be considered to be directly responsible for these alterations in neurosurgery patients. Other natriuretic factors are likely to be involved. PMID:27410411

  14. Effect of natriuretic peptides on cerebral artery blood flow in healthy volunteers.

    PubMed

    Guo, Song; Goetze, Jens P; Jeppesen, Jørgen L; Burnett, John C; Olesen, Jes; Jansen-Olesen, Inger; Ashina, Messoud

    2015-12-01

    The natriuretic peptides (NPs), atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP), have vasoactive functions that concern humans and most animals, but their specific effects on cerebral circulation are poorly understood. We therefore examined the responsiveness of cerebral arteries to different doses of the natriuretic peptides in animals and humans. We conducted a dose-response experiment in guinea pigs (in vitro) and a double-blind, three-way cross-over study in healthy volunteers (in vivo). In the animal experiment, we administered cumulative doses of NPs to pre-contracted segments of cerebral arteries. In the main study, six healthy volunteers were randomly allocated to receive two intravenous doses of ANP, BNP or CNP, respectively, over 20 min on three separate study days. We recorded blood flow velocity in the middle cerebral artery (VMCA) by transcranial Doppler. In addition, we measured temporal and radial artery diameters, headache response and plasma concentrations of the NPs. In guinea pigs, ANP and BNP but not CNP showed significant dose-dependent relaxation of cerebral arteries. In healthy humans, NP infusion had no effect on mean VMCA, and we found no difference in hemodynamic responses between the NPs. Furthermore, natriuretic peptides did not affect temporal and radial artery diameters or induce headache. In conclusion, natriuretic peptides in physiological and pharmacological doses do not affect blood flow velocity in the middle cerebral artery or dilate extracerebral arteries in healthy volunteers. PMID:26417835

  15. Differences between the Pallas collisional family and similarly sized B-type asteroids

    NASA Astrophysics Data System (ADS)

    Alí-Lagoa, V.; Licandro, J.; Gil-Hutton, R.; Cañada-Assandri, M.; Delbo', M.; de León, J.; Campins, H.; Pinilla-Alonso, N.; Kelley, M. S. P.; Hanuš, J.

    2016-06-01

    Context. B-type asteroids constitute a peculiar spectral class within the C-complex. Previous work has pointed out the difference between the visible geometric albedos of B-types and those of the Pallas collisional family (PCF), whose few members with observed spectra are B-types (one exception out of eight objects). This has been interpreted as being due to compositional differences. However, the PCF members are typically smaller than the spectroscopically classified B-types, and the following possibilities have not been ruled out: the albedo differences might be related to a size-albedo dependence and/or to the generally larger errors of the WISE data and best-fitting values of the derived parameters expected for smaller objects. Aims: We compare albedos and beaming parameters of PCF members and B-types of similar sizes and re-examine our conclusion on the different composition of the PCF. Methods: By modelling their WISE/NEOWISE data, we derived sizes and albedos of all objects whose Sloan Digital Sky Survey reflectances are similar to the typical B-type reflectance spectra. In particular, we derived the so-called infrared beaming parameters (η), effective diameters (D), and corresponding visible geometric albedos (pV), and studied their value distributions. Results: We obtained the effective diameter and geometric visible albedo for ~600 B-type asteroids whose sizes range between 2 and 100 km, approximately half of which have fitted η-values that are inversely correlated to size. We found that the albedo distributions of the PCF is significantly different from that of other B-types in the same size range (2-20 km), and we rule out any size-albedo dependency or biases related to the lower quality of the pV-values of smaller objects. In addition, we also found differences between the η-value distribution of the PCF and the other similarly-sized B-types. Conclusions: The differences in the visible albedos of PCF members and the other B-types of similar sizes is

  16. Porcine brain natriuretic peptide receptor in bovine adrenal cortex

    SciTech Connect

    Higuchi, K.; Hashiguchi, T.; Ohashi, M.; Takayanagi, R.; Haji, M.; Matsuo, H.; Nawata, H.

    1989-01-01

    The action of porcine brain natriuretic peptide (pBNP) on the steroidogenesis was investigated in cultured bovine adrenocortical cells. Porcine BNP induced a significant dose-dependent inhibition of both ACTH- and A II-stimulated aldosterone secretion. 10/sup /minus/8/M and 10/sup /minus/7/M pBNP also significantly inhibited ACTH-stimulated cortisol and dehydroepiandrosterone (DHEA) secretions. Binding studies of (/sup 125/I)-pBNP to bovine adrenocortical membrane fractions showed that adrenal cortex had high-affinity and low-capacity pBNP binding sites, with a dissociation constant (Kd) of 1.70 x 10/sup /minus/10/M and a maximal binding capacity (Bmax) of 19.9 fmol/mg protein. Finally, the 135 Kd radioactive band was specially visualized in the affinity labeling of bovine adrenal cortex with disuccinimidyl suberate (DSS). These results suggest that pBNP may have receptor-mediated suppressive actions on bovine adrenal steroidogenesis, similar to that in atrial natriuretic peptide (ANP).

  17. Natriuretic peptide control of energy balance and glucose homeostasis.

    PubMed

    Coué, Marine; Moro, Cedric

    2016-05-01

    Cardiac natriuretic peptides (NP) have recently emerged as metabolic hormones. Physiological stimulation of cardiac NP release as during exercise may contribute to increase fatty acid mobilization from adipose tissue and their oxidation by skeletal muscles. Clinical studies have shown that although very high plasma NP level characterizes cardiac dysfunction and heart failure, a consistently reduced plasma NP level is observed in metabolic diseases such as obesity and type 2 diabetes. A low circulating NP level also predicts the risk of new onset type 2 diabetes. It is unclear at this stage if the "natriuretic handicap" observed in obesity is causally associated with the incidence of type 2 diabetes. Recent work indicates that NP can activate a thermogenic program in brown and white fat, increase energy expenditure and inhibit food intake. Mouse studies also argue for a key role of NP in the regulation of energy balance and glucose homeostasis. This review will focus on recent human and mouse studies to highlight the metabolic roles of NP and their potential relevance in the context of obesity and type 2 diabetes. PMID:26037452

  18. Endothelial C-type natriuretic peptide maintains vascular homeostasis

    PubMed Central

    Moyes, Amie J.; Khambata, Rayomand S.; Villar, Inmaculada; Bubb, Kristen J.; Baliga, Reshma S.; Lumsden, Natalie G.; Xiao, Fang; Gane, Paul J.; Rebstock, Anne-Sophie; Worthington, Roberta J.; Simone, Michela I.; Mota, Filipa; Rivilla, Fernando; Vallejo, Susana; Peiró, Concepción; Sánchez Ferrer, Carlos F.; Djordjevic, Snezana; Caulfield, Mark J.; MacAllister, Raymond J.; Selwood, David L.; Ahluwalia, Amrita; Hobbs, Adrian J.

    2014-01-01

    The endothelium plays a fundamental role in maintaining vascular homeostasis by releasing factors that regulate local blood flow, systemic blood pressure, and the reactivity of leukocytes and platelets. Accordingly, endothelial dysfunction underpins many cardiovascular diseases, including hypertension, myocardial infarction, and stroke. Herein, we evaluated mice with endothelial-specific deletion of Nppc, which encodes C-type natriuretic peptide (CNP), and determined that this mediator is essential for multiple aspects of vascular regulation. Specifically, disruption of CNP leads to endothelial dysfunction, hypertension, atherogenesis, and aneurysm. Moreover, we identified natriuretic peptide receptor–C (NPR-C) as the cognate receptor that primarily underlies CNP-dependent vasoprotective functions and developed small-molecule NPR-C agonists to target this pathway. Administration of NPR-C agonists promotes a vasorelaxation of isolated resistance arteries and a reduction in blood pressure in wild-type animals that is diminished in mice lacking NPR-C. This work provides a mechanistic explanation for genome-wide association studies that have linked the NPR-C (Npr3) locus with hypertension by demonstrating the importance of CNP/NPR-C signaling in preserving vascular homoeostasis. Furthermore, these results suggest that the CNP/NPR-C pathway has potential as a disease-modifying therapeutic target for cardiovascular disorders. PMID:25105365

  19. Increased yield of high purity recombinant human brain natriuretic peptide by acid hydrolysis of short fusion partner in Escherichia coli.

    PubMed

    Kanumuri, Radha Madhavi; Bajji, Chitra; Tummuru, Rajesh R; Tatireddigari, Venkat R R Arva; Mangamoori, Lakshmi Narasu; Panati, Kalpana; Narala, Venkata Ramireddy

    2015-07-01

    Recombinant human B-type natriuretic peptide (rhBNP) is a 32-amino acid peptide used to treat congestive heart failure. In this paper, we report a method for the increased production of rhBNP in Escherichia coli with high purity. hBNP was cloned with a short growth hormone fusion partner coupled with a unique acid-labile dipeptide linker to cleave the fusion protein to release the rhBNP. The recombinant fusion protein was expressed as an inclusion body (IB) and the fermentation process was optimized to produce on large scale. The IBs were recovered by cell lysis, and the pure IBs were directly treated with diluted acid to get the target peptide from the fusion protein and the resultant peptide was purified by reversed phase chromatography. The final purity of the rhBNP was more than 99% with yield of 50mg per liter of culture, which is ten times higher than the previous reports. The purified rhBNP exhibited specific biological activity similar to the standard peptide in producing cyclic-guanosine monophosphate. PMID:25823948

  20. Comparison of usefulness of tissue Doppler imaging versus brain natriuretic peptide for differentiation of constrictive pericardial disease from restrictive cardiomyopathy.

    PubMed

    Sengupta, Partho P; Krishnamoorthy, Vijay K; Abhayaratna, Walter P; Korinek, Josef; Belohlavek, Marek; Sundt, Thoralf M; Chandrasekaran, Krishnaswamy; Seward, James B; Tajik, A Jamil; Khandheria, Bijoy K

    2008-08-01

    Brain (B-type) natriuretic peptide (BNP) and tissue Doppler imaging may distinguish restrictive cardiomyopathy (RCMP) from idiopathic constrictive pericardial disease (CP). However, their comparative efficacy is unknown for patients with CP from secondary causes (e.g., surgery or radiotherapy). We compared the efficacy of tissue Doppler imaging and BNP for differentiation of RCMP (n = 15) and CP (n = 16) were compared. BNP was higher in patients with RCMP than CP (p = 0.008), but the groups overlapped, particularly for BNP <400 pg/ml. BNP was lower with idiopathic CP than secondary CP (139 +/- 50 vs 293 +/- 69 pg/ml; p <0.001) or RCMP (139 +/- 50 vs 595 +/- 499 pg/ml; p <0.001), but not significantly different between those with secondary CP and RCMP (293 +/- 69 vs 595 +/- 499 pg/ml; p = 0.1). Patients with CP and RCMP had less overlap in early diastolic and isovolumic contraction tissue Doppler imaging velocities compared with BNP, with clear separation of groups evident with mean early diastolic annular velocities (averaged from 4 walls). Early diastolic tissue Doppler imaging velocity was superior to BNP for differentiation of CP and RCMP (area under the curve 0.97 vs 0.76, respectively; p = 0.01). In conclusion, mean early diastolic mitral annular velocity correctly distinguished CP from RCMP even when there was a large overlap of BNP between the 2 groups. PMID:18638602

  1. Increased plasma levels and blunted effects of brain natriuretic peptide in rats with congestive heart failure.

    PubMed

    Hoffman, A; Grossman, E; Keiser, H R

    1991-07-01

    The hemodynamic and renal effects of brain natriuretic peptide (BNP) were studied in conscious rats with experimental congestive heart failure (CHF) produced by an aortocaval fistula. The peptide had potent hypotensive, diuretic, and natriuretic effects in control rats, all of which were abolished in CHF. Plasma levels of BNP increased time-dependently during the development of CHF, and were more than four-fold higher in sodium retaining rats than in control rats. The data suggest that BNP secretion from the atria is increased in CHF, and that resistance to BNP, in addition to the relative resistance to atrial natriuretic factor, may contribute to sodium retention in CHF. PMID:1831369

  2. Dehydration breakdown of antigorite and the formation of B-type olivine CPO

    NASA Astrophysics Data System (ADS)

    Nagaya, Takayoshi; Wallis, Simon R.; Kobayashi, Hiroaki; Michibayashi, Katsuyoshi; Mizukami, Tomoyuki; Seto, Yusuke; Miyake, Akira; Matsumoto, Megumi

    2014-02-01

    Peridotite formed by contact metamorphism and dehydration breakdown of an antigorite schist from the Happo area, central Japan shows a strong olivine crystallographic preferred orientation (Ol CPO). The lack of mesoscale deformation structures associated with the intrusion and the lack of microstructural evidence for plastic deformation of neoblastic grains suggest that olivine CPO in this area did not form as a result of solid-state deformation. Instead, the good correspondence between the original antigorite orientation and the orientation of the newly formed olivine implies the CPO formed by topotactic growth of the olivine after antigorite. Ol CPO is likely to develop by a similar process in subduction zone environments where foliated serpentinite is dragged down to depths where antigorite is no longer stable. The Happo Ol CPO has a strong a-axis concentration perpendicular to the lineation and within the foliation-commonly referred to as B-type Ol CPO. Seismic fast directions parallel to the ocean trench are observed in many convergent margins and are consistent with the presence of B-type Ol CPO in the mantle wedge of these regions. Experimental work has shown that B-type CPO can form by dislocation creep under hydrous conditions at relatively high stresses. There are, however, several discrepancies between the characteristics of natural and laboratory samples with B-type Ol CPO. (1) The formation conditions (stress and temperature) of some natural examples with B-type CPO fall outside those predicted by experiments. (2) In deformation experiments, slip in the crystallographic c-axis direction is important but has not been observed in natural examples of B-type CPO. (3) Experimental work suggests the presence of H2O and either high shear stress or relatively low temperatures are essential for the formation of B-type CPO. These conditions are most likely to be achieved close to subduction boundaries, but these regions are also associated with serpentinization

  3. C-type natriuretic peptide in Parkinson's disease: reduced secretion and response to deprenyl.

    PubMed

    Espiner, E A; Dalrymple-Alford, J C; Prickett, T C R; Alamri, Y; Anderson, T J

    2014-04-01

    C-type natriuretic peptide (CNP) is a neurotrophic factor widely expressed in the central nervous system including the basal ganglia, limbic system and hypothalamus. Nothing is known of CNP's role in the human brain but in rodents CNP promotes axon growth and branching, and interacts with dopaminergic function in models of addiction. Because preliminary evidence showed reduced levels in Parkinson's disease (PD), we examined concentrations of CNP peptides in cerebrospinal fluid (CSF) in 146 PD patients from the DATATOP study to determine changes over time in relation to medication status and cognitive function. CNP and an aminoterminal product of proCNP (NTproCNP) were measured in extracts from stored CSF by radioimmunoassay. CSF samples were obtained twice-at enrolment and at the study's endpoint (requirement for levodopa treatment) after treatment with placebo or deprenyl. At enrolment, median baseline concentration of CSF NTproCNP (776 pmol/L, n = 146) was significantly lower than that in a reference group without neurological disorder (1,010 pmol/L, p < 0.001). Concentrations declined significantly during placebo (p = 0.02) and lower values at enrolment were associated with more rapid functional decline (p < 0.01). In contrast, deprenyl-a treatment which delayed the need for levodopa-nullified the time-dependent decline in CSF NTproCNP. In conclusion subnormal CSF NTproCNP which declines with time and associates with increasing functional disability implicates CNP in PD. Concordant clinical and peptide responses to deprenyl suggest that some of the benefits of monoamine oxidase inhibitors in PD are mediated by preserving tissue CNP activity. PMID:24306276

  4. Effectiveness of brain natriuretic peptide in predicting postoperative atrial fibrillation in patients undergoing non-cardiac thoracic surgery.

    PubMed

    Toufektzian, Levon; Zisis, Charalambos; Balaka, Christina; Roussakis, Antonios

    2015-05-01

    A best evidence topic was written according to a structured protocol. The question addressed was whether plasma brain natriuretic peptide (BNP) levels could effectively predict the occurrence of postoperative atrial fibrillation (AF) in patients undergoing non-cardiac thoracic surgery. A total of 14 papers were identified using the reported search, of which 5 represented the best evidence to answer the clinical question. The authors, date, journal, country, study type, population, outcomes and key results are tabulated. All studies were prospective observational, and all reported a significant association between BNP and N-terminal (NT)-proBNP plasma levels measured in the immediate preoperative period and the incidence of postoperative AF in patients undergoing either anatomical lung resections or oesophagectomy. One study reported a cut-off value of 30 pg/ml above which significantly more patients suffered from postoperative AF (P < 0.0001), while another one reported that this value could predict postoperative AF with a sensitivity of 77% and a specificity of 93%. Another study reported that patients with NT-proBNP levels of 113 pg/ml or above had an 8-fold increased risk of developing postoperative AF. These findings support that BNP or NT-proBNP levels, especially when determined during the preoperative period, if increased, are able to identify patients at risk for the development of postoperative AF after anatomical major lung resection or oesophagectomy. The same does not seem to be true for lesser lung resections. These high-risk patients might have a particular benefit from the administration of prophylactic antiarrhythmic therapy. PMID:25630332

  5. Cocoa flavanols reduce N‐terminal pro‐B‐type natriuretic peptide in patients with chronic heart failure

    PubMed Central

    De Palma, Rodney; Sotto, Imelda; Wood, Elizabeth G.; Khan, Noorafza Q.; Butler, Jane; Johnston, Atholl; Rothman, Martin T.

    2015-01-01

    Abstract Aims Poor prognosis in chronic heart failure (HF) is linked to endothelial dysfunction for which there is no specific treatment currently available. Previous studies have shown reproducible improvements in endothelial function with cocoa flavanols, but the clinical benefit of this effect in chronic HF has yet to be determined. Therefore, the aim of this study was to assess the potential therapeutic value of a high dose of cocoa flavanols in patients with chronic HF, by using reductions in N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) as an index of improved cardiac function. Methods and results Thirty‐two patients with chronic HF, stable on guideline‐directed medical therapy, were randomized to consume 50 g/day of high‐flavanol dark chocolate (HFDC; 1064 mg of flavanols/day) or low‐flavanol dark chocolate (LFDC; 88 mg of flavanols/day) for 4 weeks and then crossed over to consume the alternative dark chocolate for a further 4 weeks. Twenty‐four patients completed the study. After 4 weeks of HFDC, NT‐proBNP (mean decrease % ± standard deviation) was significantly reduced compared with baseline (−44 ± 69%), LFDC (−33 ± 72%), and follow‐up (−41 ± 77%) values. HFDC also reduced diastolic blood pressure compared with values after LFDC (−6.7 ± 10.1 mmHg). Conclusions Reductions in blood pressure and NT‐proBNP after HFDC indicate decreased vascular resistance resulting in reduced left ventricular afterload. These effects warrant further investigation in patients with chronic HF. PMID:27588209

  6. Relationship in humans between atrial natriuretic peptide and arginine vasopressin during dehydration

    SciTech Connect

    Burnett, J.C. Jr.; Wilson, D.M.; Kao, P.C.; Schwab, T.R.; Heublein, D.M.; Heser, D.W.

    1986-03-01

    The present study was designed to define in normal humans (n=6) the relationship between atrial natriuretic peptide (ANP) and arginine vasopressin (AVP) during thirty-six hours of dehydration. Atrial natriuretic peptide was measured from extracted plasma by radioimmunoassay to alpha-human atrial natriuretic peptide; arginine vasopressin was measured from platelet free plasma by specific radioimmunoassay to AVP. Determinations were obtained of ANP, AVP and plasma osmolality (Posm) prior to and following fluid deprivation for thirty-six hours. The present study demonstrates that dehydration in humans increases plasma osmolality and arginine vasopressin but does not increase atrial natriuretic peptide. These investigations importantly dissociate these two peptide hormonal systems during the physiologic adaptation to fluid deprivation.

  7. Natriuretic effect of naloxone in fasted, water-loaded rats.

    PubMed

    Walker, L A; Murphy, J C

    1984-01-01

    The influence of naloxone (10 mg/kg i.p.) on water and electrolyte excretion was assessed in water-loaded rats subjected to fasting or fasting and refeeding. In fed animals, naloxone had no effect on water or electrolyte excretion compared to saline injected controls. However, during fasting, which has been shown to activate endogenous opioid systems, naloxone had a marked natriuretic effect (43 +/- 10 vs. 11 +/- 4 muEq/100 g X 2 h, p less than 0.05). Naloxone increased the sodium excretion to a level not significantly different from fed animals. Potassium and water excretion were not significantly changed compared to saline injected rats. The results suggest that fasting activates a naloxone-sensitive mechanism for sodium retention, perhaps by increasing the release of endogenous opioid peptides, and that refeeding inhibits this mechanism. PMID:6539478

  8. Are endogenous cardenolides controlled by atrial natriuretic peptide.

    PubMed

    Brar, Kanwarjeet S; Gao, Yonglin; El-Mallakh, Rif S

    2016-07-01

    Endogenous cardenolides are digoxin-like substances and ouabain-like substances that have been implicated in the pathogenesis of hypertension and mood disorders in clinical and pre-clinical studies. Regulatory signals for endogenous cardenolides are still unknown. These endogenous compounds are believed to be produced by the adrenal gland in the periphery and the hypothalamus in the central nervous system, and constitute part of an hormonal axis that may regulate the catalytic activity of the α subunit of Na(+)/K(+)-ATPase. A review of literature suggests that there is great overlap in physiological environments that are associated with either elevations or reductions in the levels of atrial natriuretic peptide (ANP) and endogenous cardenolides. This suggests that these two factors may share a common regulatory signal or perhaps that ANP may be involved in the regulation of endogenous cardenolides. PMID:27241248

  9. Natriuretic peptides: diagnostic tools and predictors of heart failure outcome.

    PubMed

    Isakson, Susan R; Gardetto, Nancy J; Maisel, Alan S

    2006-11-01

    Congestive heart failure (CHF) is a progressive disease whose outcome largely depends on early, accurate and prompt diagnosis, accompanied by evidence-based treatment. The explosion of uptake of natriuretic peptides (NPs) in clinical practice belies an understanding of how peptides are used. The signal for NP release is the same signal that causes symptoms of CHF, such as increased wall stress. Thus, NPs can reliably add to the information a physician brings to the table as they attempt to diagnose the acutely dyspneic patient with CHF. Additionally, NPs have strong prognostic utility in the emergency room and the hospital. Monitoring of NPs during treatment for acute CHF may help manage the patient. In the future, it is possible that NPs will play a more prominent role in early detection of left ventricular dysfunction as well as guiding chronic CHF treatment. PMID:19804259

  10. Molecular evolution of shark C-type natriuretic peptides.

    PubMed

    Takano, M; Sasayama, Y; Takei, Y

    1994-06-01

    C-type natriuretic peptides (CNP) of varying length were isolated from the atrium or ventricle of a shark, Lamna ditropis and their amino acid sequences were determined. Although the sequence of Lamna CNP was highly homologous to those of other CNPs sequenced to date, the Lamna CNP-41, the longest CNP identified in this study, has one amino acid replacement from those of Triakis scyllia and Scyliorhinus canicula, and three amino acid replacements from that of Squalus acanthias. The degree of similarity of CNP molecules coincides well with their systematic positions in the cladogram of elasmobranchs; Lamna, Triakis and Scyliorhinus belong to the same order, but Lamna and Squalus belong to different orders. The facts that Lamna and Triakis are in different suborders but Triakis and Scyliorhinus are in the same suborder and have identical CNP-41, also support this evolutionary implication. PMID:7765421

  11. Neprilysin and Natriuretic Peptide Regulation in Heart Failure.

    PubMed

    Bayes-Genis, Antoni; Morant-Talamante, Nuria; Lupón, Josep

    2016-08-01

    Neprilysin is acknowledged as a key player in neurohormonal regulation, a cornerstone of modern drug therapy in chronic heart failure. In the cardiovascular system, neprilysin cleaves numerous vasoactive peptides, some with mainly vasodilating effects (natriuretic peptides, adrenomedullin, bradykinin) and other with mainly vasoconstrictor effects (angiotensin I and II, endothelin-1). For decades, neprilysin has been an important biotarget. Academia and industry have combined active efforts to search for neprilysin inhibitors (NEPIs) that might be useful in clinical practice. NEPI monotherapy was initially tested with little success due to efficacy issues. Next, combination of NEPI and ACE-inhibiting activity agents were abandoned due to safety concerns. Recently, the combination of NEPI and ARB, also known as ARNI, has shown better than expected results in heart failure with reduced ejection fraction, and multitude of ongoing studies are set to prove its value across the heart failure spectrum. PMID:27260315

  12. Atrial natriuretic peptide in cardiovascular biology and disease (NPPA).

    PubMed

    Song, Wei; Wang, Hao; Wu, Qingyu

    2015-09-10

    Atrial natriuretic peptide (ANP) is a cardiac hormone that regulates salt-water balance and blood pressure by promoting renal sodium and water excretion and stimulating vasodilation. ANP also has an anti-hypertrophic function in the heart, which is independent of its systemic blood pressure-lowering effect. In mice, ANP deficiency causes salt-sensitive hypertension and cardiac hypertrophy. Recent studies have shown that ANP plays an important role in regulating vascular remodeling and energy metabolism. Variants in the human NPPA gene, encoding the ANP precursor, are associated with hypertension, stroke, coronary artery disease, heart failure (HF) and obesity. ANP and related peptides are used as biomarkers for heart disease. Recombinant proteins and small molecules that enhance the ANP pathway have been developed to treat patients with HF. In this review, we discuss the role of ANP in cardiovascular biology and disease. PMID:26074089

  13. Natriuretic peptide C receptor signalling in the heart and vasculature

    PubMed Central

    Rose, Robert A; Giles, Wayne R

    2008-01-01

    Natriuretic peptides (NPs), including atrial, brain and C-type natriuretic peptides (ANP, BNP and CNP), bind two classes of cell surface receptors: the guanylyl cyclase-linked A and B receptors (NPR-A and NPR-B) and the C receptor (NPR-C). The biological effects of NPs have been mainly attributed to changes in intracellular cGMP following their binding to NPR-A and NPR-B. NPR-C does not include a guanylyl cyclase domain. It has been denoted as a clearance receptor and is thought to bind and internalize NPs for ultimate degradation. However, a substantial body of biochemical work has demonstrated the ability of NPR-C to couple to inhibitory G proteins (Gi) and cause inhibition of adenylyl cyclase and activation of phospholipase-C. Recently, novel physiological effects of NPs, mediated specifically by NPR-C, have been discovered in the heart and vasculature. We have described the ability of CNP, acting via NPR-C, to selectively inhibit L-type calcium currents in atrial and ventricular myocytes, as well as in pacemaker cells (sinoatrial node myocytes). In contrast, our studies of the electrophysiological effects of CNP on cardiac fibroblasts demonstrated an NPR-C–Gi–phospholipase-C-dependent activation of a non-selective cation current mediated by transient receptor potential (TRP) channels. It is also known that CNP and BNP have important anti-proliferative effects in cardiac fibroblasts that appear to involve NPR-C. In the mammalian resistance vessels, including mesenteric and coronary arteries, CNP has been found to function as an NPR-C-dependent endothelium-derived hyperpolarizing factor that regulates local blood flow and systemic blood pressure by hyperpolarizing smooth muscle cells. In this review we highlight the role of NPR-C in mediating these NP effects in myocytes and fibroblasts from the heart as well as in vascular smooth muscle cells. PMID:18006579

  14. Identification of Putative Natriuretic Hormones Isolated from Human Urine

    PubMed Central

    Kramer, Herbert J.

    2015-01-01

    This brief review describes some representative methodological approaches to the isolation of putative endogenous inhibitors of epithelial sodium transport – i.e., as ouabain-like factors (OLF) that inhibit the sodium transport enzyme Na-K-ATPase or inhibit the epithelial sodium channel (ENaC). Gel chromatography and reverse-phase (RP)-high performance liquid chromatography (HPLC) of lyophilized and reconstituted 24 h-urine from salt-loaded healthy humans led to two active fractions, a hydrophilic OLF-1 and a lipophilic OLF-2, whose mass (Ms)-spectroscopic data indicate a Mr of 391 (1, 2). Further identification was attempted by Ms-, infrared (IR)-, ultraviolet (UV)-, and 1H-NMR-spectroscopy. OLF-1 and OLF-2 may be closely related if not identical to (di)ascorbic acid or its salts such as vanadium (V)-Vv-diascorbate with Mr 403 (3) and VIV-diascorbate. OLF-1 and Vv-diascorbate are about 10-fold stronger inhibitors of Na-K-ATPase than OLF-2 and VIV-diascorbate, respectively. In conscious rats, i.v. infusion of OLF-1 and OLF-2 resulted in a strong natriuresis. In a similar study, Cain et al. (4) isolated a sodium transport inhibitor from the urine of uremic patients by gel chromatography and RP-HPLC. In uremic rats, a natriuretic response to the injection of the active material was found. Xanthurenic acid 8-O-β-d-glucoside (Mr 368) and xanthurenic acid 8-O-sulfate (Mr 284) were identified as endogenous inhibitors of sodium transport acting, e.g., by ENaC blockade. No definite relation to blood pressure, body fluid volume, or sodium balance has been reported for any of these above factors, and further studies to identify the natriuretic and/or ouabain-like compound(s) or hormone(s) will be needed. PMID:26052310

  15. Identification of Putative Natriuretic Hormones Isolated from Human Urine.

    PubMed

    Kramer, Herbert J

    2015-01-01

    This brief review describes some representative methodological approaches to the isolation of putative endogenous inhibitors of epithelial sodium transport - i.e., as ouabain-like factors (OLF) that inhibit the sodium transport enzyme Na-K-ATPase or inhibit the epithelial sodium channel (ENaC). Gel chromatography and reverse-phase (RP)-high performance liquid chromatography (HPLC) of lyophilized and reconstituted 24 h-urine from salt-loaded healthy humans led to two active fractions, a hydrophilic OLF-1 and a lipophilic OLF-2, whose mass (Ms)-spectroscopic data indicate a Mr of 391 (1, 2). Further identification was attempted by Ms-, infrared (IR)-, ultraviolet (UV)-, and (1)H-NMR-spectroscopy. OLF-1 and OLF-2 may be closely related if not identical to (di)ascorbic acid or its salts such as vanadium (V)-V(v)-diascorbate with Mr 403 (3) and V(IV)-diascorbate. OLF-1 and V(v)-diascorbate are about 10-fold stronger inhibitors of Na-K-ATPase than OLF-2 and V(IV)-diascorbate, respectively. In conscious rats, i.v. infusion of OLF-1 and OLF-2 resulted in a strong natriuresis. In a similar study, Cain et al. (4) isolated a sodium transport inhibitor from the urine of uremic patients by gel chromatography and RP-HPLC. In uremic rats, a natriuretic response to the injection of the active material was found. Xanthurenic acid 8-O-β-d-glucoside (Mr 368) and xanthurenic acid 8-O-sulfate (Mr 284) were identified as endogenous inhibitors of sodium transport acting, e.g., by ENaC blockade. No definite relation to blood pressure, body fluid volume, or sodium balance has been reported for any of these above factors, and further studies to identify the natriuretic and/or ouabain-like compound(s) or hormone(s) will be needed. PMID:26052310

  16. Comparison of the Degree of Exercise Tolerance in Children After Surgical Treatment of Complex Cardiac Defects, Assessed Using Ergospirometry and the Level of Brain Natriuretic Peptide

    PubMed Central

    Mazurek, Boguslaw; Szydlowski, Leslaw; Mazurek, Magdalena; Markiewicz-Loskot, Grazyna; Pajak, Jacek; Morka, Aleksandra

    2016-01-01

    Abstract Children who underwent surgery for complex congenital heart defects present worse exercise capacity than their healthy peers. In adults and adolescents, heart failure is assessed on the basis of clinical symptoms using the New York Heart Association (NYHA) score, while in an infant Ross scale; heart failure can also be evaluated by other parameters. The purpose of this study was to compare the degree of exercise tolerance in children after surgery for complex heart defects, assessed by the ratio of maximum oxygen uptake (VO2max) and the brain natriuretic peptide (N-terminal fragment of the prohormone brain-type natriuretic peptide [NT-proBNP]) concentration. The study group consisted of 42 children, ages 9 to 17 years (mean 14.00 ± 2.72). Among them there were 22 children with tetralogy of Fallot (ToF) after total correction, 18 children with transposition of the great arteries (d-TGA) after the arterial switch operation, and 2 children with single ventricle (SV) after the Fontan operation. All but 1 child were in NYHA class I. The control group consisted of 20 healthy children. Outcomes of interest were the ratio of VO2max, determined during ergospirometry, and the level of NT-proBNP. The statistical analysis was performed and the groups were considered significantly different for P < 0.05. There was no statistically significant correlation between NT-proBNP and maximum oxygen uptake (VO2) kg−1 min−1 in the study group compared with the control group. The VO2max in the test group had a mean value less (34.6 ± 8.0) than controls (38.4 ± 7.7), and the differences were statistically significant (P = 0.041). In contrast, the average concentration of NT-proBNP in the study group was higher than controls (117.9 ± 74.3 vs 18.0 ± 24.5), and these differences were statistically significant (P < 0.001). After operations for complex heart defects (ToF, TGA, and SV), children have worse heart function parameters and exercise

  17. Guanylyl Cyclase/Atrial Natriuretic Peptide Receptor-A: Role in the Pathophysiology of Cardiovascular Regulation

    PubMed Central

    Pandey, Kailash N.

    2012-01-01

    Atrial natriuretic factor (ANF), also known as atrial natriuretic peptide (ANP), is an endogenous and potent hypotensive hormone that elicits natriuretic, diuretic, vasorelaxant, and anti-proliferative effects, which are important in the control of blood pressure and cardiovascular events. One principal locus involved in the regulatory action of ANP and brain natriuretic peptide (BNP) is guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA). Studies on ANP, BNP, and their receptor, GC-A/NPRA, have greatly increased our knowledge of the control of hypertension and cardiovascular disorders. Cellular, biochemical, and molecular studies have helped to delineate the receptor function and signaling mechanisms of NPRA. Gene-targeted and transgenic mouse models have advanced our understanding of the importance of ANP, BNP, and GC-A/NPRA in disease states at the molecular level. Importantly, ANP and BNP are used as critical markers of cardiac events; however, their therapeutic potentials for the diagnosis and treatment of hypertension, heart failure, and stroke have just begun to be realized. We are now just at the initial stage of molecular therapeutics and pharmacogenomic advancement of the natriuretic peptides. More investigations should be undertaken and ongoing ones be extended in this important field. PMID:21815745

  18. Guanylyl cyclase / atrial natriuretic peptide receptor-A: role in the pathophysiology of cardiovascular regulation.

    PubMed

    Pandey, Kailash N

    2011-08-01

    Atrial natriuretic factor (ANF), also known as atrial natriuretic peptide (ANP), is an endogenous and potent hypotensive hormone that elicits natriuretic, diuretic, vasorelaxant, and anti-proliferative effects, which are important in the control of blood pressure and cardiovascular events. One principal locus involved in the regulatory action of ANP and brain natriuretic peptide (BNP) is guanylyl cyclase / natriuretic peptide receptor-A (GC-A/NPRA). Studies on ANP, BNP, and their receptor, GC-A/NPRA, have greatly increased our knowledge of the control of hypertension and cardiovascular disorders. Cellular, biochemical, and molecular studies have helped to delineate the receptor function and signaling mechanisms of NPRA. Gene-targeted and transgenic mouse models have advanced our understanding of the importance of ANP, BNP, and GC-A/NPRA in disease states at the molecular level. Importantly, ANP and BNP are used as critical markers of cardiac events; however, their therapeutic potentials for the diagnosis and treatment of hypertension, heart failure, and stroke have just begun to be realized. We are now just at the initial stage of molecular therapeutics and pharmacogenomic advancement of the natriuretic peptides. More investigations should be undertaken and ongoing ones be extended in this important field. PMID:21815745

  19. 2-Deoxy-d-Glucose (2-DG)-Induced Cardiac Toxicity in Rat: NT-proBNP and BNP as Potential Early Cardiac Safety Biomarkers.

    PubMed

    Terse, P S; Joshi, P S; Bordelon, N R; Brys, A M; Patton, K M; Arndt, T P; Sutula, T P

    2016-05-01

    2-Deoxy-d-glucose (2-DG) is being developed as a potential anticonvulsant and disease-modifying agent for patients with epilepsy; however, during preclinical development, cardiac toxicity has been encountered in rats. This study was performed to determine whether cardiac troponin (cTnI and cTnT), atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), N-terminal pro-brain natriuretic peptide (NT-proBNP), and/or creatine kinase (CK) could be useful as indicators of 2-DG cardiac toxicity. In addition, this study also investigated the association of cardiac histopathological changes with these biomarkers. F344 rats (4/sex/group/sacrifice point) were gavaged with either vehicle or 2-DG (50, 125, or 375 mg/kg twice daily; total daily dose of 100, 250, or 750 mg/kg/d) for 7, 14, 21, or 45 days followed by a 15-day recovery. Dose-dependent increases in NT-proBNP and BNP plasma concentrations were observed. Following recovery period, the NT-proBNP and BNP concentrations returned to baseline levels. There were no remarkable increases in CK, ANP, cTnI, or cTnT concentrations. There were no gross cardiac lesions observed at the necropsy. Microscopic findings of vacuolar degeneration and hypertrophy of the endothelial cells of the endocardium were present in the heart at doses of 250 and 750 mg/kg/d. Microscopic findings, in general, were associated with increases in NT-proBNP levels. Cardiac toxicity appeared to be reversible. In conclusion, NT-proBNP and BNP are potential early biomarkers for 2-DG-induced cardiac toxicity that can be useful to monitor 2-DG therapy in clinical trials. PMID:26838190

  20. Human adrenal tumor cell line SW-13 contains a natriuretic peptide receptor system that responds preferentially to ANP among various natriuretic peptides

    SciTech Connect

    Mizuno, T.; Katafuchi, T.; Hagiwara, H.; Ito, T.; Kangawa, K.; Matsuo, H.; Hirose, S. )

    1990-12-31

    A new type of ANP receptor system which clearly distinguishes natriuretic peptides A and B (ANP and BNP) has been identified in the human adrenal tumor cell line SW-13 and characterized. SW-13 cells responded to nanomolar concentrations of ANP with large increases in cGMP levels but in the case of BNP, much higher concentrations were required to produce the same extent of response. This property is unique since the 140-kDa ANP receptors so far characterized do not discriminate between ANP and BNP. For comparison, various natriuretic peptide receptors were also re-characterized using the recently identified CNP.

  1. A luminescence study of B-type Eu2O3 under pressure

    NASA Astrophysics Data System (ADS)

    Chen, G.; Stump, N. A.; Haire, R. G.; Burns, J. B.; Peterson, J. R.

    1994-07-01

    Luminescence spectra from Eu3+ ion in B-type (monoclinic) Eu2O3 powder have been recorded at room temperature as a function of pressure using a diamond anvil cell. Changes in the spectral pattern of the Eu3+ ion emission at about 4 GPa indicated that a phase transition to the A-type (hexagonal) structure had taken place. Upon release of the applied pressure, the B-type structure was regained with hysteresis. The spectral shifts with pressure have been used to study the effect of pressure on the spin-orbit interaction of the 4f electrons in the Eu3+ ion.

  2. Insulin/glucose induces natriuretic peptide clearance receptor in human adipocytes: a metabolic link with the cardiac natriuretic pathway.

    PubMed

    Bordicchia, M; Ceresiani, M; Pavani, M; Minardi, D; Polito, M; Wabitsch, M; Cannone, V; Burnett, J C; Dessì-Fulgheri, P; Sarzani, R

    2016-07-01

    Cardiac natriuretic peptides (NP) are involved in cardiorenal regulation and in lipolysis. The NP activity is largely dependent on the ratio between the signaling receptor NPRA and the clearance receptor NPRC. Lipolysis increases when NPRC is reduced by starving or very-low-calorie diet. On the contrary, insulin is an antilipolytic hormone that increases sodium retention, suggesting a possible functional link with NP. We examined the insulin-mediated regulation of NP receptors in differentiated human adipocytes and tested the association of NP receptor expression in visceral adipose tissue (VAT) with metabolic profiles of patients undergoing renal surgery. Differentiated human adipocytes from VAT and Simpson-Golabi-Behmel Syndrome (SGBS) adipocyte cell line were treated with insulin in the presence of high-glucose or low-glucose media to study NP receptors and insulin/glucose-regulated pathways. Fasting blood samples and VAT samples were taken from patients on the day of renal surgery. We observed a potent insulin-mediated and glucose-dependent upregulation of NPRC, through the phosphatidylinositol 3-kinase pathway, associated with lower lipolysis in differentiated adipocytes. No effect was observed on NPRA. Low-glucose medium, used to simulate in vivo starving conditions, hampered the insulin effect on NPRC through modulation of insulin/glucose-regulated pathways, allowing atrial natriuretic peptide to induce lipolysis and thermogenic genes. An expression ratio in favor of NPRC in adipose tissue was associated with higher fasting insulinemia, HOMA-IR, and atherogenic lipid levels. Insulin/glucose-dependent NPRC induction in adipocytes might be a key factor linking hyperinsulinemia, metabolic syndrome, and higher blood pressure by reducing NP effects on adipocytes. PMID:27101299

  3. Down-regulation does not mediate natriuretic peptide-dependent desensitization of natriuretic peptide receptor (NPR)-A or NPR-B: guanylyl cyclase-linked natriuretic peptide receptors do not internalize.

    PubMed

    Fan, Danhua; Bryan, Paula M; Antos, Laura K; Potthast, Regine J; Potter, Lincoln R

    2005-01-01

    Natriuretic peptide receptor A (NPR-A/GC-A) and B (NPR-B/GC-B) are members of the transmembrane guanylyl cyclase family that mediate the effects of natriuretic peptides via the second messenger, cGMP. Despite numerous reports of these receptors being down-regulated in response to various pathological conditions, no studies have actually measured desensitization and receptor internalization in the same cell line. Furthermore, the ligand-dependent trafficking properties of NPR-A remain controversial, whereas nothing is known about the trafficking of NPR-B. In this report, we tested whether down-regulation explains the ligand-dependent desensitization of NPR-A and NPR-B and characterized their trafficking properties using a combination of hormone-binding and antibody-based assays. Quantitative partition analysis indicated that (125)I-atrial natriuretic peptide (ANP) was rapidly released into the medium after 293T cells stably expressing NPR-A were warmed from 4 degrees to 37 degrees C. High-performance liquid chromatography fractionation of medium supplemented with the protease inhibitor phosphoramidon indicated that the (125)I-ANP was mostly intact. In contrast, (125)I-ANP purified from medium bathing cells expressing NPR-C, a receptor known to internalize natriuretic peptides, was degraded. Cleavable biotinylation and noncleavable biotinylation assays indicated that neither NPR-A nor NPR-B was internalized or degraded in response to natriuretic peptide binding. In contrast, agonist-dependent internalization of a G protein-coupled receptor was clearly apparent in the same cell line. Finally, we show that NPR-A and NPR-B are desensitized in cells in which they are not internalized. We suggest that mechanisms other than receptor down-regulation account for the desensitization of NPR-A and NPR-B that occurs in response to various physiological and pathological stimuli. PMID:15459247

  4. A Cadmium-transporting P1B-type ATPase in Yeast Saccharomyces cerevisiae*

    PubMed Central

    Adle, David J.; Sinani, Devis; Kim, Heejeong; Lee, Jaekwon

    2014-01-01

    Detoxification and homeostatic acquisition of metal ions are vital for all living organisms. We have identified PCA1 in yeast Saccharomyces cerevisiae as an overexpression suppressor of copper toxicity. PCA1 possesses signatures of a P1B-type heavy metal-transporting ATPase that is widely distributed from bacteria to humans. Copper resistance conferred by PCA1 is not dependent on catalytic activity, but it appears that a cysteine-rich region located in the N terminus sequesters copper. Unexpectedly, when compared with two independent natural isolates and an industrial S. cerevisiae strain, the PCA1 allele of the common laboratory strains we have examined possesses a missense mutation in a predicted ATP-binding residue conserved in P1B-type ATPases. Consistent with a previous report that identifies an equivalent mutation in a copper-transporting P1B-type ATPase of a Wilson disease patient, the PCA1 allele found in laboratory yeast strains is nonfunctional. Overexpression or deletion of the functional allele in yeast demonstrates that PCA1 is a cadmium efflux pump. Cadmium as well as copper and silver, but not other metals examined, dramatically increase PCA1 protein expression through post-transcriptional regulation and promote subcellular localization to the plasma membrane. Our study has revealed a novel metal detoxification mechanism in yeast mediated by a P1B-type ATPase that is unique in structure, substrate specificity, and mode of regulation. PMID:17107946

  5. Physical properties of small B-type asteroids from SDSS and WISE data

    NASA Astrophysics Data System (ADS)

    Ali-Lagoa, V.; Licandro, J.; Delbo, M.; Gil-Hutton, R.; Cañada-Assandri, M.; de Leon, J.; Pinilla-Alonso, N.; Campins, H.

    2014-07-01

    In this work, we study the physical properties from WISE data (Wright et al. 2010, Mainzer et al. 2011, Masiero et al. 2011) of a list of asteroids whose Sloan Digital Sky Survey (SDSS) data are compatible with those of B types in terms of their negative visible slopes (see, for example, de Leon et al. 2012). This allows us to extend to smaller-sized objects the study of spectroscopic B-types carried out by Ali-Lagoa et al. (2013), where we concluded that the members of the Pallas collisional family (PCF) have significantly different geometric albedos than the rest of the B types. Grav et al. (2012) pointed out that, even though the small-end members of the Jupiter Trojans appear to have higher geometric visible albedos than their larger counterparts (see their Figure 3), this is actually an artifact caused by the natural spread of the errors of the smaller objects and that there is no strong trend between size and albedo for the Jupiter Trojans. This motivates us to examine --- in a different context, since we are not proposing an albedo-size dependency --- the possibility that the abovementioned difference between the PCF and the rest of spectroscopic B types may also be caused by the former being smaller than the latter, which would introduce potential biases and/or result from larger relative errors in the values of the geometric albedo, since it is derived from poorer-quality asteroid absolute magnitudes and best-fit radiometric diameters.

  6. ProMat

    Energy Science and Technology Software Center (ESTSC)

    2008-06-12

    ProMAT is a software tool for statistically analyzing data from enzyme-linked immunosorbent assay microarray experiments. The software estimates standard curves, sample protein concentrations and their uncertainties for multiple assays. ProMAT generates a set of comprehensive figures for assessing results and diagnosing process quality. The tool is available for Windows or Mac, and is distributed as open-source Java and R code

  7. Finite Strain in the Forearc Mantle: Testing the B-type Fabric Anisotropy Hypothesis

    NASA Astrophysics Data System (ADS)

    Kneller, E. A.; van Keken, P.; Karato, S.; Park, J.

    2005-12-01

    Seismic observations from many subduction zones show that the seismically fast direction is perpendicular to the direction of convergence. This is opposite of what is expected from models that assume flow is parallel to plate motion and the seismically fast axis of olivine [100] aligns sub-parallel to the shear direction (A-type fabric). Recent deformation experiments on olivine aggregates show that under low-temperature and high-stress conditions, the fast axis of olivine aligns sub-perpendicular to the shear direction (B-type fabric)(Jung and Karato, 2001; Katayama et al., 2004). B-type fabric has potential to explain convergence-perpendicular anisotropy in subduction zones with flow parallel to plate motion. Kneller et al. (2005) used combined data from deformation experiments on olivine aggregates and dynamical models of subduction zones to predict the distribution of B-type fabric in the mantle wedge. This study predicted that the forearc mantle has suitable thermal and stress conditions for B-type fabric and a rapid transition toward the backarc to conditions more suitable for other olivine fabrics. A vertical projection of the volcanic arc into the mantle wedge is predicted to mark the fabric transition between B-type and A-, E-, or C-type fabrics depending on water content. An important aspect not thoroughly investigated by our previous research is finite strain accumulation across the predicted fabric transition. In this study we present finite strain calculation for non-Newtonian subduction zone models with composite water-dependent rheology. This composite rheology includes experimentally based Peierls, dislocation, and diffusion creep. We predict greater than 100 % strain accumulation across 75 km for material traveling into the forearc mantle. This strain accumulation may be sufficient to produce a well developed B-type fabric. Furthermore, material enters the forearc mantle from a low-strain-rate thermal boundary layer at the base of the overriding

  8. ENaC is regulated by natriuretic peptide receptor-dependent cGMP signaling

    PubMed Central

    Guo, Lai-Jing; Alli, Abdel A.; Eaton, Douglas C.

    2013-01-01

    Epithelial sodium channels (ENaCs) located at the apical membrane of polarized epithelial cells are regulated by the second messenger guanosine 3′,5′-cyclic monophosphate (cGMP). The mechanism for this regulation has not been completely characterized. Guanylyl cyclases synthesize cGMP in response to various intracellular and extracellular signals. We investigated the regulation of ENaC activity by natriuretic peptide-dependent activation of guanylyl cyclases in Xenopus 2F3 cells. Confocal microscopy studies show natriuretic peptide receptors (NPRs), including those coupled to guanylyl cyclases, are expressed at the apical membrane of 2F3 cells. Single-channel patch-clamp studies using 2F3 cells revealed that atrial natriuretic peptide (ANP) or 8-(4-chlorophenylthio)-cGMP, but not C-type natriuretic peptide or cANP, decreased the open probability of ENaC. This suggests that NPR-A, but not NPR-B or NPR-C, is involved in the natriuretic peptide-mediated regulation of ENaC activity. Also, it is likely that a signaling pathway involving cGMP and nitric oxide (NO) are involved in this mechanism, since inhibitors of soluble guanylyl cyclase, protein kinase G, inducible NO synthase, or an NO scavenger blocked or reduced the effect of ANP on ENaC activity. PMID:23324181

  9. CD-NP, a chimeric natriuretic peptide for the treatment of heart failure.

    PubMed

    Rose, Robert A

    2010-03-01

    In development by Nile Therapeutics Inc, under license from the Mayo Foundation, CD-NP is a chimeric natriuretic peptide in which the 15-amino acid C-terminal tail of Dendroaspis natriuretic peptide is fused to the 22-amino acid human C-type natriuretic peptide. The rationale for its design was to create a peptide with the beneficial cardiovascular and renal effects of native natriuretic peptides, but without a clinically significant hypotensive response. CD-NP is able to bind to all three natriuretic peptide receptors (NPR-A, NPR-B and NPR-C) and, therefore, is unique in being able to increase cyclic guanosine monophosphate production downstream of both NPR-A and NPR-B. Animal studies and human trials demonstrated that CD-NP is safe and improves cardiovascular and renal function without inducing significant levels of hypotension. Preliminary data also suggest improved renal function in human heart failure patients. Ongoing clinical trials are needed to further validate CD-NP as an effective treatment option for heart failure. PMID:20178049

  10. Natriuretic peptides in relation to the cardiac innervation and conduction system.

    PubMed

    Hansson, Magnus

    2002-09-01

    During the past two decades, the heart has been known to undergo endocrine action, harbouring peptides with hormonal activities. These, termed "atrial natriuretic peptide (ANP)," "brain natriuretic peptide (BNP)," and "C-type natriuretic peptide (CNP)," are polypeptides mainly produced in the cardiac myocardium, where they are released into the circulation, producing profound hypotensive effects due to their diuretic, natriuretic, and vascular dilatory properties. It is, furthermore, well established that cardiac disorders such as congestive heart failure and different forms of cardiomyopathy are combined with increased expression of ANP and BNP, leading to elevated levels of these peptides in the plasma. Besides the occurrence of natriuretic peptides (NPs) in the ordinary myocardium, the presence of ANP in the cardiac conduction system has been described. There is also evidence of ANP gene expression in nervous tissue such as the nodose ganglion and the superior cervical ganglion of the rat, ganglia known to be involved in the neuronal regulation of the heart. Furthermore, in the mammalian heart, ANP appears to affect the cardiac autonomic nervous system by sympathoinhibitory and vagoexcitatory actions. This article provides an overview of the relationship between the cardiac conduction system, the cardiac innervation and NPs in the mammalian heart and provides data for the concept that ANP is also involved in neuronal cardiac regulation. PMID:12226807