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Sample records for serum b-type natriuretic

  1. 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

  2. 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

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. The Prognostic Value of Serum Levels of Heart-Type Fatty Acid Binding Protein and High Sensitivity C-Reactive Protein in Patients With Increased Levels of Amino-Terminal Pro-B Type Natriuretic Peptide

    PubMed Central

    Jeong, Ji Hun; Seo, Yiel Hea; Ahn, Jeong Yeal; Kim, Kyung Hee; Seo, Ja Young; Kim, Moon Jin; Lee, Hwan Tae

    2016-01-01

    Background Amino-terminal pro-B type natriuretic peptide (NT-proBNP) is a well-established prognostic factor in heart failure (HF). However, numerous causes may lead to elevations in NT-proBNP, and thus, an increased NT-proBNP level alone is not sufficient to predict outcome. The aim of this study was to evaluate the utility of two acute response markers, high sensitivity C-reactive protein (hsCRP) and heart-type fatty acid binding protein (H-FABP), in patients with an increased NT-proBNP level. Methods The 278 patients were classified into three groups by etiology: 1) acute coronary syndrome (ACS) (n=62), 2) non-ACS cardiac disease (n=156), and 3) infectious disease (n=60). Survival was determined on day 1, 7, 14, 21, 28, 60, 90, 120, and 150 after enrollment. Results H-FABP (P<0.001), NT-proBNP (P=0.006), hsCRP (P<0.001) levels, and survival (P<0.001) were significantly different in the three disease groups. Patients were divided into three classes by using receiver operating characteristic curves for NT-proBNP, H-FABP, and hsCRP. Patients with elevated NT-proBNP (≥3,856 pg/mL) and H-FABP (≥8.8 ng/mL) levels were associated with higher hazard ratio for mortality (5.15 in NT-proBNP and 3.25 in H-FABP). Area under the receiver operating characteristic curve analysis showed H-FABP was a better predictor of 60-day mortality than NT-proBNP. Conclusions The combined measurement of H-FABP with NT-proBNP provides a highly reliable means of short-term mortality prediction for patients hospitalized for ACS, non-ACS cardiac disease, or infectious disease. PMID:27374706

  9. Current and emerging issues with B-type natriuretic peptide. Roundtable discussion.

    PubMed

    Silver, Marc A; Rosendorff, Clive; Berkowitz, Robert; Peacock, W Franklin

    2005-01-01

    A brief panel discussion was held on March 23, 2005, in New York City following a live symposium for primary care physicians discussing the roles of B-type natriuretic peptide in a variety of cardiovascular diseases. The participants were Dr. Marc A. Silver, Advocate Christ Medical Center, Oak Lawn, IL; Dr. Clive Rosendorff, Mount Sinai School of Medicine, New York, NY and VA Medical Center, Bronx, NY; Dr. Robert Berkowitz, Hackensack University Medical Center, Hackensack, NJ; and Dr. W. Franklin Peacock IV, The Cleveland Clinic Department of Emergency Medicine, Cleveland, OH. Dr. Silver moderated the discussion. The panel gathered to review some of the questions that emerged from the symposium and the questions raised by the attendees. These are of interest and importance to all interested in heart failure and B-type natriuretic peptide.

  10. [The role of B type natriuretic peptide in the assessment of post myocardial infarction prognosis].

    PubMed

    Ben Halima, A; Ibn el Hadj, Z; Chrigui, R; Kammoun, I; Lefi, A; Chine, S; Gargouri, S; Keskes, H; Kachboura, S

    2006-10-01

    Recently cardiac peptides have received close attention as cardiovascular markers. Brain (B type) natriuretic peptide is a neurohormone synthesized predominantly in ventricular myocardium. Previous studies have shown that this hormone can provide prognostic information in patients with myocardial infarction. The aim of this review is to evaluate the impact of plasma levels of BNP on prediction of left ventricular ejection fraction and remodelling and major cardiac events after myocardial infarction.

  11. Localization of the human B-type natriuretic peptide precursor (NPPB) gene to chromosome 1p36

    SciTech Connect

    Arden, K.C.; Viars, C.S.; Weiss, S.

    1995-03-20

    Cardiac myocytes synthesize and secrete a family of peptide hormones with potent natriuretic, diuretic, and vasodilatory properties. These peptides are derived from precursor molecules that are encoded by two different genes, the atrial natriuretic peptide precursor A (NPPA) and the B-type natriuretic peptide or natriuretic peptide precursor B (NPPB). A human genomic clone for the NPPB gene was used to determine the chromosomal location of the NPPB gene. Analysis of Southern blot hybridization to DNAs from various somatic cell hybrids and fluorescence in situ hybridization allowed assignment of the NPPB locus to human chromosome 1p36. This location coincided with that of the NPPA locus; pulsed-field gel electrophoresis placed NPPA and NPPB within 50 kb of each other. This close chromosomal linkage, together with the conserved primary sequences and structural organization of the two natriuretic peptide precursor genes, suggests that the natriuretic peptide loci may have evolved from a common ancestor gene. 22 refs., 4 figs., 1 tab.

  12. Invasive and noninvasive correlations of B-type natriuretic peptide in patients with heart failure due to Chagas cardiomyopathy.

    PubMed

    Vilas-Boas, Fábio; Feitosa, Gilson Soares; Soares, Milena B P; Pinho-Filho, Joel Alves; Nascimento, Thais; Barojas, Marcos M; Andrade, Marcus V S; Ribeiro-Dos-Santos, Ricardo; Bocchi, Edimar

    2008-01-01

    Heart failure due to Chagas cardiomyopathy (HFCC) differs from failure with other etiologies because of the occurrence of intense inflammatory infiltrate and right ventricle compromise. This article investigates correlations of B-type natriuretic peptide (BNP) levels with parameters of severity in HFCC. Twenty-eight patients and 8 normal controls underwent heart catheterization and clinical and laboratory analyses. BNP levels were higher in patients with HFCC (P<.0001) and correlated with New York Heart Association (NYHA) class; right atrial pressure; wedge pressure; cardiac output; levels of serum sodium, hemoglobin, urea, and tumor necrosis factor-alpha; and ejection fraction. Interferon-gamma and transforming growth factor-beta did not correlate with BNP level. The authors conclude that BNP levels are elevated in patients experiencing HFCC, irrespective of NYHA class, and that the occurrence of HFCC correlates with severity of disease.

  13. 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

  14. 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

  15. Increased transcripts for B-type natriuretic peptide in spontaneously hypertensive rats. Quantitative polymerase chain reaction for atrial and brain natriuretic peptide transcripts.

    PubMed

    Dagnino, L; Lavigne, J P; Nemer, M

    1992-11-01

    The cardiac natriuretic peptide family includes atrial natriuretic factor and brain or B-type natriuretic peptide, also known as iso-atrial natriuretic factor (isoANF). Although these peptides contribute to cardiovascular homeostasis, their respective roles remain unclear. To study regulation of atrial natriuretic factor and isoANF gene expression during progression of hypertension, we developed a quantitative polymerase chain reaction protocol to measure their transcript level in spontaneously hypertensive rat (SHR) hearts. At the onset of hypertension, atrial natriuretic factor transcripts in 5-week-old SHR were 50% of those of age-matched Wistar-Kyoto (WKY) rats, whereas the level of isoANF transcripts was similar in atria and twofold higher in ventricles. Because atria are the major sites of atrial natriuretic factor gene expression and ventricles contribute predominantly to cardiac isoANF synthesis, total atrial natriuretic factor messenger RNA (mRNA) in the hearts of 5-week-old SHR was about 50% of that in WKY rats, and total isoANF mRNA content was already higher than in control rats. In left ventricles and ventricular septa, progression of hypertension led to a maximal increase of twofold and fourfold in atrial natriuretic factor and isoANF mRNA levels, respectively, with no detectable change in right ventricles. In the atria of older SHR, atrial natriuretic factor and isoANF mRNA levels were comparable to those of age-matched controls. These data indicate that, although increased blood pressure stimulates both atrial natriuretic factor and isoANF gene expression, regulation of the two natriuretic peptide genes is not temporally coordinated in all cardiac compartments. Furthermore, isoANF mRNA is already induced in the ventricles at the onset of the hypertensive stage, and in older SHR, the isoANF gene is hyperresponsive to progression of hypertension compared with atrial natriuretic factor. Thus, isoANF might represent a very sensitive marker of cardiac

  16. 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

  17. 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

  18. B-type natriuretic peptide modulates ghrelin, hunger, and satiety in healthy men.

    PubMed

    Vila, Greisa; Grimm, Gabriele; Resl, Michael; Heinisch, Birgit; Einwallner, Elisa; Esterbauer, Harald; Dieplinger, Benjamin; Mueller, Thomas; Luger, Anton; Clodi, Martin

    2012-10-01

    Chronic heart failure is accompanied by anorexia and increased release of B-type natriuretic peptide (BNP) from ventricular cardiomyocytes. The pathophysiological mechanisms linking heart failure and appetite regulation remain unknown. In this study, we investigated the impact of intravenous BNP administration on appetite-regulating hormones and subjective ratings of hunger and satiety in 10 healthy volunteers. Participants received in a randomized, placebo-controlled, crossover, single-blinded study (subject) placebo once and 3.0 pmol/kg/min human BNP-32 once administered as a continuous infusion during 4 h. Circulating concentrations of appetite-regulating peptides were measured hourly. Subjective ratings of hunger and satiety were evaluated by visual analog scales. BNP inhibited the fasting-induced increase in total and acylated ghrelin concentrations over time (P = 0.043 and P = 0.038, respectively). In addition, BNP decreased the subjective rating of hunger (P = 0.009) and increased the feeling of satiety (P = 0.012) when compared with placebo. There were no significant changes in circulating peptide YY, glucagon-like peptide 1, oxyntomodulin, pancreatic polypeptide, leptin, and adiponectin concentrations. In summary, our results demonstrate that BNP exerts anorectic effects and reduces ghrelin concentrations in men. These data, taken together with the known cardiovascular properties of ghrelin, support the existence of a heart-gut-brain axis, which could be therapeutically targeted in patients with heart failure and obesity.

  19. 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

  20. 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

  1. B-type natriuretic peptide to predict ductus intervention in infants <28 weeks.

    PubMed

    Czernik, Christoph; Lemmer, Julia; Metze, Boris; Koehne, Petra S; Mueller, Christian; Obladen, Michael

    2008-09-01

    Patent ductus arteriosus (PDA) is frequent in neonates with gestational age of less than 28 wk. Clinical and echocardiographic signs define hemodynamic significance of PDA, but do not reveal the need for PDA intervention in the first days of life. B-type natriuretic peptide (BNP) has been proposed as a screening tool for PDA in preterm infants. To determine whether BNP can predict the need for PDA intervention, plasma BNP was measured by chemiluminescence immunoassay in 67 preterm infants <28 wk (median 26) on the second day of life in a prospective blinded study. PDA intervention was based on specified clinical and echocardiographic findings. Twenty-four patients (intervention group) received treatment for PDA and 43 patients (controls) remained without intervention. BNP concentrations were higher in the intervention (median 1069 pg/mL) than in the control group (247 pg/mL, p < 0.001). BNP correlated positively with ductal size (R = 0.46, p < 0.001) and atrial/aortic root ratio (R = 0.54, p < 0.001). In conclusion, plasma BNP proved to be a good predictor for ductus intervention (area under the curve: 0.86) with the best cutoff at 550 pg/mL on the second day of life in ventilated infants less than 28 wk gestation (sensitivity: 83%; specificity: 86%).

  2. Cortical Brain Connectivity and B-Type Natriuretic Peptide in Patients With Congestive Heart Failure.

    PubMed

    Vecchio, Fabrizio; Miraglia, Francesca; Valeriani, Lavinia; Scarpellini, Maria Gabriella; Bramanti, Placido; Mecarelli, Oriano; Rossini, Paolo M

    2015-07-01

    The brain has a high level of complexity and needs continuous oxygen supply. So it is clear that any pathological condition, or physiological (aging) change, in the cardiovascular system affects functioning of the central nervous system. We evaluated linear aspects of the relationship between the slowness of cortical rhythms, as revealed by the modulation of a graph connectivity parameter, and congestive heart failure (CHF), as a reflection of neurodegenerative processes. Eyes-closed resting electroencephalographic (EEG) data of 10 patients with CHF were recorded by 19 electrodes positioned according the international 10-20 system. Graph theory function (normalized characteristic path length λ) was applied to the undirected and weighted networks obtained by lagged linear coherence evaluated by eLORETA software, therefore getting rid of volumetric propagation influences. The EEG frequency bands of interest were: delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), beta 2 (20-30 Hz), and gamma (30-40 Hz). The analysis between B-type natriuretic peptide (BNP) values and λ showed positive correlation in delta, associated with a negative correlation in alpha 2 band. Namely, the higher the severity of the disease (as revealed by the BNP vales), the higher the λ in delta, and lower in alpha 2 band. Results suggest that delta and alpha λ indices are good markers of the severity of CHF.

  3. 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

  4. 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

  5. N-terminal pro-B-type natriuretic peptide level inversely associates with metabolic syndrome in elderly persons

    PubMed Central

    2014-01-01

    Aims Serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) was lower in the general population with metabolic syndrome (MetS). The aim of this study was to evaluate the relationship between MetS and fasting serum NT-proBNP concentration in elderly persons. Methods Fasting blood samples were obtained from 84 elderly volunteers aged 65 years or older. MetS and its components were defined using diagnostic criteria from the International Diabetes Federation. Results Thirty-eight elderly persons (45.2%) had MetS. Fasting NT-proBNP level was negatively correlated with MetS among elderly patients (p = 0.001). Univariate linear regression analysis showed that age (r = 0.338; p = 0.002) was positively correlated with fasting serum log-NT-proBNP levels, while height (r = -0.253; p = 0.020), body weight (r = -0.238; p = 0.029), waist circumference (r = -0.270; p = 0.013), body fat mass (r = -0.356; p = 0.002) and triglyceride (r = -0.291; p = 0.007) were negatively correlated with fasting serum log-NT-proBNP levels among the elderly persons. Multivariate forward stepwise linear regression analysis of the significant variables showed that age (R 2 change = 0.114, p = 0.011), triglyceride (R 2 change = 0.118, p < 0.001), body fat mass (R 2 change = 0.084, p < 0.001), and height (R 2 change = 0.101, p < 0.001) were the independent predictor of fasting serum log-NT-proBNP levels in elderly persons. Conclusions NT-proBNP level is significantly reduced in elderly persons affected by MetS, and is significantly positively related to age, while negatively related to triglyceride, body fat mass, height in these subjects. PMID:24506889

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

    PubMed Central

    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 BCC

  7. 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

  8. 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.

  9. 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

  10. Diagnostic and prognostic values of B-type natriuretic peptides (BNP) and N-terminal fragment brain natriuretic peptides (NT-pro-BNP).

    PubMed

    Maries, Lorena; Manitiu, Ioan

    2013-08-01

    B-type natriuretic peptide (BNP) is a member of a fournatriuretic peptide family that shares a common 17-peptide ring structure. The N-terminal fragment (NT-pro-BNP) is biologically inert, but both are secreted in the plasma in equimolar quantities and both have been evaluated for use in the management of congestive heart failure. BNP and NT-pro-BNP are frequently used in the diagnosis of congestive heart failure and distinguishing between patients with dyspnoea of cardiac or pulmonary origin. Values of NT-pro-BNP are affected by age or the presence of one or several co-morbidities such as chronic renal failure, type 2 diabetes, and acute coronary syndrome. 'Normal' values of these peptides also vary depending on the type of test used. The performance characteristics of these tests vary depending on the patients on whom they are used and the manufacturer. For this reason, the determination of reference values for this peptide represents such a challenge.

  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. 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

  13. 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

  14. Impact of Preprocedural B-Type Natriuretic Peptide Levels on the Outcomes After Transcatheter Aortic Valve Implantation.

    PubMed

    Abramowitz, Yigal; Chakravarty, Tarun; Jilaihawi, Hasan; Lee, Chin; Cox, Justin; Sharma, Rahul P; Mangat, Geeteshwar; Cheng, Wen; Makkar, Raj R

    2015-12-15

    There are limited data on the effect of baseline B-type natriuretic peptide (BNP) on the outcome after transcatheter aortic valve implantation (TAVI). We investigated the influence of baseline BNP levels on the short-term and midterm clinical outcomes after TAVI. During a 3-year period, 780 patients with severe aortic stenosis underwent TAVI at our institute and had baseline BNP levels. We compared the high, mid, and low tertiles of BNP levels. TAVI end points, device success, and adverse events were considered according to the Valve Academic Research Consortium 2 definitions. Device success was significantly lower for patients with high BNP (98.1% vs 96.2% vs 91.9% for the low, mid, and high BNP tertiles, respectively; p = 0.003). All-cause mortality up to 30 days was 1.2% (3 of 260) versus 2.3% (6 of 260) versus 5% (13 of 260), respectively (p = 0.03). Six-month mortality rate was 4.1% (10 of 241) for the low BNP tertile, 5% (12 of 239) for the mid BNP tertile, and 17.1% (40 of 234) for the high BNP tertile (p <0.001). In the multivariate model, high tertile of baseline BNP was found to be significantly associated with all-cause mortality (hazard ratio 3.3, 95% confidence interval 1.64 to 6.48; p = 0.001). In conclusion, elevated BNP levels are associated with increased short-term and midterm mortality after TAVI. We recommend measurement of baseline BNP as part of risk stratification models for TAVI. PMID:26602075

  15. 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

  16. How well does B-type natriuretic peptide predict death and cardiac events in patients with heart failure: systematic review

    PubMed Central

    Doust, Jenny A; Pietrzak, Eva; Dobson, Annette; Glasziou, Paul

    2005-01-01

    Objective To assess how well B-type natriuretic peptide (BNP) predicts prognosis in patients with heart failure. Design Systematic review of studies assessing BNP for prognosis in patients with heart failure or asymptomatic patients. Data sources Electronic searches of Medline and Embase from January 1994 to March 2004 and reference lists of included studies. Study selection and data extraction We included all studies that estimated the relation between BNP measurement and the risk of death, cardiac death, sudden death, or cardiovascular event in patients with heart failure or asymptomatic patients, including initial values and changes in values in response to treatment. Multivariable models that included both BNP and left ventricular ejection fraction as predictors were used to compare the prognostic value of each variable. Two reviewers independently selected studies and extracted data. Data synthesis 19 studies used BNP to estimate the relative risk of death or cardiovascular events in heart failure patients and five studies in asymptomatic patients. In heart failure patients, each 100 pg/ml increase was associated with a 35% increase in the relative risk of death. BNP was used in 35 multivariable models of prognosis. In nine of the models, it was the only variable to reach significance—that is, other variables contained no prognostic information beyond that of BNP. Even allowing for the scale of the variables, it seems to be a strong indicator of risk. Conclusion Although systematic reviews of prognostic studies have inherent difficulties, including the possibility of publication bias, the results of the studies in this review show that BNP is a strong prognostic indicator for both asymptomatic patients and for patients with heart failure at all stages of disease. PMID:15774989

  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. 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

  19. 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

  20. 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

  1. 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

  2. Diagnostic, prognostic and therapeutic relevance of B-type natriuretic hormone and related peptides in children with congenital heart diseases.

    PubMed

    Cantinotti, Massimiliano; Giovannini, Stefania; Murzi, Bruno; Clerico, Aldo

    2011-04-01

    The aim of this article is to review the diagnostic and prognostic relevance of measurement of brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in pediatric patients with congenital cardiac diseases (CHD). A computerized literature search in the National Library of Medicine using the keywords "BNP assay" and "NT-proBNP assay"+neonate/s and newborn/s was performed. Next, we refined the analysis to include only the studies specifically designed to evaluate the clinical usefulness of BNP and NT-proBNP measurements in children with CHD. Several authors suggested that BNP/NT-proBNP is clinically helpful as a diagnostic and prognostic marker for children with suspected CHD. BNP values are age dependent, even in paediatric populations. Unfortunately, accurate reference values for BNP and NT-proBNP for neonatal ages have only recently become available. As a result, the lack of homogenous and accurate decisional levels in the neonatal period greatly limits the clinical impact of the BNP assay, and also contributed to the production of conflicting results. Regardless of age, there is great variability in BNP/NT-proBNP values among CHD characterized by different hemodynamic and clinical conditions. In particular, cardiac defects characterized by left ventricular volume and pressure overload usually show a higher BNP response than CHD which is characterized by right ventricular volume or pressure overload. BNP and NT-proBNP may be considered helpful markers in the integral clinical approach for patients with CHD. Measurement of BNP cannot replace cardiac imaging (including echocardiography, angiography and magnetic resonance), but provide independent, low cost and complementary information for the evaluation of cardiac function and clinical status.

  3. 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

  4. 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

  5. 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

  6. B-Type Natriuretic Peptide Deletion Leads to Progressive Hypertension, Associated Organ Damage, and Reduced Survival: Novel Model for Human Hypertension.

    PubMed

    Holditch, Sara J; Schreiber, Claire A; Nini, Ryan; Tonne, Jason M; Peng, Kah-Whye; Geurts, Aron; Jacob, Howard J; Burnett, John C; Cataliotti, Alessandro; Ikeda, Yasuhiro

    2015-07-01

    Altered myocardial structure and function, secondary to chronically elevated blood pressure, are leading causes of heart failure and death. B-type natriuretic peptide (BNP), a guanylyl cyclase A agonist, is a cardiac hormone integral to cardiovascular regulation. Studies have demonstrated a causal relationship between reduced production or impaired BNP release and the development of human hypertension. However, the consequences of BNP insufficiency on blood pressure and hypertension-associated complications remain poorly understood. Therefore, the goal of this study was to create and characterize a novel model of BNP deficiency to investigate the effects of BNP absence on cardiac and renal structure, function, and survival. Genetic BNP deletion was generated in Dahl salt-sensitive rats. Compared with age-matched controls, BNP knockout rats demonstrated adult-onset hypertension. Increased left ventricular mass with hypertrophy and substantially augmented hypertrophy signaling pathway genes, developed in young adult knockout rats, which preceded hypertension. Prolonged hypertension led to increased cardiac stiffness, cardiac fibrosis, and thrombi formation. Significant elongation of the QT interval was detected at 9 months in knockout rats. Progressive nephropathy was also noted with proteinuria, fibrosis, and glomerular alterations in BNP knockout rats. End-organ damage contributed to a significant decline in overall survival. Systemic BNP overexpression reversed the phenotype of genetic BNP deletion. Our results demonstrate the critical role of BNP defect in the development of systemic hypertension and associated end-organ damage in adulthood.

  7. Addition of N-terminal pro-B-type natriuretic peptide levels to electrocardiography criteria for detection of left ventricular hypertrophy: the ARIRANG study.

    PubMed

    Ahn, Min-Soo; Yoo, Byung-Su; Lee, Ji Hyun; Lee, Jun-Won; Youn, Young Jin; Ahn, Sung Gyun; Kim, Jang-Young; Lee, Seung-Hwan; Yoon, Junghan; Park, Jong-Ku; Ahn, Song Vogue; Choi, Eunhee

    2015-04-01

    The utility of electrocardiography (ECG) in screening for left ventricular hypertrophy (LVH) in general populations is limited mainly because its low sensitivity. B-type natriuretic peptide (BNP) is released due to the remodeling processes of LVH and could improve the diagnostic accuracy for the ECG criteria for LVH. We hypothesized that addition of BNP levels to ECG criteria could aid LVH detection compared with ECG alone in a general population. We enrolled consecutive 343 subjects from a community-based cohort. LVH was defined as LV mass index > 95 g/m(2) for females and > 115 g/m(2) for males according to echocardiography. The area under the receiver operator characteristic (ROC) curve to detect LVH was 0.55 (95% confidence interval [CI], 0.50-0.61) in Sokolow-Lyon criteria and 0.53 (0.47-0.59) in the Cornell voltage criteria. After addition of N-terminal-proBNP levels to the model, the corresponding areas under the ROC were 0.63 (0.58-0.69) and 0.64 (0.59-0.69), respectively. P values for the comparison in areas under the ROC for models with and without N-terminal-proBNP levels were < 0.001. These data suggest that addition of N-terminal-proBNP levels to ECG criteria could significantly improve the diagnostic accuracy of LVH in general populations.

  8. Hormone therapy with tamoxifen reduces plasma levels of NT-B-type natriuretic peptide but does not change ventricular ejection fraction after chemotherapy in women with breast cancer.

    PubMed

    Silva, F B; Romero, W G; Carvalho, A L R; Borgo, M V; Amorim, M H C; Gouvea, S A; Abreu, G R

    2015-02-01

    The objective of this study was to evaluate the effect of tamoxifen on the plasma concentration of NT-pro-B-type natriuretic peptide (NT-proBNP) in women undergoing chemotherapy for breast cancer and to correlate changes in NT-proBNP with the left ventricular ejection fraction (LVEF). Over a period of 12 months, we followed 60 women with a diagnosis of breast cancer. The patients were separated into a group that received only chemotherapy (n=23), a group that received chemotherapy + tamoxifen (n=21), and a group that received only tamoxifen (n=16). Plasma levels of NT-proBNP were assessed at 0 (T0), 6 (T6), and 12 (T12) months of treatment, and echocardiography data were assessed at T0 and T12. Plasma NT-proBNP levels were increased in the chemotherapy-only group at T6 and T12, whereas elevated NT-proBNP levels were only found at T6 in the chemotherapy + tamoxifen group. At T12, the chemotherapy + tamoxifen group exhibited a significant reduction in the peptide to levels similar to the group that received tamoxifen alone. The chemotherapy-only group exhibited a significant decrease in LVEF at T12, whereas the chemotherapy + tamoxifen and tamoxifen-only groups maintained levels similar to those at the beginning of treatment. Treatment with tamoxifen for 6 months after chemotherapy significantly reduced the plasma levels of NT-proBNP and did not change LVEF in women with breast cancer.

  9. B-type natriuretic peptide: powerful predictor of end-stage chronic heart failure in individuals with systolic dysfunction of the systemic right ventricle

    PubMed Central

    Hegarova, Marketa; Brotanek, Jaroslav; Kubanek, Milos; Kockova, Radka; Franekova, Janka; Lanska, Vera; Netuka, Ivan; Melenovsky, Vojtech; Malek, Ivan; Kautzner, Josef

    2016-01-01

    Aim To assess whether B-type natriuretic peptide (BNP) can serve as a predictor of end-stage chronic heart failure (CHF) in patients with severe systolic dysfunction of the systemic right ventricle (SRV). Methods We performed a retrospective analysis in 28 patients with severe systolic dysfunction of the SRV (ejection fraction 23 ± 6%) who were evaluated as heart transplant (HTx) candidates between May 2007 and October 2014. The primary endpoints of the study (end-stage CHF) were progressive CHF, urgent HTx, and ventricular assist device (VAD) implantation. Plasma BNP levels were measured using a chemiluminescent immunoassay. Results During median follow-up of 29 months (interquartile range, 9-50), 3 patients died of progressive CHF, 5 patients required an urgent HTx, and 6 patients underwent VAD implantation. BNP was a strong predictor of end-stage CHF (hazard ratio per 100 ng/L: 1.079, 95% confidence interval, 1.042-1.117, P˂0.001). The following variables with corresponding areas under the curve (AUC) were identified as the most significant predictors of end-stage CHF: BNP (AUC 1.00), New York Heart Association functional class class III or IV (AUC 0.98), decompensated CHF in the last year (AUC 0.96), and systolic dysfunction of the subpulmonal ventricle (AUC 0.96). Conclusion BNP is a powerful predictor of end-stage CHF in individuals with systolic dysfunction of the SRV. PMID:27586549

  10. Relationship between N-terminal pro-B-type natriuretic peptide and renal function: the effects on predicting early outcome after off-pump coronary artery bypass surgery

    PubMed Central

    Jo, Youn Yi; Kwak, Young Lan; Lee, Jonghoon

    2011-01-01

    Background Plasma levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) provide useful prognostic predictors in patients after cardiac surgery. However, predictive accuracy of NT-proBNP levels has varied significantly according to renal dysfunction. The purpose of this study was to assess whether preoperative NT-proBNP levels could be used as predictors of early postoperative outcomes on the basis of renal function in patients undergoing off-pump coronary artery bypass surgery (OPCAB). Methods In 219 patients undergoing elective OPCAB, NT-proBNP and an estimated glomerular filtration rate (eGFR) were assessed preoperatively. All patients were divided into 3 groups according to tertiles of eGFR: the first (eGFR ≥ 90 ml/min/1.73 m2), the second (90 ml/min/1.73 m2 > eGFR ≥ 72 ml/min/1.73 m2) and the third tertile group (eGFR < 72 ml/min/1.73 m2). End point was the composite of early postoperative complications defined as myocardial infarction, new onset atrial fibrillation, ventricular dysfunction, prolonged mechanical ventilator care (> 48 hr), prolonged ICU stay (≥ 3 days), and in hospital mortality. Results There was no difference in early postoperative complications among groups. A preoperative NT-proBNP level of 228 pg/ml and 302 pg/ml (sensitivity 70%, specificity 67%, P < 0.001 and sensitivity 73%, specificity 63%, P = 0.001, respectively) were optimal cut-off values predicting complicated early postoperative course in second and third tertile group, respectively. Conclusions Preoperative NT-proBNP levels seem to be predictive of early postoperative complications in patients with eGFR < 90 ml/min/1.73 m2 undergoing OPCAB. PMID:21860749

  11. Sensitive cardiac troponins and N-terminal pro-B-type natriuretic peptide in stable coronary artery disease: correlation with left ventricular function as assessed by myocardial strain.

    PubMed

    Smedsrud, Marit Kristine; Gravning, Jørgen; Omland, Torbjørn; Eek, Christian; Mørkrid, Lars; Skulstad, Helge; Aaberge, Lars; Bendz, Bjørn; Kjekshus, John; Edvardsen, Thor

    2015-06-01

    N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponins (cTns) measured with sensitive assays provide strong prognostic information in patients with stable coronary artery disease. However, the relationship between these biomarkers and myocardial contractile function, as well as infarct size, in this patient group, remains to be defined. The study population consisted of 160 patients referred to a follow-up echocardiography scheduled 1 year after coronary revascularization. Concentrations of NT-proBNP, high-sensitive cTnT (hs-cTnT) and sensitive cTnI assays were assessed. Left ventricular function was measured as global peak systolic longitudinal strain by speckle tracking echocardiography and infarct size was assessed by late-enhancement MRI. NT-proBNP and sensitive cTnI levels were significantly associated with left ventricular function by peak systolic strain (R-values 0.243 and 0.228, p = 0.002 and 0.004) as well as infarct size (R-values 0.343 and 0.366, p = 0.014 and p = 0.008). In contrast, hs-cTnT did not correlate with left ventricular function (R = 0.095, p = 0.231) and only marginally with infarct size (R = 0.237, p = 0.094). NT-proBNP and sensitive cTnI levels correlate with left ventricular function and infarct size in patients with stable coronary artery disease after revascularization. As opposed to hs-cTnT, NT-proBNP and cTnI seem to be indicators of incipient myocardial dysfunction and the extent of myocardial necrosis.

  12. 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

  13. Relationship between glomerular filtration rate and plasma N-terminal pro B-type natriuretic peptide concentrations in dogs with chronic kidney disease.

    PubMed

    Miyagawa, Y; Tominaga, Y; Toda, N; Takemura, N

    2013-08-01

    Plasma N-terminal pro B-type natriuretic peptide (NT-proBNP) concentrations increase in dogs with azotemia. However, the correlation between glomerular filtration rate (GFR) and NT-proBNP concentrations in dogs has not been evaluated. The objective of this study was to evaluate the correlation between GFR and plasma NT-proBNP concentrations in dogs with chronic kidney disease (CKD). In this retrospective cross-sectional study, plasma creatinine (Cre) and NT-proBNP concentrations, plasma iohexol clearance (PCio) values and blood pressure were measured in dogs with CKD. Dogs were classified according to PCio values into D group (dogs with decreased PCio values), and N group (dogs with normal PCio values). Dogs were further categorized on the basis of their systolic blood pressure and PCio values into NT-D group (normotensive dogs with decreased PCio values), NT-N group (normotensive dogs with normal PCio values), HT-D group (hypertensive dogs with decreased PCio values) and HT-N group (hypertensive dogs with normal PCio values). Significant correlations were observed between plasma NT-proBNP and Cre concentrations (r=0.360, P<0.05) and PCio values (r=-0.470, P<0.01). Plasma NT-proBNP concentrations were significantly higher in the D group than in the N group (P<0.001). Plasma NT-proBNP concentrations were significantly higher in the HT-D group than in the other three groups (P ≤ 0.007). No differences in plasma NT-proBNP concentrations were observed between the NT-D and HT-N groups (P=0.28). Plasma NT-proBNP concentrations were significantly lower in the NT-N group than in the other three groups (P ≤ 0.043). Our findings suggest that decreased GFR might be associated with increased plasma NT-proBNP concentrations in dogs, similar to that in humans. In addition, the complication of hypertension in CKD might be associated with further increases in plasma NT-proBNP concentrations. In conclusion, the effects of GFR and blood pressure on the plasma NT

  14. N-Terminal Pro-B-Type Natriuretic Peptide Plasma Levels as a Potential Biomarker for Cardiac Damage After Radiotherapy in Patients With Left-Sided Breast Cancer

    SciTech Connect

    D'Errico, Maria P.; Grimaldi, Luca; Petruzzelli, Maria F.; Gianicolo, Emilio A.L.; Tramacere, Francesco; Monetti, Antonio; Placella, Roberto; Pili, Giorgio; Andreassi, Maria Grazia; Sicari, Rosa; Picano, Eugenio; Portaluri, Maurizio

    2012-02-01

    Purpose: Adjuvant radiotherapy (RT) after breast-conserving surgery has been associated with increased cardiovascular mortality. Cardiac biomarkers may aid in identifying patients with radiation-mediated cardiac dysfunction. We evaluated the correlation between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and troponin (TnI) and the dose of radiation to the heart in patients with left-sided breast cancer. Methods and Materials: NT-proBNP and TnI plasma concentrations were measured in 30 left-sided breast cancer patients (median age, 55.0 years) 5 to 22 months after RT (Group I) and in 30 left-sided breast cancer patients (median age, 57.0 years) before RT as control group (Group II). Dosimetric and geometric parameters of heart and left ventricle were determined in all patients of Group I. Seventeen patients underwent complete two-dimensional echocardiography. Results: NT-proBNP levels were significantly higher (p = 0.03) in Group I (median, 90.0 pg/ml; range, 16.7-333.1 pg/ml) than in Group II (median, 63.2 pg/ml; range, 11.0-172.5 pg/ml). TnI levels remained below the cutoff threshold of 0.07 ng/ml in both groups. In patients with NT-proBNP values above the upper limit of 125 pg/ml, there were significant correlations between plasma levels and V{sub 3Gy}(%) (p = 0.001), the ratios D{sub 15cm{sup 3}}(Gy)/D{sub mean}(Gy) (p = 0.01), the ratios D{sub 15cm}{sup 3}/D{sub 50%} (Gy) (p = 0.008) for the heart and correlations between plasma levels and V{sub 2Gy} (%) (p = 0.002), the ratios D{sub 1cm{sup 3}}(Gy)/D{sub mean}(Gy) (p = 0.03), and the ratios D{sub 0.5cm{sup 3}}(Gy)/D{sub 50%}(Gy) (p = 0.05) for the ventricle. Conclusions: Patients with left-sided breast cancer show higher values of NT-pro BNP after RT when compared with non-RT-treated matched patients, increasing in correlation with high doses in small volumes of heart and ventricle. The findings of this study show that the most important parameters are not the mean doses but instead the small

  15. Elevated serum brain natriuretic peptide and matrix metalloproteinases 2 and 9 in Wilson's disease.

    PubMed

    Cheng, Nan; Wang, Honghao; Dong, Jianjian; Pan, Suyue; Wang, Xun; Han, Yongsheng; Han, Yongzhu; Yang, Renmin

    2015-08-01

    Wilson's disease (WD) is a disease of copper metabolism characterized by excessive copper deposition in the body. It is reported abnormal copper metabolism has been associated with cardiovascular disease. BNP and MMP2/9 were biomarkers of congestive heart failure (CHF). There is rare study to explore whether serum concentrations of BNP, MMP2, and or MMP9 are altered in patients with WD. In this study we determine whether serum concentrations of brain natriuretic peptide (BNP) and matrix metalloproteinases (MMP) 2 and 9 are increased in patients with WD. Serum BNP, MMP2 and MMP9 were measured by an ELISA in 34 patients with hepatic WD, in 68 patients with neurological WD, and in 33 healthy controls. We found serum BNP levels were higher in patients with neurological WD than in healthy controls (p = 0.033). Serum MMP2 levels were higher in patients with hepatic (p = 0.009) and neurologic (p = 0.0004) WD than in controls. Serum MMP9 levels were higher in patients with neurologic WD than in patients with hepatic WD (p = 0.002) and controls (p = 0.00005), and were higher in patients with hepatic WD than in controls (p = 0.03). Serum BNP levels were negatively correlated with ceruloplasmin (p = 0.017, r = -0.215), while serum (p = 0.019, r = -0.221) and MMP9 (p = 0.011, r = -0.231) in patients with WD were negatively correlated with ceruloplasmin. BNP, MMP2, and MMP9 may reflect the deposition of copper in the heart.

  16. Association of N-terminal pro-B-type natriuretic peptide with contrast-induced nephropathy and long-term outcomes in patients with chronic kidney disease and relative preserved left ventricular function.

    PubMed

    Liu, Yuan-hui; Liu, Yong; Zhou, Ying-ling; Yu, Dan-qing; He, Peng-cheng; Xie, Nian-jin; Li, Hua-long; Wei-Guo; Chen, Ji-yan; Tan, Ning

    2015-04-01

    The aim of the present article was to evaluate the association of N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) with contrast-induced nephropathy (CIN) and long-term outcomes in patients with chronic kidney disease (CKD) and relative preserved left ventricular function (LVF) undergoing percutaneous coronary intervention (PCI). We prospectively enrolled 1203 consecutive patients with CKD and preserved LVF undergoing elective PCI. The primary end point was the development of CIN, defined as an absolute increase in serum creatinine (SCr) ≥0.5 mg/dL, from baseline within 48 to 72 hours after contrast medium exposure. CIN incidence varied from 2.2% to 5.2%. Univariate logistic analysis showed that lg-NT-pro-BNP was significantly associated with CIN (odds ratio [OR] = 3.93, 95% confidence interval [CI], 2.22-6.97, P < 0.001). Furthermore, lg-NT-pro-BNP remained a significant predictor of CIN (OR = 3.30, 95% CI, 1.57-6.93, P = 0.002), even after adjusting for potential confounding risk factors. These results were confirmed by using other CIN criteria, which were defined as elevations of the SCr by 25% or 0.5 and 0.3 mg/dL from the baseline. The best cutoff value of lg-NT-pro-BNP for detecting CIN was 2.73 pg/mL (537 pg/mL) with 73.1% sensitivity and 70.0% specificity according to the receiver operating characteristic (ROC) analysis (C statistic = 0.754, 95% CI, 0.67-0.84, P < 0.001). In addition, NT-pro-BNP ≥537 pg/mL (2.73 pg/mL, lg-NT-pro-BNP) was associated with an increased risk of all-cause mortality and composite end points during 2.5 years of follow-up. NT-pro-BNP ≥537 pg/mL is independently associated with an increased risk of CIN with different definitions and poor clinical outcomes in patients with CKD and relative preserved LVF undergoing PCI. PMID:25837748

  17. 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

  18. Analytical performance of the N terminal pro B type natriuretic peptide (NT-proBNP) assay on the Elecsys 1010 and 2010 analysers.

    PubMed

    Collinson, P O; Barnes, S C; Gaze, D C; Galasko, G; Lahiri, A; Senior, R

    2004-03-15

    The Elecsys NT-proBNP assay is based on two polyclonal antibodies directed at residues 1-21 and 39-50 of the NT-proBNP molecule. Analytical performance was assessed using NCCLS protocol EP-5A using three serum pools in a preliminary study then as part of a multicentre evaluation (16 instruments in 8 hospitals). Using pools of 350 pg/l, 8700 pg/l and 13000 pg/l single site within run %CV was 0.7-1.6 (1010) and 1.2-1.5 (2010) and between run CV 5.3-6.7 (1010) and 4.4-5.0 (2010). In the multicentre evaluation within run CV was 1.0-2.5% with total imprecision 1.5-2.5% and between labs imprecision 3.8-4.0%. Functional sensitivity of <50 pg/l and measuring range to 35000 pg/l. There was excellent agreement between instrument platforms, y=0.97x+2.6; r=1.00 (n=215) for Elecsys 2010 (x) vs. Elecsys 1010 (y) and y=1.02x-0.3; r=1.00 (n=99) for Elecsys 2010 (x) vs. E 170 (y). Serum and heparin plasma samples showed good agreement but lower values were seen in EDTA plasma. Samples were stable for 7 days at room temperature; 21 days at 4 degrees C and for 5 freeze thaw cycles. Samples were obtained from a population of 1205 (671 male, 534 female) apparently healthy individuals screened by echocardiography and symptom questionnaire. There was poor correlation with NT-proANP (ELISA) (rs 0.33) and modest correlation with BNP (rs 0.89) with NT-proBNP values approximately 5 times greater than BNP (Biosite Triage). In a subset of 320 with normal ejection fraction (>50%) and no risk factors, NT-proBNP values increased with age and were higher in women than men.

  19. Evaluation of cardiac functions of cirrhotic children using serum brain natriuretic peptide and tissue Doppler imaging

    PubMed Central

    Fattouh, Aya M; El-Shabrawi, Mortada H; Mahmoud, Enas H; Ahmed, Wafaa O

    2016-01-01

    Background: Cirrhotic cardiomyopathy (CCM) is described as the presence of cardiac dysfunction in cirrhotic patients. In children with chronic liver disease, CCM has been very rarely investigated. The Aim of the Study: Is to evaluate the cardiac function of cirrhotic children to identify those with CCM. Patients and Methods: Fifty-two cirrhotic patients and 53 age and sex matched controls were assessed using serum brain-type natriuretic peptide (BNP), conventional echocardiography, and tissue Doppler imaging. Results: Patients’ mean ages were 7.66 ± 4.16 years (vs. 6.88 ± 3.04 years for the controls). The study included 27 males and 25 females (28 and 25 respectively for the controls). Patients had larger left atrium and right ventricle (RV) (P value 0.05) and increased LV posterior wall thickness than controls (P value 0.04). They had higher late atrial diastolic filling velocity (A) of tricuspid valve (TV) inflow (0.59 ± 0.17 vs. 0.5 ± 0.1 m/s, P < 0.001) and lower ratios between the early diastolic filling velocity (E) and A wave velocity (E/A) of both mitral valve and TV inflow (1.7 ± 0.35 vs. 1.87 ± 0.34 and 1.3 ± 0.3 vs. 1.5 ± 0.3, P < 0.005 and 0.0008, respectively). Patients had significantly longer isovolumic relaxation time of LV (45.5 ± 11.1 vs. 40.5 ± 7.7 ms P 0.008), higher late diastolic peak myocardial velocity (A’) (11.8 ± 3.6 vs. 9.5 ± 2.7 ms, P 0.0003) and systolic velocity (S’) of the RV (14.5 ± 2.7 vs. 13.2 ± 2.9, P 0.01) and significantly higher myocardial performance index of both LV and RV (P 0.001 and 0.01). BNP levels were significantly higher in cases than controls (5.25 ng/l vs. 3.75 ng/l, P < 0.04) and was correlated with the E wave velocity of the TV (r 0.004) and the E/E’ ratio of the RV (r 0.001). None of the clinical or laboratory data were correlated with the BNP level. Conclusion Cirrhotic children have cardiac dysfunction mainly in the form of diastolic dysfunction. There is a need that CCM be more accurately

  20. Predictive Value of Admission N-Terminal Pro-B-Type Natriuretic Peptide and Renal Function in Older People Hospitalized for Dyspnoea

    PubMed Central

    De Giorgi, Alfredo; Pala, Marco; Zuliani, Giovanni

    2013-01-01

    Background. We investigated the relationship between NT-pro-BNP, glomerular filtration rate (GFR), and all-cause mortality rates in a cohort of older people discharged from an internal medicine unit after admission for dyspnoea. Patients and Methods. NT-pro-BNP was evaluated in serum samples of 134 patients aged 80 ± 6 years who presented to a single academic centre with worsening dyspnoea. History data and anthropometric, clinical, and biochemical parameters including GFR were collected at the time of admission. 119 out of 134 were discharged alive from hospital and were included in the follow-up of 779 ± 370 days. Results. 35 out of 119 subjects died after a follow-up of 266 ± 251 days. Cox proportional hazards model showed that GFR and Ln (NT-pro-BNP) were predictors for all-cause mortality with estimated hazard ratios of 0.969 (95% confidence interval: 0.950–0.988; P = 0.001) and 2.360 (95% confidence interval: 1.208–4.610; P = 0.012), respectively. Patients characterized by high NT-pro-BNP levels and GFR ≥ 60 mL/min/1.73 m2 showed a dramatic reduction in survival duration compared with the groups with different combinations of the two variables (P = 0.008). Conclusions. In the elderly, NT-pro-BNP and GFR are predictors of all-cause mortality after admission because of dyspnoea. Since the fact that subjects with high NT-pro-BNP and GFR ≥ 60 mL/min/1.73 m2 exhibited a reduced survival, high admission NT-pro-BNP suggests future negative outcome. PMID:24324290

  1. Predictive Role of Intraoperative Serum Brain Natriuretic Peptide for Early Allograft Dysfunction in Living Donor Liver Transplantation.

    PubMed

    Chae, Min Suk; Koo, Jung Min; Park, Chul Soo

    2016-01-01

    BACKGROUND Early allograft dysfunction (EAD) is considered an important complication in liver transplantation. Serum brain natriuretic peptide (BNP) is a marker of cardiac dysfunction related to end-stage liver disease. We investigated the intraoperative change in the serum BNP level and its contribution to EAD after living donor liver transplantation (LDLT). MATERIAL AND METHODS The perioperative data of 104 patients who underwent LDLT were retrospectively reviewed and compared between patients with and without EAD. Serum BNPs were obtained at each phase, and potentially significant factors (P<0.1) were measured by univariate analysis. The intraoperative mean serum BNP level was compared with other predictors using the AUC, and was analyzed for its relationship with EAD by multivariate logistic regression. RESULTS A total of 31 patients (29.8%) developed EAD after LDLT. In all phases, the EAD group showed higher serum BNP levels than the non-EAD group. The serum BNP level at each phase was less accurate than the mean serum BNP level for EAD. The intraoperative mean serum BNP level showed higher predictive accuracy than the Child-Pugh-Turcotte, model for end-stage liver disease (MELD), and D-MELD (donor age × recipient MELD) scores (p<0.05 for all). After multivariate adjustment, intraoperative mean serum BNP level ≥100 pg/mL was identified as an independent risk factor for EAD, along with kidney disease and graft ischemic time. CONCLUSIONS During LDLT, the EAD group showed higher serum BNP levels than the non-EAD group. An intraoperative mean serum BNP level ≥100 pg/mL is independently associated with EAD after LDLT. PMID:27572618

  2. Elevated plasma levels of B-type natriuretic Peptide but not C-reactive protein are associated with higher red cell distribution width in patients with coronary artery disease.

    PubMed

    Fukuta, Hidekatsu; Ohte, Nobuyuki; Mukai, Seiji; Saeki, Tomoaki; Asada, Kaoru; Wakami, Kazuaki; Kimura, Genjiro

    2009-05-01

    Although higher red cell distribution width (RDW) has recently been reported to be associated with increased mortality independent of anemia in patients with heart failure and those with coronary artery disease (CAD), the mechanism underlying this association is unknown. We hypothesized that higher RDW may reflect neurohumoral activation and a chronic inflammatory state that each contribute to adverse clinical outcomes in these populations. We measured RDW and plasma levels of B-type natriuretic peptide (BNP) and high-sensitive C-reactive protein (hs-CRP) in 226 consecutive patients undergoing cardiac catheterization for CAD (age, 67 +/- 8 years; males, 77%; RDW, 45.8 +/- 3.3 fL; hemoglobin, 13.2 +/- 1.4 g/dL; BNP, median [interquartile range], 26.0 [9.0-58.4] pg/mL; hs-CRP, 679 [345-1920] ng/mL). Plasma BNP (r = 0.21, P < 0.01) but not hs-CRP (r = 0.04, P > 0.1) levels correlated with RDW. After adjustment for potential confounders including age, gender, body mass index, glomerular filtration rate, hemoglobin, and known hemodynamic determinants of BNP, including elevated left ventricular end-diastolic pressure and volume and slow left ventricular relaxation, RDW was independently predicted by BNP (r(2) = 0.058, P < 0.001). In conclusion, elevated BNP levels are independently associated with higher RDW in patients with CAD. Neurohumoral activation may be a mechanistic link between increased RDW and adverse clinical outcomes in this population. PMID:19506334

  3. Association of rs5888 SNP in the scavenger receptor class B type 1 gene and serum lipid levels

    PubMed Central

    2012-01-01

    Background Bai Ku Yao is a special subgroup of the Yao minority in China. The present study was undertaken to detect the association of rs5888 single nucleotide polymorphism (SNP) in the scavenger receptor class B type 1 (SCARB1) gene and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations. Methods A total of 598 subjects of Bai Ku Yao and 585 subjects of Han Chinese were randomly selected from our stratified randomized cluster samples. Genotypes of the SCARB1 rs5888 SNP were determined by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. Results The levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein (Apo) AI were lower but ApoB was higher in Bai Ku Yao than in Han (P < 0.05-0.001). The frequencies of C and T alleles were 78.3% and 21.7% in Bai Ku Yao, and 73.7% and 26.3% in Han (P < 0.01); respectively. The frequencies of CC, CT and TT genotypes were 60.0%, 36.6% and 3.4% in Bai Ku Yao, and 54.2%, 39.0% and 6.8% in Han (P < 0.01); respectively. The subjects with TT genotype in both ethnic groups had lower HDL-C and ApoAI levels than the subjects with CC or CT genotype (P < 0.05 for all). Subgroup analyses showed that the subjects with TT genotype in Bai Ku Yao had lower HDL-C and ApoAI levels in males than the subjects with CC or CT genotype (P < 0.05 for all), and the T allele carriers had higher TC, LDL-C and ApoB levels in females than the T allele noncarriers (P < 0.05 for all). The participants with TT genotype in Han also had a lower tendency of HDL-C and ApoAI levels in males than the participants with CC or CT genotype, but the difference did not reach statistically significant (P = 0.063 and P = 0.086; respectively). The association of serum HDL-C and ApoAI levels and genotypes was confirmed by

  4. B-type natriuretic peptide and high sensitive C-reactive protein predict 2-year all cause mortality in chest pain patients: a prospective observational study from Salta, Argentina

    PubMed Central

    2011-01-01

    Background Several mechanisms are involved in the pathophysiology of the Acute Coronary Syndrome (ACS). We have addressed whether B-type natriuretic peptide (BNP) and high-sensitive C-reactive protein (hsCRP) in admission samples may improve risk stratification in chest pain patients with suspected ACS. Methods We included 982 patients consecutively admitted with chest pain and suspected ACS at nine hospitals in Salta, Northern Argentina. Total and cardiac mortality were recorded during a 2-year follow up period. Patients were divided into quartiles according to BNP and hsCRP levels, respectively, and inter quartile differences in mortality were statistically evaluated applying univariate and multivariate analyses. Results 119 patients died, and the BNP and hsCRP levels were significantly higher among these patients than in survivors. In a multivariable Cox regression model for total death and cardiac death in all patients, the hazard ratio (HR) in the highest quartile (Q4) as compared to the lowest quartile (Q1) of BNP was 2.32 (95% confidence interval (CI), 1.24-4.35), p = 0.009 and 3.34 (95% CI, 1.26-8.85), p = 0.015, respectively. In the TnT positive patients (TnT > 0.01 ng/mL), the HR for total death and cardiac death in Q4 as compared to Q1 was 2.12 (95% CI, 1.07-4.18), p = 0.031 and 3.42 (95% CI, 1.13-10.32), p = 0.029, respectively. The HR for total death for hsCRP in Q4 as compared to Q1 was 1.97 (95% CI, 1.17-3.32), p = 0.011, but this biomarker did not predict cardiac death (p = 0.21). No prognostic impact of these two biomarkers was found in the TnT negative patients. Conclusion BNP and hsCRP may act as clinically useful biomarkers when obtained at admission in a population with suspected ACS. Trial Registration ClinicalTrials.gov Identifier: NCT01377402. PMID:21958326

  5. Prognostic impact of neutrophil gelatinase-associated lipocalin and B-type natriuretic in patients with ST-elevation myocardial infarction treated by primary PCI: a prospective observational cohort study

    PubMed Central

    Helanova, Katerina; Littnerova, Simona; Kubena, Petr; Ganovska, Eva; Pavlusova, Marie; Kubkova, Lenka; Jarkovsky, Jiri; Pavkova Goldbergova, Monika; Lipkova, Jolana; Gottwaldova, Jana; Kala, Petr; Toman, Ondrej; Dastych, Milan; Spinar, Jindrich; Parenica, Jiri

    2015-01-01

    Objectives Neutrophil gelatinase-associated lipocalin (NGAL) from a pathophysiological perspective connects various pathways that affect the prognosis after myocardial infarction. The objective was to evaluate the benefits of measuring NGAL for prognostic stratification in addition to the Thrombolysis in Myocardial Infarction (TIMI) score, and to compare it with the prognostic value of B-type natriuretic peptide (BNP). Design Prospective observational cohort study. Setting One university/tertiary centre. Participants A total of 673 patients with ST segment elevation myocardial infarction were treated by primary percutaneous coronary intervention. NGAL and BNP were assessed on hospital admission. Outcomes Primary outcome: 1-year mortality. Secondary outcomes: 1-year hospitalisation due to acute heart failure, unplanned revascularisation, reinfarction, stroke and combined end point of 1-year mortality and hospitalisation due to heart failure. Statistical methods Using the c-statistic, the ability of NGAL, BNP and TIMI score to predict 1-year mortality alone and in combination with readmission for heart failure was evaluated. The addition of the predictive value of biomarkers to the score was assessed by category free net reclassification improvement (cfNRI) and the integrated discrimination index (IDI). Results The NGAL level was significantly higher in non-survivors (67 vs 115 pg/mL; p<0.001). The area under the curve (AUC) values for mortality prediction for NGAL, BNP and TIMI score were 75.5, 78.7 and 74.4, respectively (all p<0.001) with optimal cut-off values of 84 pg/mL for NGAL and 150 pg/mL for BNP. The addition of NGAL and BNP to the TIMI score significantly improved risk stratification according to cfNRI and IDI. A BNP and the combination of the TIMI score with NGAL predicted the occurrence of the combined end point with an AUC of 80.6 or 82.2, respectively. NGAL alone is a simple tool to identify very high-risk patients. NGAL >110 pg/mL was

  6. [Diagnostic Ability of Natriuretic Peptides for Heart Failure According to eGFR Level: Comparison between Brain Natriuretic Peptide and Amino-Terminal Probrain Natriuretic Peptide].

    PubMed

    Arakawa, Kimika; Ando, Yukichi; Matsunaga, Sachiko; Nishiura, Akihiko

    2016-03-01

    Although the influence of reduced kidney function on natriuretic peptides (B-type natriuretic peptide [BNP] and amino terminal probrain natriuretic peptide [NT]) is clear, effect of kidney function on the difference of diagnostic ability for heart failure by these peptides is not obvious. The aim of this study was to examine the relationship between natriuretic peptide concentrations and echocardiographic findings according to eGFR level of the patients. In addition, we compared diagnostic ability of BNP with that of NT according to eGFR level. The eGFR levels were classified by based on CKD stage (≥ 60, 45-59, 30-44, 15-29, < 15 and on maintenance HD). Patients who underwent the measurements of BNP, NT and serum creatinine concentrations, as well as echocardiography between March and October in 2011 were enrolled (n = 1,297). The left ventricular mass index was greater in patients with eGFR < 60 than in those with eGFR ≥ 60, but EF (%) was not different among eGFR level (except eGFR30-44). The percentage of patients with heart failure in those with eGFR < 60 (16.0%) was more than eGFR ≥ 60 (5.8%). Median BNP and NT concentrations were elevated in association with decreasing eGFR level. Using receiver-operator characteristic (ROC) analysis, the area under the ROC curve for BNP and NT that stratified subjects with or without heart failure was not different among eGFR level. In conclusion, BNP and NT levels are elevated depend on decreasing eGFR level, BNP and NT are comparable in the accuracy for diagnosing heart failure at every eGFR level. The cut-off value of BNP and NT should be established according to the eGFR level. PMID:27363216

  7. How does serum brain natriuretic peptide level change under nasal continuous positive airway pressure in obstructive sleep apnea-hypopnea syndrome?

    PubMed Central

    Msaad, Sameh; Marrakchi, Rim; Grati, Malek; Gargouri, Rahma; Kammoun, Samy; Jammoussi, Kamel; Yangui, Ilhem

    2016-01-01

    Background Obstructive sleep apnea-hypopnea syndrome (OSAHS) is associated with cardiovascular morbidity and mortality, which can be improved by using continuous positive airway pressure (CPAP) therapy. However, the pathophysiological links between the two kinds of disease and the mechanism of the CPAP effect remain incompletely understood. We aimed to inquire into the myocardial involvement in this relationship. We suggested that serum brain natriuretic peptide (BNP) is sensitive enough to detect myocardial stress caused by OSAHS. Design and methods Sixty-four subjects without cardiovascular disease (21 controls, 24 normotensive OSAHS patients, and 19 hypertensive OSAHS patients) were analyzed for serum BNP at baseline and serially over 6 months. CPAP was applied to 23 patients with severe OSAHS. Results At baseline, the serum BNP levels were significantly higher (p=0.0001) in the OSAHS group (22.3±14.79 pg/ml) than in the control group (9.2±6.75 pg/ml). Increased serum BNP levels were significantly associated with mean transcutaneous oxygen saturation (SpO2) (p<0.0001), minimal SpO2 (p=0.002), oxygen desaturation index (p=0.001), and total sleep time spent with SpO2 lower than 90% (p=0.002). All patients with elevated BNP levels (≥37 pg/ml) had moderate or severe OSAHS (11/43 OSAHS patients). The more severe the OSAHS, the higher the BNP levels were. However, only the difference between severe and mild OSAHS was statistically significant (p=0.029). Hypertensive OSAHS patients had the highest baseline BNP levels (27.7±16.74 pg/ml). They were significantly higher (p=0.001) than in normotensive OSAHS patients (18±11.72 pg/ml) (p=0.039) and the controls (9.2±6.75 pg/ml). As compared with baseline, treatment with CPAP significantly decreased BNP levels in both hypertensive and normotensive OSAHS patients (respectively, from 36±16.10 to 29.7±14.29 pg/ml, p<0.001, and from 20±10.09 to 16±8.98 pg/ml, p<0.001). In contrast, the BNP levels slightly increased in

  8. Preliminary Development of a DNA Aptamer-Magnetic Bead Capture Electrochemiluminescence Sandwich Assay for Brain Natriuretic Peptide

    PubMed Central

    Bruno, John G.; Richarte, Alicia M.; Phillips, Taylor

    2014-01-01

    Fifty-two candidate DNA aptamer sequences were selected for binding to the cardiovascular biomarker B-type or brain natriuretic peptide (BNP). Candidate aptamers were screened to rank their relative affinities against BNP by an aptamer-based ELISA-like aptamer microplate assay (ELASA). The highest affinity aptamers from ELASA screening were also paired in all possible combinations and screened for electrochemiluminescence (ECL) assay potential in capture aptamer-magnetic bead and ruthenium trisbipyridine (Ru(bpy)32+)-reporter aptamer sandwich formats. The top ECL sandwich combinations utilized the same aptamer pair in either capture or reporting roles with nanogram to low picogram per mL levels of detection even in 50% human serum. ECL assay sensitivity and linearity even in 50% human serum suggest that the aptamer-based assay is at least comparable to other reported immunoassays for BNP. PMID:24764602

  9. 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.

  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. 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

  12. 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.

  13. 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

  14. Thirty years of the heart as an endocrine organ: physiological role and clinical utility of cardiac natriuretic hormones.

    PubMed

    Clerico, Aldo; Giannoni, Alberto; Vittorini, Simona; Passino, Claudio

    2011-07-01

    Thirty years ago, De Bold et al. (20) reported that atrial extracts contain some biologically active peptides, which promote a rapid and massive diuresis and natriuresis when injected in rats. It is now clear that the heart also exerts an endocrine function and in this way plays a key role in the regulation of cardiovascular and renal systems. The aim of this review is to discuss some recent insights and still-debated findings regarding the cardiac natriuretic hormones (CNHs) produced and secreted by cardiomyocytes (i.e., atrial natriuretic peptide and B-type natriuretic peptide). The functional status of the CNH system depends not only on the production/secretion of CNHs by cardiomyocytes but also on both the peripheral activation of circulating inactive precursor of natriuretic hormones and the transduction of the hormone signal by specific receptors. In this review, we will discuss the data supporting the hypothesis that the production and secretion of CNHs is the result of a complex integration among mechanical, chemical, hemodynamic, humoral, ischemic, and inflammatory inputs. The cross talk among endocrine function, adipose tissue, and sex steroid hormones will be discussed more in detail, considering the clinically relevant relationships linking together cardiovascular risk, sex, and body fat development and distribution. Finally, we will review the pathophysiological role and the clinical relevance of both peripheral maturation of the precursor of B-type natriuretic peptides and hormone signal transduction.

  15. 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.

  16. 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

  17. 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.

  18. Natriuretic Peptides in Kawasaki Disease: the Myocardial Perspective

    PubMed Central

    Dahdah, Nagib; Fournier, Anne

    2013-01-01

    Making a diagnosis of Kawasaki disease with certainty may be challenging, especially since the recognition of cases with incomplete diagnostic criteria and its consequences. In order to build the diagnostic case in daily practice, clinicians rely on clinical criteria established over four decades ago, aided by non specific laboratory tests, and above all inspired by experience. We have recently studied the diagnostic value of N-terminal pro B-type natriuretic peptide to improve the diagnostic certainty of cases with complete or incomplete clinical criteria. Our working hypothesis was based on the fact that myocarditis is present in nearly all Kawasaki disease patients supported by histology data. In this paper, we review these facts and the myocardial perspective from the diagnostic and the mechanistic standpoints. PMID:26835665

  19. 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.

  20. 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.

  1. 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

  2. Atrial natriuretic factor during hypoxia and mild exercise.

    PubMed

    Story, D A; Miller, B R; Shield, C M; Bowes, G

    1991-04-01

    The effect of hypoxia on plasma atrial natriuretic factor (ANF), plasma renin activity (PRA), and plasma aldosterone concentration (PAC) was evaluated during 2 h of treadmill exercise at 2 km/h, 0 grade at sea level. Six male subjects exercised on 2 separate days during normoxia (21% O2) and hypoxia (13.3 +/- 0.3% O2). No significant changes in ANF or PRA occurred during either normoxic or hypoxic exercise. However, PAC fell significantly during normoxic exercise (17.5 +/- 3.6 vs. 12.7 +/- 2.6 ng/dl, p less than 0.05) but not during hypoxic exercise. Serum potassium concentration fell during hypoxic exercise (5.0 +/- 0.1 vs. 4.4 +/- 0.1 mmol/l, p less than 0.05) along with bicarbonate (27.8 +/- 0.7 vs. 25.8 +/- 0.6 mmol/l, p less than 0.01). Between normoxic and hypoxic studies there was a significantly higher heart rate during hypoxic exercise (78 +/- 5 vs. 90 +/- 6 b/min, p less than 0.01). The major conclusion of this study is that hypoxia resulting in arterial oxygen saturations of 81 +/- 0.7% does not affect plasma atrial natriuretic factor levels during mild exercise in normal male subjects.

  3. Dissecting disks around B-type protostars

    NASA Astrophysics Data System (ADS)

    Sanchez-Monge, Alvaro; Cesaroni, Riccardo; Beltran, Maite; Kumar, M. S. Nanda; Stanke, Thomas; Zinnecker, Hans; Etoka, Sandra; Galli, Daniele; Hummel, Christian A.; Moscadelli, Luca; Preibisch, Thomas; Ratzka, Thorsten; van der Tak, Floris F. S.; Vig, Sarita; Walmsley, C. Malcolm; Wang, Kuo-Song

    2013-07-01

    Recent theoretical models indicate that OB-type stars could form through disk-mediated accretion, like their low mass counterparts. However, on the observational side, circumstellar disks appear still elusive, especially around the most massive (proto)stars. As for early B-type (proto)stars, an ever growing number of disk candidates has been proposed, but only very few of these present evidence for Keplerian rotation. The advent of ALMA provides us with the necessary sensitivity and angular resolution to assess the existence of such disks and possibly establish their rotation curves. With this in mind, we have performed ALMA observations with the highest possible resolution (~0.4") at 350 GHz to search for circumstellar disks in a couple of presumably massive young stellar objects with luminosities of ~10000 Lsun and associated with bipolar nebulosities suggestive of the presence of disk/outflow systems. By observing simultaneously core and jet tracers, we could reveal molecular cores with velocity gradients perpendicular to the corresponding jets. In at least one case (G35.20-0.74 N), the core structure appears resolved and the velocity field can be fitted with an almost edge-on Keplerian disk rotating about a central mass of 18 Msun. This finding is consistent with the results of a recent study of the CO first overtone bandhead emission at 2.3mum towards G35.20-0.74 N. The disk radius and mass are >2500 au and 3 Msun. To reconcile the observed bolometric luminosity (3x10^4 Lsun) with the estimated stellar mass of 18 Msun, we propose that the latter is the total mass of a binary system.

  4. Utility of point-of-care testing of natriuretic peptides (brain natriuretic peptide and n-terminal pro-brain natriuretic peptide) in the emergency department.

    PubMed

    Nayer, Jamshed; Aggarwal, Praveen; Galwankar, Sagar

    2014-07-01

    Rapid and accurate diagnosis of a patient with an acute disease is a challenge for emergency physicians. Natriuretic peptides have emerged as important tools for diagnosis, risk stratification and therapeutic decision making for some categories of emergency patients. Brain natriuretic peptide (BNP) is a member of a four natriuretic peptides family that shares a common 17-peptide ring structure. Atrial natriuretic peptide, C-natriuretic peptide (CNP), and D-type natriuretic peptide are the other natriuretic peptide, which share the same common 17-peptide ring structure. The N-terminal fragment of pro-BNP, N-terminal pro-brain natriuretic peptide (NT-proBNP) consists of 76 amino acids, which is biologically inert, while the active component BNP contains 32 amino acids. BNP and NT-proBNP are secreted in the plasma in equimolar quantities and are frequently used in the diagnosis of congestive heart failure, and distinguishing between patients with dyspnea of cardiac or pulmonary origin. Both natriuretic peptides have also been evaluated for use in the assessment and management of several other conditions including sepsis, cirrhosis of liver and renal failure. However, one should remember that the values of natriuretic peptides are affected by age and weight of the patients, and presence of several comorbidities such as chronic renal failure, type 2 diabetes mellitus, anemia, pulmonary embolism, and acute coronary syndrome. Values of these peptides also vary depending on the type of test used. The performance characteristics of these natriuretic peptides vary depending on the patients on whom they are used. Therefore determination of reference values for these peptides represents a challenge.

  5. Systemic inflammatory response syndrome following burns is mediated by brain natriuretic peptide/natriuretic peptide A receptor-induced shock factor 1 signaling pathway.

    PubMed

    Xu, Yang-Cheng; Luo, Cheng-Qun; Li, Xiong

    2016-10-01

    The aim of this study was to determine whether systemic inflammatory response syndrome (SIRS) in burn patients is mediated by the brain natriuretic peptide (BNP)/natriuretic peptide A receptor (NPRA)-induced heat shock factor 1 (HSF-1) signalling pathway. Mononuclear cells (MNCs) that were isolated from patients with burn injuries and SIRS mouse models and a RAW264.7 cell line were treated with normal serum or serum obtained from animals with burn injuries. In parallel, small hairpin RNAs (shRNAs) against BNP or NPRA were transfected in both cell types. Western blotting (WB) and enzyme-linked immunosorbent assay (ELISA) were used to detect protein expression and inflammatory factor levels, respectively. We found that interleukin (IL)-12, tumour necrosis factor (TNF)-α, C-reactive protein (CRP), and BNP levels were increased and IL-10 levels were decreased in the plasma and MNCs in vivo in the animal model of SIRS. Additionally, NPRA was upregulated, whereas HSF-1 was downregulated in monocytes in vivo. Treatment of RAW264.7 cells with burn serum or BNP induced IL-12, TNF-α, and CRP secretion as well as HSF-1 expression. Finally, silencing BNP with shRNA interrupted the effect of burn serum on RAW264.7 cells, and silencing NPRA blocked burn serum- and BNP-mediated changes in RAW264.7 cells. These results suggest that the interaction of NPRA with BNP secreted from circulatory MNCs as well as mononuclear macrophages leads to inflammation via HSF-1 during SIRS development following serious burn injury.

  6. Influence of natriuretic peptide receptor-1 on survival and cardiac hypertrophy during development

    PubMed Central

    Scott, Nicola J.A.; Ellmers, Leigh. J.; Lainchbury, John G.; Maeda, Nobuyo; Smithies, Oliver; Richards, A. Mark; Cameron, Vicky A.

    2010-01-01

    The heart adapts to an increased workload through the activation of a hypertrophic response within the cardiac ventricles. This response is characterized by both an increase in the size of the individual cardiomyocytes and an induction of a panel of genes normally expressed in the embryonic and neonatal ventricle, such as atrial natriuretic peptide (ANP). ANP and brain natriuretic peptide (BNP) exert their biological actions through activation of the natriuretic peptide receptor-1 (Npr1). The current study examined mice lacking Npr1 (Npr1−/−) activity and investigated the effects of the absence of Npr1 signaling during cardiac development on embryo viability, cardiac structure and gene and protein expression. Npr1−/−embryos were collected at embryonic day (ED) 12.5, 15.5 and neonatal day 1 (ND 1). Npr1−/−embryos occurred at the expected Mendelian frequency at ED 12.5, but knockout numbers were significantly decreased at ED 15.5 and ND 1. There was no indication of cardiac structural abnormalities in surviving embryos. However, Npr1−/−embryos exhibited cardiac enlargement (without fibrosis) from ED 15.5 as well as significantly increased ANP mRNA and protein expression compared to wild-type (WT) mice, but no concomitant increase in expression of the hypertrophy-related transcription factors, Mef2A, Mef2C, GATA-4, GATA-6 or serum response factor (SRF). However, there was a significant decrease in Connexin-43 (Cx43) gene and protein expression at mid-gestation in Npr1−/−embryos. Our findings suggest that the mechanism by which natriuretic peptide signaling influences cardiac development in Npr1−/− mice is distinct from that seen during the development of pathological cardiac hypertrophy and fibrosis. The decreased viability of Npr1−/−embryos may result from a combination of cardiomegaly and dysregulated Cx43 protein affecting cardiac contractility. PMID:19782130

  7. ED 05-4 NATRIURETIC PEPTIDES, METABOLIC SYNDROME AND HYPERTENSION: AN INTEGRATED VIEW.

    PubMed

    Sarzani, Riccardo

    2016-09-01

    Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) are the cardiac natriuretic peptides (NP), true "cardiometabolic" hormones well known for their renal, endocrine and cardiovascular activities leading to reduced sodium reabsorption and arterial blood pressure. These effects are mainly mediated by the second messenger cGMP that also stimulates lipolysis, mitochondriogenesis and a thermogenic program with potency similar to catecholamines. Two distinct NP receptors modulate the final response to cardiac NP: the cGMP-signaling receptor NPRA and the clearance receptor NPRC. The cellular and systemic effects of NP largely depend upon the ratio of the clearance receptor NPRC to the signaling receptor NPRA, both abundantly expressed in human adipose tissue and adipocytes. Indeed, most of the available data indicate that the total NPRC expression in the body is the main negative modulator of the circulating NP levels and, at cellular level, NPRC is a main silencer of their biological effects. NP are not only 'cleared' from circulation by NPRC, but they are also degraded very quickly by neutral endopeptidase (NEP) and both are increased in obesity. Starving sharply decreases NPRC expression in white and brown adipose tissue and a low-calorie diet in obese hypertensive patients strongly potentiates the clinical and biological effects of infused ANP. Hypocaloric diet also enhances ANP-induced lipolysis in humans, whereas obesity is associated with lower circulating levels of NP. Many studies have linked the genes of NP and their receprtros to hypertension and many population studies have also linked reduced NP levels to obesity and metabolic syndrome. Insulin/glucose are the main factors in adipocytes hypertrophy in many conditions characterized by insulin resistance such as metabolic syndrome. Insulin attenuate lipolysis in adipocytes by inducing NPRC expression, linking the eating pattern to reduced NP activities both on adipose tissue and likely in the

  8. Association of brain-type natriuretic protein and cardiac troponin I with incipient cardiovascular disease in chimpanzees (Pan troglodytes).

    PubMed

    Ely, John J; Zavaskis, Tony; Lammey, Michael L; Sleeper, Meg M; Lee, D Rick

    2011-04-01

    Cardiovascular disease (CVD) is the primary cause of morbidity and mortality in chimpanzees, but its etiology and clinical presentations remain poorly understood. The disease in chimpanzees differs sufficiently from that in humans that simple extrapolation from human findings are inadequate to guide clinical diagnoses. Nevertheless, the burden of disease posed by CVD made it important to attempt to identify specific chimpanzees at risk of developing CVD to allow clinical intervention prior to clinical presentation of advanced disease. We screened 4 CVD biomarkers used in human and veterinary medicine to identify markers with prognostic value in chimpanzees. Biomarkers included complete lipid panel, C-reactive protein, brain-type natriuretic protein, and cardiac troponin I. Serum levels of brain-type natriuretic protein differed between chimpanzees with CVD and heart-healthy controls. Cardiac troponin I gave mixed results. C-reactive protein and lipid panel values were not informative for cardiovascular disease, although total cholesterol, LDL-cholesterol, and triglycerides increased significantly with decade of life. Values of braintype natriuretic protein exceeding 163 mg/mL had a specificity of 90.5% for CVD, whereas levels of cardiac troponin I above the threshold of detection (0.20 ng/mL) appeared to be clinically relevant. More extensive clinical studies are recommended to validate these specific values. We conclude that brain-type natriuretic protein and possibly cardiac troponin I are useful diagnostic biomarkers for incipient CVD processes in chimpanzees. PMID:21535928

  9. Association of Brain-Type Natriuretic Protein and Cardiac Troponin I with Incipient Cardiovascular Disease in Chimpanzees (Pan troglodytes)

    PubMed Central

    Ely, John J; Zavaskis, Tony; Lammey, Michael L; Sleeper, Meg M; Lee, D Rick

    2011-01-01

    Cardiovascular disease (CVD) is the primary cause of morbidity and mortality in chimpanzees, but its etiology and clinical presentations remain poorly understood. The disease in chimpanzees differs sufficiently from that in humans that simple extrapolation from human findings are inadequate to guide clinical diagnoses. Nevertheless, the burden of disease posed by CVD made it important to attempt to identify specific chimpanzees at risk of developing CVD to allow clinical intervention prior to clinical presentation of advanced disease. We screened 4 CVD biomarkers used in human and veterinary medicine to identify markers with prognostic value in chimpanzees. Biomarkers included complete lipid panel, C-reactive protein, brain-type natriuretic protein, and cardiac troponin I. Serum levels of brain-type natriuretic protein differed between chimpanzees with CVD and heart-healthy controls. Cardiac troponin I gave mixed results. C-reactive protein and lipid panel values were not informative for cardiovascular disease, although total cholesterol, LDL-cholesterol, and triglycerides increased significantly with decade of life. Values of brain-type natriuretic protein exceeding 163 mg/mL had a specificity of 90.5% for CVD, whereas levels of cardiac troponin I above the threshold of detection (0.20 ng/mL) appeared to be clinically relevant. More extensive clinical studies are recommended to validate these specific values. We conclude that brain-type natriuretic protein and possibly cardiac troponin I are useful diagnostic biomarkers for incipient CVD processes in chimpanzees. PMID:21535928

  10. Natriuretic Peptides as Predictors of Atrial Fibrillation Recurrences Following Electrical Cardioversion.

    PubMed

    Zografos, Theodoros A; Katritsis, Demosthenes G

    2013-11-01

    Electrical cardioversion (ECV) can be effective in restoring sinus rhythm (SR) in the majority of patients with atrial fibrillation (AF). Several factors that predispose to AF recurrences, such as age, AF duration and left atrial size have been used to guide a decision for cardioversion, but increasing evidence suggests that they may be rather poor markers of left atrial structural remodeling that determines the long-term success of a rhythm control strategy. In this context, the use of easily obtainable biomarkers, such as the levels of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), to predict AF recurrences may be preferable. Since ANP production is associated with the extent of functional atrial myocardium, and both ANP and BNP reflect atrial pressure and mechanical stretching, these peptides are good candidate biomarkers to assess predisposition to AF recurrences. In this review we focus on the pathophysiological mechanisms and the available clinical evidence regarding the prediction of AF recurrences following successful ECV from pre-procedural ANP and BNP levels.

  11. Natriuretic Peptides as Predictors of Atrial Fibrillation Recurrences Following Electrical Cardioversion

    PubMed Central

    Zografos, Theodoros A; Katritsis, Demosthenes G

    2013-01-01

    Electrical cardioversion (ECV) can be effective in restoring sinus rhythm (SR) in the majority of patients with atrial fibrillation (AF). Several factors that predispose to AF recurrences, such as age, AF duration and left atrial size have been used to guide a decision for cardioversion, but increasing evidence suggests that they may be rather poor markers of left atrial structural remodeling that determines the long-term success of a rhythm control strategy. In this context, the use of easily obtainable biomarkers, such as the levels of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), to predict AF recurrences may be preferable. Since ANP production is associated with the extent of functional atrial myocardium, and both ANP and BNP reflect atrial pressure and mechanical stretching, these peptides are good candidate biomarkers to assess predisposition to AF recurrences. In this review we focus on the pathophysiological mechanisms and the available clinical evidence regarding the prediction of AF recurrences following successful ECV from pre-procedural ANP and BNP levels. PMID:26835050

  12. [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

  13. Biomarkers Beyond the Natriuretic Peptides for Chronic Heart Failure: Galectin-3 and Soluble ST2

    PubMed Central

    2012-01-01

    B-type natriuretic peptide (BNP) and NT-proBNP are widely used plasma biomarkers for the diagnosis of acute decompensated heart failure and prognosis for future cardiac disease. The clinical performance of these tests for management of chronic heart failure is somewhat limited by the markers’ high biological variation. Biomarkers such as galectin-3 and soluble ST2 that reflect ongoing remodeling via cardiac fibrosis of the heart may provide complementary information to the natriuretic peptides in the management of chronic heart failure with regards to risk stratification for future adverse cardiac events (death, myocardial infarction, and need for heart transplantation). However, implementation of these biomarkers into routine clinical practice requires documentation that these tests will enable therapeutic decisions that can be made to improve clinical outcomes, and the availability of commercial assays. This report will discuss the need for novel heart failure biomarkers, ideal characteristics of assays, and review and compare the clinical performance of assays for galectin-3 and sST2 for chronic heart failure disease management.

  14. 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

  15. Atrial natriuretic factor and body water distribution.

    PubMed

    Vidal, N A; Arranz, C T; Mones Sias, M C; Herrmann, A P; Martinez Seeber, A

    1987-11-01

    In the rat, the effects of an atrial natriuretic factor (ANF) (Rat, 8-33 Peninsula Lab) on body water distribution have been evaluated. The ANF administration to nephrectomized animals produced a decrease in plasma volume and a slight increase in haematocrit and in plasma albumin concentration. No modifications were observed in total and intracellular water. The fluid efflux from the capillaries appeared to be located in the interstitial space. These results suggest that ANF could regulate plasma volume and systemic blood pressure, concurrently with its other known effects.

  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. Identification of Magnetite in B-type Asteroids

    NASA Astrophysics Data System (ADS)

    Yang, Bin; Jewitt, David

    2010-09-01

    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 μm. The 1 μm band can be matched in position and shape using magnetite (Fe3O4), 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 μm region reveal an absorption feature centered at 2.9 μm, 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.

  18. 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.

  19. Usefulness of natriuretic peptide for the diagnosis of Kawasaki disease: a systematic review and meta-analysis

    PubMed Central

    Lin, Kuan-Ho; Chang, Shy-Shin; Yu, Chin-Wei; Lin, Shen-Che; Liu, Shu-Chun; Chao, Hsiao-yun; Wu, Jiunn-Yih; Lee, Chien-Chang

    2015-01-01

    Objective To examine the diagnostic value of serum B-type natriuretic peptide (BNP) in acute Kawasaki disease (KD). Design Systematic review and meta-analysis. Data sources A systematic literature search strategy was designed and carried out using MEDLINE, EMBASE and the Cochrane Library from inception to December 2013. We also performed manual screening of the bibliographies of primary studies and review articles, and contacted authors for additional data. Study eligibility criteria We included all BNP and NT-pro (N-terminal prohormone) BNP assay studies that compared paediatric patients with KD to patients with febrile illness unrelated to KD. We excluded case reports, case series, review articles, editorials, congress abstracts, clinical guidelines and all studies that compared healthy controls. Primary and secondary outcome measures The performance characteristics of BNP were summarised using forest plots, hierarchical summary receiver operating characteristic (ROC) curves and bivariate random effects models. Results We found six eligible studies including 279 cases of patients with KD and 203 febrile controls. Six studies examined NT-proBNP and one examined BNP. In general, NT-proBNP is a specific and moderately sensitive test for identifying KD. The pooled sensitivity was 0.89 (95% CI 0.78 to 0.95) and the pooled specificity was 0.72 (95% CI 0.58 to 0.82). The area under the summary ROC curve was 0.87 (95% CI 0.83 to 0.89). The positive likelihood ratio (LR+ 3.20, 95% CI 2.10 to 4.80) was sufficiently high to be qualified as a rule-in diagnostic tool in the context of high pre-test probability and compatible clinical symptoms. A high degree of heterogeneity was found using the Cochran Q statistic. Conclusions Current evidence suggests that NT-proBNP may be used as a diagnostic tool for KD. NT-proBNP has high diagnostic value for identifying KD in patients with protracted undifferentiated febrile illness. Prospective large cohort studies are needed to help

  20. Differential gene expression of the three natriuretic peptides and natriuretic peptide receptor subtypes in human liver.

    PubMed Central

    Vollmar, A M; Paumgartner, G; Gerbes, A L

    1997-01-01

    BACKGROUND: Various effects of atrial natriuretic peptide (ANP) on the liver have been observed. However, there is limited information about the types of receptors for natriuretic peptides expressed by the human liver. AIM: To investigate gene expression of the three NP receptor types (NPR) as well as of the NP in human liver. METHODS: Presence of mRNA coding for all three NPR and for ANP, brain and C-type natriuretic peptide (BNP, CNP) was investigated by reverse transcription-polymerase chain reaction (RT-PCR). Human liver tissues and hepatocellular carcinoma tissues were examined. RESULTS: Specific PCR products for all three NPR, namely NPR-A, B, and C, could be detected. Moreover, ANP and CNP, but not BNP mRNA was detectable. The concentration of ANP transcripts was up to fivefold higher in hepatocellular carcinoma compared with non-tumorous liver tissue of the same subjects. No difference in the expression of NP receptors relative to GAPDH mRNA of tumorous and non-tumorous tissue was observed except of slightly increased NPR-A transcripts. CONCLUSION: These data show that NPR transcripts are coexpressed with ANP and CNP mRNA in the human liver. This provides evidence for a local NP system in the human liver. Images PMID:9155593

  1. Inverse association of long-acting natriuretic peptide with metabolic syndrome in congestive heart failure patients

    PubMed Central

    2013-01-01

    Aims Long-acting natriuretic peptide (LANP) is one of the peptide hormones in atrial natriuretic peptide (ANP) pro-hormone. Low levels of natriuretic peptide may lead to reduced lipolysis and excessive weight gain in obese patients. The aim of this study was to investigate the relationship between fasting serum LANP level and the metabolic syndrome (MetS) among congestive heart failure (CHF) patients. Methods Fasting blood samples were obtained from 186 patients with normal renal function in cardiac clinic outpatients. CHF defined by the American College of Cardiology Foundation and the American Heart Association 2005 Guidelines. MetS and its components were defined using diagnostic criteria from the International Diabetes Federation. Results Ninety-eight patients (52.7%) had CHF. There was a tendency of increased fasting LANP levels as the NYHA CHF functional classes increased (p = 0.002). Forty-six of the CHF patients (46.9%) had MetS. Fasting LANP level negatively correlated with MetS among CHF patients (p < 0.001). Univariate linear regression analysis showed that BUN (p = 0.026) positively correlated with fasting serum LANP levels, while body weight (p = 0.009), BMI (p = 0.004), homeostasis model assessment of insulin resistance (HOMA-IR; p = 0.024) and HOMA-β (p = 0.001) negatively correlated with fasting serum LANP levels among the CHF patients. Multivariate forward stepwise linear regression analysis of the significant variables showed that the HOMA-β (R2 change = 0.292, p < 0.001) and HOMA-IR (R2 change = 0.081, p = 0.019) were independent predictors of fasting serum LANP levels in CHF patients. Conclusions LANP level is significantly reduced in CHF patients affected by MetS. HOMA-β and HOMA-IR were independent predictors of serum LANP levels in CHF patients. PMID:23566312

  2. 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

  3. 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

  4. SP 04-1 THE ROLE OF NATRIURETIC PEPTIDES IN THE PATHOGENESIS OF CARDIOVASCULAR DISEASES.

    PubMed

    Kobalava, Zhanna

    2016-09-01

    The burden of cardiovascular diseases (CVD) in general and heart failure (HF) in particular continues to increase worldwide. CVD are major contributors to death and morbidity and recognized as important drivers of healthcare expenditure. Chronic overactivity of the renin-angiotensin-aldosterone system (RAAS) plays a key role in human hypertension and HF pathophysiology. RAAS is fundamental in the overall regulation of cardiovascular homeostasis through the actions of hormones, which regulate vascular tone, and specifically blood pressure through vasoconstriction and renal sodium and water retention. Drugs inhibiting key components of the RAAS have become a cornerstone of contemporary cardiovascular drug therapy. Nowadays there is a high priority for the development of innovative therapeutic agents that better control blood pressure, have a therapeutic potential in HF and enhance current therapies for CVD. The enhancement of the biological activities of the natriuretic peptides (NP) via inhibition of their degradation is one of the novel strategies.Natriuretic peptide system includes primarily three well-characterized peptides with structural similarity: atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). These three peptides are involved in the maintenance of cardio-renal homeostasis and all have cardio-renal protective properties. Atrial natriuretic peptide and BNP are synthetized mainly by the cardiomyocytes in response to cardiac stretch, whereas CNP is mainly produced by endothelial cells in response to cytokines and endothelium-dependent agonists. B-type natriuretic peptide is also produced by cardiofibroblasts where it elicits its antifibrotic actions in the heart. All NP function via the second messenger cGMP. All three peptides are cleared by the clearance receptor (NPR-C), not linked to a guanylate cyclase. The NP are also cleared from the circulation via enzymatic degradation by neutral endopeptidase

  5. Atrial natriuretic peptide: water and electrolyte homeostasis.

    PubMed

    Kenyon, C J; Jardine, A G

    1989-08-01

    In the few years since its identification, a clear role for ANP in the regulation of water and electrolyte balance has emerged (Figure 3). The peptide is released in response to blood volume expansion, both acutely and gradually during changes in dietary sodium intake. Similarly, plasma levels are elevated in pathophysiological conditions such as cardiac and renal failure. It has become apparent that ANP has natriuretic, diuretic and vasorelaxant properties. Many of the original studies employed what we now know to be pharmacological doses of the peptide. However, recent reports have confirmed that small, sustained elevations in plasma ANP within or marginally above the 'normal' physiological range produce similar effects. A number of recent studies have tried to specifically address the physiological relevance of ANP. Although undoubtedly release by atrial distension and effective when infused to similar concentrations, atrial distension also has other effects via neural pathways. Thus, the demonstration that excretion of saline is impaired by atrial appendectomy (Benjamin et al, 1988) does not imply that this is only due to the absence of an atrial hormone. Goetz et al (1986) demonstrated that in the denervated heart, although ANP is still released, the excretion of a saline load is impaired. Similarly, in man, Richards et al (1988a) needed to infuse ANP to much higher plasma levels than those achieved by a saline load in order to reproduce the natriuresis. Although these experiments can be criticized, they confirm that ANP is not the sole mechanism for excreting a volume load, or for the natriuresis following atrial distension, but that these effects are likely to reflect the balance between ANP, AVP, the renin-angiotensin and autonomic nervous systems. In rats immunized against ANP (Greenwald et al, 1988), although the ability to excrete an acute saline load was impaired, long-term sodium balance was normal, suggesting that the rats were able to compensate for

  6. Diurnal gene expression of lipolytic natriuretic peptide receptors in white adipose tissue.

    PubMed

    Smith, Julie; Fahrenkrug, Jan; Jørgensen, Henrik L; Christoffersen, Christina; Goetze, Jens P

    2015-12-01

    Disruption of the circadian rhythm can lead to obesity and cardiovascular disease. In white adipose tissue, activation of the natriuretic peptide receptors (NPRs) stimulates lipolysis. We have previously shown that natriuretic peptides are expressed in a circadian manner in the heart, but the temporal expression profile of their cognate receptors has not been examined in white adipose tissue. We therefore collected peri-renal white adipose tissue and serum from WT mice. Tissue mRNA contents of NPRs - NPR-A and NPR-C, the clock genes Per1 and Bmal1, and transcripts involved in lipid metabolism were quantified at 4-h intervals: in the diurnal study, mice were exposed to a period of 12 h light followed by 12 h darkness (n=52). In the circadian study, mice were kept in darkness for 24 h (n=47). Concomitant serum concentrations of free fatty acids, glycerol, triglycerides (TGs), and insulin were measured. Per1 and Bmal1 mRNA contents showed reciprocal circadian profiles (P<0.0001). NPR-A mRNA contents followed a temporal pattern (P=0.01), peaking in the dark (active) period. In contrast, NPR-C mRNA was expressed in an antiphase manner with nadir in the active period (P=0.007). TG concentrations in serum peaked in the active dark period (P=0.003). In conclusion, NPR-A and NPR-C gene expression is associated with the expression of clock genes in white adipose tissue. The reciprocal expression may thus contribute to regulate lipolysis and energy homeostasis in a diurnal manner.

  7. Spectroscopy of B-Type Asteroids: Subgroups and Meteorite Analogs

    NASA Astrophysics Data System (ADS)

    Clark, Beth Ellen; Ziffer, J.; Nesvorny, D.; Campins, H.; Rivkin, A.; Hiroi, T.; Barucci, M. A.; Binzel, R.; Fornasier, S.; DeMeo, F.; Ockert-Bell, M.

    2009-09-01

    B-type asteroids have a negative slope from 0.5 to 1.1 microns and beyond. What causes this? Visible to near-infrared reflectance spectra (0.4 to 2.5 microns) are assembled for 22 B-type asteroids. The spectra fall naturally into three groups: 1) those with negative (blue) spectral shapes like 2 Pallas; 2) those with concave curve shapes like 24 Themis; and 3) everything else. The asteroid spectra are compared with mineral and meteorite spectra from the RELAB library of 15,000 samples, in a least-squares search for particulate analogs, constrained by spectral brightness. The Pallas group meteorite matches show a trend of "dry” analogs, such as CV, CO, and CK-meteorites. The Themis group meteorite matches show a trend of "wet” or "previously wet” analogs, such as CI, CM, CR, and CI- or CM-Unusual meteorites. Allowing for reasonable uncertainties in the spectral matches, we find no need to invoke mineralogies that do not exist in the meteorite collection to explain B-type spectra. Our Themis group results are as expected, and are consistent with previous work, but our Pallas group results are new, surprising, problematic, and in conflict with previous work.

  8. 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

  9. 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

  10. 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.

  11. Amino-terminal fragment of C-type natriuretic peptide precursor and C-type natriuretic peptide do not correlate in patients with Chagas disease: role for neutral endopeptidase.

    PubMed

    Wang, Yong; Moreira, Maria da Consolação V; Heringer-Walther, Silvia; Schultheiss, Heinz-Peter; Siems, Wolf-Eberhard; Wessel, Niels; Walther, Thomas

    2010-01-01

    Atrial and B-type natriuretic peptides (ANP and BNP), but not C-type natriuretic peptide (CNP), have been identified to be diagnostic and prognostic markers in Chagas disease (CD). Although ANP and BNP excessively rise in patients with CD, increase in CNP is just minor. Our study aimed to investigate the mechanisms leading to CNP insensitivity to heart failure (HF) stimuli. Amino-terminal fragment of CNP precursor (NT-proCNP) and activity of neutral endopeptidase (NEP) were quantified to monitor CNP generation and degradation, respectively. Blood samples were collected from patients with CD and control healthy subjects. NT-proCNP concentrations were significantly lower in patients with CD without systolic dysfunction compared with healthy subjects. Despite a trend toward increase with rising heart failure clinical severity, it was significantly correlated with left ventricular ejection fraction and other echocardiographic parameters. As shown for CNP before, NT-proCNP could not predict mortality and heart transplant. Importantly, it had no statistical correlation with CNP. Additionally, NEP activity was significantly increased in New York Heart Association III and IV patients with HF but was positively correlated with CNP concentration. Our data demonstrates that generation of CNP is not enhanced under HF condition like CD. Thus, CNP rise by severe HF is caused by its less degradation that is independent of NEP activity.

  12. 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.

  13. 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.

  14. Biochemistry and physiology of the natriuretic peptide receptor guanylyl cyclases.

    PubMed

    Tremblay, Johanne; Desjardins, Richard; Hum, David; Gutkowska, Jolanta; Hamet, Pavel

    2002-01-01

    Guanylyl cyclases (GC) exist as soluble and particulate, membrane-associated enzymes which catalyse the conversion of GTP to cGMP, an intracellular signalling molecule. Several membrane forms of the enzyme have been identified up to now. Some of them serve as receptors for the natriuretic peptides, a family of peptides which includes atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP), three peptides known to play important roles in renal and cardiovascular physiology. These are transmembrane proteins composed of a single transmembrane domain, a variable extracellular natriuretic peptide-binding domain, and a more conserved intracellular kinase homology domain (KHD) and catalytic domain. GC-A, the receptor for ANP and BNP, also named natriuretic peptide receptor-A or -1 (NPR-A or NPR- 1), has been studied widely. Its mode of activation by peptide ligands and mechanisms of regulation serve as prototypes for understanding the function of other particulate GC. Activation of this enzyme by its ligand is a complex process requiring oligomerization, ligand binding, KHD phosphorylation and ATP binding. Gene knockout and genetic segregation studies have provided strong evidence for the importance of GC-A in the regulation of blood pressure and heart and renal functions. GC-B is the main receptor for CNP, the latter having a more paracrine role at the vascular and venous levels. The structure and regulation of GC-B is similar to that of GC-A. This chapter reviews the structure and roles of GC-A and GC-B in blood pressure regulation and cardiac and renal pathophysiology. PMID:11952095

  15. Measurement of the pro-hormone of brain type natriuretic peptide (proBNP): methodological considerations and pathophysiological relevance.

    PubMed

    Clerico, Aldo; Vittorini, Simona; Passino, Claudio

    2011-08-26

    Recent studies demonstrated that large amounts of the pro-hormone peptide of brain natriuretic peptide (proBNP) can be detected in plasma of healthy subjects and in particular of patients with heart failure. As a result, a great part of B-type natriuretic peptides measured in patients with cardio-vascular disease may be devoid of biological activity. These findings stimulated the set up of specific immunoassay methods for the measurement of the intact proBNP peptide. The aim of this review article is to discuss the methodological characteristics and the possible clinical relevance of specific immunoassay methods for the measurement of the proBNP peptide. From an analytical point of view, a fully automated immunoassay of proBNP has some theoretical advantages (e.g., a more stable molecule with higher molecular weight than the derived peptides) compared to the active hormone BNP. Recent studies supported the concept that the precursor proBNP might be actually considered a circulating prohormone, which can be cleaved by specific plasma proteases in BNP, the active hormone, and NT-proBNP, an inactive peptide. The peripheral processing of circulating proBNP could likely be submitted to regulatory rules, which might be impaired in patients with heart failure, opening new perspectives in the treatment of heart failure (e.g., by studying drugs inducing the cleavage of the prohormone into active BNP). Furthermore, as a future perspective, the specific assay in the same plasma sample of the intact precursor proBNP and of the biologically active peptide BNP, could allow a more accurate estimation of the production/secretion of B-type related peptides from cardiomyocytes and of the global cardiac endocrine function.

  16. 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 Central

    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

  17. 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

  18. 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

  19. 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.

  20. Expression and differential regulation of natriuretic peptides in mouse macrophages.

    PubMed Central

    Vollmar, A M; Schulz, R

    1995-01-01

    The coexpression of the natriuretic peptides ANP, BNP and CNP as well as their differential regulation in mouse macrophages was demonstrated by quantitative PCR, HPLC analysis, and specific radioimmunoassays. Exposure of peritoneal- and bone marrow-derived macrophages to various immunomodulators revealed that bacterial LPS strikingly increases (up to 300-fold) the mRNA coding for CNP as does zymosan (up to 15-fold). In this respect, neither the phorbol ester PMA nor the glucocorticoid dexamethasone had any effect. Examination of macrophages for ANP mRNA showed a similar response to LPS and zymosan, though only a three- to sixfold increase, confirming previous data. In contrast, the concentration of mRNA coding for brain natriuretic peptide in these cells was reduced by dexamethasone (up to twofold) as well as LPS (two- to fivefold). No change was observed upon challenge with zymosan or PMA. The findings at the mRNA level are complemented by their corresponding peptide products. Incubation of macrophages with LPS resulted in a two- and fivefold elevation of intracellular ANP and CNP immunoreactivity, respectively. The amount of peptides released from cells under these conditions was found increased for ANP (threefold) and CNP (10-fold). No changes were observed for both intra- and extracellular brain natriuretic peptide. The coexpression of natriuretic peptides in macrophages as well as their different regulations by immunomodulators suggest discrete functions of these peptides within the immune system. Images PMID:7769089

  1. Scavenger receptor class B type I: a multifunctional receptor.

    PubMed

    Valacchi, Giuseppe; Sticozzi, Claudia; Lim, Yunsook; Pecorelli, Alessandra

    2011-07-01

    The scavenger receptor class B type I (SR-B1) plays an important role in meditating the uptake of HDL-derived cholesterol and cholesteryl ester in the liver and steroidogenic tissues. In addition to being ubiquitous, SR-B1 is a high-density lipoprotein (HDL) receptor in many tissues, though the mechanism by which SR-B1 does this is unclear. Other than its role as an HDL receptor, SR-B1 is also involved in pathogen recognition; its expression can be modulated by lipopolysaccharide and oxidative stress; and it plays a significant role in the uptake of lipid soluble vitamins, such as vitamin E and carotenoids. In this short review, we have summarized the biological aspects to which SR-B1 has been thus far associated.

  2. Values of using QTc and N-terminal fragment of B-type natriuretic peptide as markers for early detection of acute antipsychotic drugs-induced cardiotoxicity.

    PubMed

    Khalaf, Mohamed A M; Abdelrahman, Tarek M; Abbas, Mohamed F

    2011-03-01

    We aimed at studying the acute cardiotoxicity of the most commonly used antipsychotics in Egypt using QTc interval and NT-proBNP as markers for the early detection of such cases. Eighty-two admitted patients, at El-Minia PCC (period from 1-7-2005 to 30-6-2010), were classified into 3 groups: I: acute thioridazine overdose (n = 28), II: acute pimozide overdose (n = 23), and III: acute clozapine overdose (n = 31). Patients were investigated for NT-proBNP level and QTc on admission (day 0) and after 24 h (day 1). All the studied drugs had the ability to induce cardiotoxicity in the form of hypotension and dysrhythmias. Thioridazine and pimozide had potentially serious cardiotoxic effects than clozapine. NT-proBNP levels were elevated significantly in all groups on days 0 and 1 when compared with the reference value and a significant decrease in the same parameter on day 1 when compared with that of day 0 within the same group. QTc showed a significant prolongation in all studied groups on days 0 and 1, and there was a significant shortening of QTc on day 1 when compared with that of day 0 within the same group. A significant positive correlation of NT-proBNP level elevation with QTc prolongation was reported in all groups on days 0 and 1. Serious dysrhythmias were associated with QTc prolongation greater than 500 ms. And it was concluded that NT-proBNP, in adjunction with QTc measurement, may be a valuable and sensitive laboratory biomarker to predict cardiotoxicity of antipsychotic overdose. Larger multicenter studies are still needed to verify this possible relationship.

  3. Inhibition of goby posterior intestinal NaCl absorption by natriuretic peptides and by cardiac extracts.

    PubMed

    Loretz, C A

    1996-01-01

    Natriuretic peptides abolish active Na+ and Cl- absorption across the posterior intestine of the euryhaline goby Gillichthys mirabilis. Inhibition by eel and human natriuretic peptides is dose-dependent with the following sequence of potencies based on experimentally determined ID50 values for inhibition of short-circuit current: eel ventricular natriuretic peptide (78 nmol.l-1), eel atrial natriuretic peptide (156 nmol.l-1), human brain natriuretic peptide (326 nmol.l-1), human alpha atrial natriuretic peptide (1.05 mumol.l-1), and eel C-type natriuretic peptide (75 mumol.l-1). Natriuretic peptides also significantly increase transcellular conductance. The observed sequence of natriuretic peptide potencies is suggestive of cellular mediation by GC-A-type NP-R1 receptors in this tissue; as expected for guanylyl-cyclase-coupled NP-R1 receptors, cyclic GMP mimics the action of natriuretic peptides on the goby intestine. Crude aqueous extracts of goby atrium and ventricle inhibited short circuit current and increased tissue conductance in a dose-dependent manner. Ventricular extract was more potent than atrial extract on both a per organ and per milligram basis.

  4. 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

  5. Serum Glutathione S-Transferase P1 1 in Prediction of Cardiac Function

    PubMed Central

    Andrukhova, Olena; Salama, Mohamed; Rosenhek, Raphael; Gmeiner, Matthias; Perkmann, Thomas; Steindl, Johannes; Aharinejad, Seyedhossein

    2012-01-01

    Background Glutathione S-transferase P1 1 (GSTP1) belongs to the multigene isozyme family involved in cellular response to oxidative stress and apoptosis. Our initial retrospective proteomic analysis suggested that GSTP1 is associated with heart failure (HF). Although pro–B-type natriuretic peptide (proBNP) serves currently as a surrogate diagnostic and prognostic parameter in HF patients, its specificity remains uncertain. We hypothesized that GSTP1 might be a useful serum marker in the monitoring of HF patients. Methods and Results Serum GSTP1 and proBNP were prospectively measured in 193 patients subdivided based on their ejection fraction (EF) either in equal-sized quintiles or predefined EF groups >52%, 43%–52%, 33%–42%, 23%–32% and ≤22%. At a cutoff of ≥231 ng/mL, GSTP1 identified HF patients with EF ≤22% with 81% sensitivity and 83% specificity, and at a cutoff of ≥655 pg/mL, proBNP identified the same patient group with 84% sensitivity and 22% specificity. GSTP1 at a ≥126 ng/mL cutoff identified EF ≤42% with 90% sensitivity and 95% specificity, or proBNP at a ≥396 pg/mL cutoff had 97% sensitivity and 20% specificity. In regression analyses, GSTP1, but not proBNP, discriminated between EF ≤42% and EF >42% in HF patients. Conclusions These results suggest that GSTP1 is strongly associated with HF and could serve as a sensitive and specific marker to predict the ventricular function in HF patients. PMID:22385947

  6. 77 FR 4043 - Scientific Information Request on the Use of Natriuretic Peptide Measurement in the Management of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-26

    ... Natriuretic Peptide Measurement in the Management of Heart Failure AGENCY: Agency for Healthcare Research and... manufacturers of natriuretic peptide measurement assays. Scientific information is being solicited to inform our Comparative Effectiveness Review of Use of Natriuretic Peptide Measurement in the Management of Heart...

  7. 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

  8. Bedside Ultrasonography versus Brain Natriuretic Peptide in Detecting Cardiogenic Causes of Acute Dyspnea

    PubMed Central

    Golshani, Keihan; Esmailian, Mehrdad; Valikhany, Aniseh; Zamani, Majid

    2016-01-01

    Introduction: Acute dyspnea is a common cause of hospitalization in emergency departments (ED).Distinguishing the cardiac causes of acute dyspnea from pulmonary ones is a major challenge for responsible physicians in EDs. This study compares the characteristics of bedside ultrasonography with serum level of blood natriuretic peptide (BNP) in this regard. Methods: This diagnostic accuracy study compares bedside ultrasonography with serum BNP levels in differentiating cardiogenic causes of acute respiratory distress. Echocardiography was considered as the reference test. A checklist including demographic data (age and sex), vital signs, medical history, underlying diseases, serum level of BNP, as well as findings of chest radiography, chest ultrasonography, and echocardiography was filled for all patients with acute onset of dyspnea. Screening characteristics of the two studied methods were calculated and compared using SPSS software, version 20. Results: 48 patients with acute respiratory distress were evaluated (50% female). The mean age of participants was 66.94 ± 16.33 (28-94) years. Based on the results of echocardiography and final diagnosis, the cause of dyspnea was cardiogenic in 20 (41.6%) cases. Bedside ultrasonography revealed the cardiogenic cause of acute dyspnea in 18 cases (0 false positive) and BNP in 44 cases (24 false positives). The area under the ROC curve for bedside ultrasonography and BNP for differentiating the cardiogenic cause of dyspnea were 86.4 (95% CI: 74.6-98.3) and 66.3 (95% CI: 49.8-89.2), respectively (p = 0.0021). Conclusion: It seems that bedside ultrasonography could be considered as a helpful and accurate method in differentiating cardiogenic causes of acute dyspnea in emergency settings. Nevertheless, more study is needed to make a runaway algorithm to evaluate patients with respiratory distress using bedside ultrasonography, which leads to rapid therapeutic decisions in a short time. PMID:27299143

  9. Serum sickness

    MedlinePlus

    Drug allergy - serum sickness; Allergic reaction - serum sickness; Allergy - serum sickness ... penicillin, cefaclor, and sulfa) can cause a similar reaction. Injected proteins such as antithymocyte globulin (used to ...

  10. 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

  11. Cloning of an unusual natriuretic peptide from the South American coral snake Micrurus corallinus.

    PubMed

    Ho, P L; Soares, M B; Maack, T; Gimenez, I; Puorto, G; Furtado, M F; Raw, I

    1997-11-15

    In the course of cloning abundant cDNAs from the South American coral snake Micrurus corallinus venom gland, we characterized a cDNA coding for a putative natriuretic peptide. All the natural natriuretic peptides described so far, possess a ring structure composed of 17 amino acids formed through an S-S bridge which is extended at the N-terminus by few to several amino acids and may be extended at the C-terminus, usually 4-7 amino acids. In contrast, the M. corallinus natriuretic peptide presents several distinct features: (a) the proform of the deduced natriuretic peptide displays an unusual C-terminus extension. This implies that the mature peptide has a long C-terminal tail or it is further extensively processed to result in the mature natriuretic peptide with the expected 4-7 amino-acid extension. (b) the deduced natriuretic peptide presents an unusual internal Cys within the ring structure. This raises the possibility of natriuretic peptides with a smaller ring structure. (c) the putative natriuretic peptide is flanked by two homologous peptides of unknown function. In addition, an analogous peptide was synthesized and assayed on perfused rat kidney, showing a dose-dependent response in urinary volume and sodium excretion. Moreover, northern-blot studies showed that M. corallinus natriuretic peptide transcripts were highly expressed in venom glands, but they were not detectable in other tissues like heart and brain, suggesting a main role for this M. corallinus natriuretic peptide in the venom gland or in the envenomation by this coral snake's bite.

  12. Endothelial C-type natriuretic peptide maintains vascular homeostasis.

    PubMed

    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

    2014-09-01

    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.

  13. 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

  14. Influence of resting tension on immunoreactive atrial natriuretic peptide secretion by rat atria superfused in vitro

    SciTech Connect

    Schiebinger, R.J.; Linden, J.

    1986-07-01

    Atrial natriuretic peptide is a potent diuretic hormone secreted by the atria in response to volume expansion. We examined the effect of resting tension on atrial natriuretic peptide secretion by rat atria superfused in vitro. Left atria were hooked between an electrode and force transducer and superfused with medium 199. The atria were studied at a pacing frequency of 0 or 3 Hz. Atrial natriuretic peptide content of the superfusate was measured by radioimmunoassay. In nonpaced and paced atria, increasing resting tension three- to five-fold caused immunoreactive atrial natriuretic peptide secretion to increase by 35 +/- 5% (mean +/- SEM, n = 6, p less than 0.01) and 30 +/- 3% (n = 4, p less than 0.01), respectively. Lowering resting tension by 50% in nonpaced and paced atria lowered immunoreactive atrial natriuretic peptide secretion by 30 +/- 3% (n = 7, p less than 0.01) and 24 +/- 3% (n = 6, p less than 0.01), respectively. To exclude the possibility that release of norepinephrine or acetylcholine from endogenous nerve endings was mediating this effect, the atria were superfused with the combination of propranolol 0.1 microM, phentolamine 1.0 microM, and atropine 10 microM. These concentrations of the antagonists were 125-fold or higher than their Kd for binding to their respective receptors. The antagonists did not block the rise in immunoreactive atrial natriuretic peptide secretion; neither did they inhibit an established rise in immunoreactive atrial natriuretic peptide secretion induced by increasing the resting tension.

  15. 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

  16. Permeability and contractile responses of collecting lymphatic vessels elicited by atrial and brain natriuretic peptides.

    PubMed

    Scallan, Joshua P; Davis, Michael J; Huxley, Virginia H

    2013-10-15

    Atrial and brain natriuretic peptides (ANP and BNP, respectively) are cardiac hormones released into the bloodstream in response to hypervolaemia or fluid shifts to the central circulation. The actions of both peptides include natriuresis and diuresis, a decrease in systemic blood pressure, and inhibition of the renin-angiotensin-aldosterone system. Further, ANP and BNP elicit increases in blood microvessel permeability sufficient to cause protein and fluid extravasation into the interstitium to reduce the vascular volume. Given the importance of the lymphatic vasculature in maintaining fluid balance, we tested the hypothesis that ANP or BNP (100 nM) would likewise elevate lymphatic permeability (Ps) to serum albumin. Using a microfluorometric technique adapted to in vivo lymphatic vessels, we determined that rat mesenteric collecting lymphatic Ps to rat serum albumin increased by 2.0 ± 0.4-fold (P = 0.01, n = 7) and 2.7 ± 0.8-fold (P = 0.07, n = 7) with ANP and BNP, respectively. In addition to measuring Ps responses, we observed changes in spontaneous contraction amplitude and frequency from the albumin flux tracings in vivo. Notably, ANP abolished spontaneous contraction amplitude (P = 0.005) and frequency (P = 0.006), while BNP augmented both parameters by ∼2-fold (P < 0.01 each). These effects of ANP and BNP on contractile function were examined further by using an in vitro assay. In aggregate, these data support the theory that an increase in collecting lymphatic permeability opposes the absorptive function of the lymphatic capillaries, and aids in the retention of protein and fluid in the interstitial space to counteract volume expansion.

  17. Obesity and natriuretic peptides, BNP and NT-proBNP: mechanisms and diagnostic implications for heart failure.

    PubMed

    Madamanchi, Chaitanya; Alhosaini, Hassan; Sumida, Arihiro; Runge, Marschall S

    2014-10-20

    Many advances have been made in the diagnosis and management of heart failure (HF) in recent years. Cardiac biomarkers are an essential tool for clinicians: point of care B-type natriuretic peptide (BNP) and its N-terminal counterpart (NT-proBNP) levels help distinguish cardiac from non-cardiac causes of dyspnea and are also useful in the prognosis and monitoring of the efficacy of therapy. One of the major limitations of HF biomarkers is in obese patients where the relationship between BNP and NT-proBNP levels and myocardial stiffness is complex. Recent data suggest an inverse relationship between BNP and NT-proBNP levels and body mass index. Given the ever-increasing prevalence of obesity world-wide, it is important to understand the benefits and limitations of HF biomarkers in this population. This review will explore the biology, physiology, and pathophysiology of these peptides and the cardiac endocrine paradox in HF. We also examine the clinical evidence, mechanisms, and plausible biological explanations for the discord between BNP levels and HF in obese patients.

  18. Obesity and Natriuretic Peptides, BNP and NT-proBNP: Mechanisms and Diagnostic Implications for Heart Failure

    PubMed Central

    Madamanchi, Chaitanya; Alhosaini, Hassan; Sumida, Arihiro; Runge, Marschall S.

    2014-01-01

    Many advances have been made in the diagnosis and management of heart failure (HF) in recent years. Cardiac biomarkers are an essential tool for clinicians: point of care B-Type Natriuretic Peptide (BNP) and its N-terminal counterpart (NT-proBNP) levels help distinguish cardiac from non-cardiac causes of dyspnea and are also useful in the prognosis and monitoring of the efficacy of therapy. One of the major limitations of HF biomarkers is in obese patients where the relationship between BNP and NT-proBNP levels and myocardial stiffness is complex. Recent data suggest an inverse relationship between BNP and NT-proBNP levels and body mass index. Given the ever-increasing prevalence of obesity world-wide, it is important to understand the benefits and limitations of HF biomarkers in this population. This review will explore the biology, physiology, and pathophysiology of these peptides and the cardiac endocrine paradox in HF. We also examine the clinical evidence, mechanisms, and plausible biological explanations for the discord between BNP levels and HF in obese patients. PMID:25156856

  19. Mucin model for group B type III streptococcal infection in mice.

    PubMed Central

    Fleming, D O

    1980-01-01

    An experimental murine infection was established by the intraperitoneal injection of a log-phase culture of a laboratory reference strain of Streptococcus agalactiae, Lancefield group B, type III (strain SS620), suspended in sterile hog gastric mucin. The enhancement of streptococcal virulence was measured by a significantly increased mortality in outbred ICR Swiss mice. An inbred C57BL6 strain of mice was resistant to the mucin-bacterial combination. Mucin, treated with Desferal to chelate the iron, did not lose the capacity to enhance the virulence of group B, type III streptococci in ICR Swiss mice. Iron-dextran was not a suitable substitute for mucin and failed to enhance the virulence of group B, type III streptococci. The results of these studies indicate that iron is not the resistance-lowering factor in this group B, type III streptococci-mucin model. PMID:6155334

  20. 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.

  1. Consensus document and recommendations on the use of natriuretic peptides in clinical practice.

    PubMed

    Pascual-Figal, D A; Casademont, J; Lobos, J M; Piñera, P; Bayés-Genis, A; Ordóñez-Llanos, J; González-Juanatey, J R

    2016-01-01

    Natriuretic peptides are a useful laboratory tool for the diagnosis, prognosis and treatment of patients with heart failure. Natriuretic peptides are used in various healthcare settings (consultations, emergency department, hospitalization, laboratory) and by various primary care and specialised professionals. However, their use in clinical practice is still scare and uneven. Properly using and interpreting natriuretic peptides in clinical practice requires a minimum of prelaboratory (pathophysiology), laboratory (methods) and postlaboratory (interpretation and integration of clinical data) expertise. The objective of this consensus document, developed by several scientific societies, is to update the necessary concepts and expertise on natriuretic peptides that enable its application in the diagnosis, prognosis and treatment of heart failure, in various healthcare environments.

  2. 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

  3. Can Natriuretic Peptides be Used to Guide Therapy?

    PubMed Central

    Lupón, Josep; Jaffe, Allan S.

    2016-01-01

    Over the last 15 years, the hypothesis that intensified treatment directed at reducing natriuretic peptide (NP) concentrations may improve the outcomes of patients with heart failure (HF) has been scrutinized in several prospective clinical trials, with conflicting results. Collectively, however, the data suggest that NP concentrations may be useful in guiding HF management and improving HF-related morbidity and mortality. In this review, we summarize the existing data investigating the use of NPs as targets for outpatient HF therapy. We focus on the information gathered in randomized clinical trials and comprehensive meta-analyses, and also on the recommendations of international guidelines (primarily guidelines from the European Society of Cardiology and the American College of Cardiology/American Heart Association). Although the results for this approach are promising overall, additional well-designed prospective randomized controlled trials (e.g., the GUIDE-IT trial) are necessary to confirm or refute the utility of NP-guided outpatient HF management.

  4. 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

  5. Atrial Natriuretic Peptide in Cardiovascular Biology and Disease (NPPA)

    PubMed Central

    Song, Wei; Wang, Hao; Wu, Qingyu

    2015-01-01

    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

  6. 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

  7. Diuretic and natriuretic effects of sorbinil, an aldose reductase inhibitor.

    PubMed

    Springate, J E; Feld, L G; Van Liew, J B; Fildes, R D; Acara, M A

    1991-04-01

    The renal effects of sorbinil, an aldose reductase inhibitor that interferes with the conversion of glucose to sorbitol, were studied in rats and rabbits before and after fluid deprivation. The intracellular osmolar solute, sorbitol, is found in increasing concentrations from cortex to medulla in the kidney and may be involved in the urinary concentrating mechanism. Oral administration of sorbinil in the rabbit resulted in significant increases in urine flow rate and sodium excretion with a tendency toward decreased urine osmolality and increased potassium excretion both before and after water deprivation. When fluid intake was controlled in the rat study, significant increases in urine flow rate and sodium and potassium excretion and a significant decrease in urine osmolality occurred only in response to fluid deprivation. Thus, sorbinil has diuretic and natriuretic properties and may prevent the normal concentration of urine in the antidiuretic animal.

  8. Immunoreactive atrial natriuretic peptide in the guinea pig spleen

    SciTech Connect

    Vollmar, A.M.; Friedrich, A.; Schulz, R. )

    1989-01-01

    The presence of immunoreative ANP precursor-like material in the guinea pig spleen is suggested. This is based on the following experimental evidence: An acidic extract of guinea pig spleen analyzed by Sephadex G-50 gel filtration contained 4.6 pmol/g wet tissue immunoreactive atrial natriuretic peptide (IR-ANP), IR-ANP coeluting with 15 kDa synthetic ANP (2-126). Gel filtrated IR-ANP material was further submitted to reverse phase high performance liquid chromatography and monitored by radioimmunoassay employing two antisera. One antiserum recognizes the C-terminal of ANP (1-126), the second is directed against the N-terminal sequence. Both antisera revealed material eluting with synthetic ANP (2-126). Furthermore, immunohistochemical analysis suggests this ANP-like material to be localized mainly at the periphery of the white pulp of the spleen. These findings link ANP with the immune system.

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

    PubMed

    Rose, Robert A; Giles, Wayne R

    2008-01-15

    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.

  10. 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

  11. 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

  12. Brain natriuretic peptide: Much more than a biomarker.

    PubMed

    Calzetta, Luigino; Orlandi, Augusto; Page, Clive; Rogliani, Paola; Rinaldi, Barbara; Rosano, Giuseppe; Cazzola, Mario; Matera, Maria Gabriella

    2016-10-15

    Brain natriuretic peptide (BNP) modulates several biological processes by activating the natriuretic peptide receptor A (NPR-A). Atria and ventricles secrete BNP. BNP increases natriuresis, diuresis and vasodilatation, thus resulting in a decreased cardiac workload. BNP and NT-proBNP, which is the biologically inactive N-terminal portion of its pro-hormone, are fast and sensitive biomarkers for diagnosing heart failure. The plasma concentrations of both BNP and NT-proBNP also correlate with left ventricular function in patients with acute exacerbation of COPD, even without history of heart failure. Several studies have been conducted in vitro and in vivo, both in animals and in humans, in order to assess the potential role of the NPR-A activation as a novel therapeutic approach for treating obstructive pulmonary disorders. Unfortunately, these studies have yielded conflicting results. Nevertheless, further recent specific studies, performed in ex vivo models of asthma and COPD, have confirmed the bronchorelaxant effect of BNP and its protective role against bronchial hyperresponsiveness in human airways. These studies have also clarified the intimate mechanism of action of BNP, represented by an autocrine loop elicited by the activation of NPR-A, localized on bronchial epithelium, and the relaxant response of the surrounding ASM, which does not expresses NPR-A. This review explores the teleological activities and paradoxical effects of BNP with regard to chronic obstructive respiratory disorders, and provides an excursus on the main scientific findings that explain why BNP should be considered much more than a biomarker. PMID:27447810

  13. 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

  14. 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.

  15. Efficacy of different doses of atorvastatin treatment on serum levels of 8-hydroxy-guanin (8-OHdG) and cardiac function in patients with ischemic cardiomyopathy

    PubMed Central

    Jin, Yu; Qiu, Chunguang; Zheng, Qiangsun; Liu, Ling; Liu, Zhiqiang; Wang, Yi

    2015-01-01

    Objective: To compare the efficacy of 40 mg and l0 mg atorvastatin on serum levels of 8-Hydroxy-Guanin (8-OHdG) and the cardiac function in patients with ischemic cardiomyopathy (ICM). Methods: One hundred twenty three hospitalized ICM patients and 120 healthy controls were included in this study. All subjects were randomly divided into two groups: 10 mg/d atorvastatin group (n=62) and 40 mg/d atorvastatin group (n=61). Serum levels of C-reactive protein (CRP), creatine kinase, glutamic-pyruvic transaminase, lipids and B-type natriuretic peptide (BNP) were tested in all subjects both at the initial phase and the terminal phase of this study. Adverse drug reaction events were recorded in this study. Echocardiographic method was applied to compare the cardiac function before and after treatment in the double blind study. Serum 8-OHdG levels were tested by enzyme-linked immunosorbent assay (ELISA) before and after treatment, and the results in atorvastatin treatment groups were compared with the healthy controls. Results: Serum 8-OHdG levels in ICM patients were significantly higher than that in normal control groups (p<0.05). There was significant difference of Serum 8-OHdG levels in 40 mg/d atorvastatin group (p<0.05), but was no significant difference in 10 mg/d atorvastatin group before and after the treatment. The 8-OHdG level in 40 mg/d atorvastatin group was significantly lower than that in 10 mg/d atorvastatin group before the treatment as well as after the treatment (p<0.05). The systolic and diastolic function improved significantly in 40 mg/d atorvastatin group before and after treatment, as well as in comparison with 10 mg/d atorvastatin group (p<0.05). Conclusion: Serum 8-OHdG possibly plays an important role in the pathogenesis of ICM. Atorvastatin is safe and effective in ICM treatment; furthermore atorvastatin which also has independent lipid lowering effect, is significantly better in the dose of 40 mg/day. PMID:25878611

  16. Near-infrared spectroscopic survey of B-type asteroids: Compositional analysis

    NASA Astrophysics Data System (ADS)

    de León, J.; Pinilla-Alonso, N.; Campins, H.; Licandro, J.; Marzo, G. A.

    2012-03-01

    We present near-infrared spectra of 23 B-type asteroids obtained with the NICS camera-spectrograph at the 3.56 m Telescopio Nazionale Galileo. We also compile additional visible and near-infrared spectra of another 22 B-type asteroids from the literature. A total of 45 B-types are analyzed. No significant trends in orbital properties of our sample were detected when compared with all known B-types and all known asteroids. The reflectance spectra of the asteroids in the 0.8-2.5 μm range show a continuous shape variation, from a monotonic negative (blue) slope to a positive (red) slope. This continuous spectral trend is filling the gap between the two main groups of B-types published by Clark et al. ([2010]. J. Geophys. Res., 115, 6005-6027). We found no clear correlations between the spectral slope and the asteroids’ sizes or heliocentric distances. We apply a clustering technique to reduce the volume of data to six optimized “average spectra” or “centroids”, representative of the whole sample. These centroids are then compared against meteorite spectra from the RELAB database. We found carbonaceous chondrites as the best meteorite analogs for the six centroids. There is a progressive change in analogs that correlates with the spectral slope: from CM2 chondrites (water-rich, aqueously altered) for the reddest centroid, to CK4 chondrites (dry, heated/thermally altered) for the bluest one.

  17. A case of marked diuresis by combined dopamine and atrial natriuretic peptide administration without renal injury in acute decompensated heart failure.

    PubMed

    Kamiya, Masataka; Sato, Naoki; Akiya, Mai; Okazaki, Hirotake; Takahashi, Yasuhiro; Mizuno, Kyoichi

    2013-01-01

    Renal injury is an important factor for worsening outcome in acute decompensated heart failure (ADHF). An 81-year-old woman was admitted due to ADHF with dyspnea and mild peripheral edema. The patient was managed with intravenous administration of atrial natriuretic peptide (ANP) at a dose of 0.0125 μg/kg/minute, which did not control volume overload even at an increased dose of 0.025 μg/kg/minute. After a low dose of dopamine (DA) of 1.0 μg/kg/ minute was added, urine output increased markedly to 120 from 30 mL/hour. Furthermore, her heart rate decreased to 80-100 from 120 bpm and the congestion improved with a reduced brain natriuretic peptide level. Interestingly, the combination of ANP and DA therapy reduced serum creatinine as well as the levels of urinary liver-type fatty acid binding protein, a novel reno-tubular stress marker, by 98.9%, and an oxidative stress marker, urinary 8-hydroxydeoxyguanosine, by 88.2% from baseline levels. Thus, this ADHF patient, a nonresponder to ANP alone, improved without renal injury when administered combination therapy consisting of low doses of ANP and DA, suggesting that this combined therapy might be useful for better management of ADHF in patients without diuretic responses with ANP alone. Further prospective studies are warranted.

  18. Atrial natriuretic peptide (ANP) inhibits DMBA/croton oil induced skin tumor growth by modulating NF-κB, MMPs, and infiltrating mast cells in swiss albino mice.

    PubMed

    Subramanian, Vimala; Vellaichamy, Elangovan

    2014-10-01

    Cardiac hormone atrial natriuretic peptide (ANP) and its receptor, natriuretic peptide receptor-A (NPR-A) are implicated as a vital regulator of cancer cell growth and tumor progression. However, the underlying mechanism by which ANP opposes the cancer growth in in-vivo remains unknown. Herein, we investigated the anti-cancer activity of ANP on 7, 12-dimethyl benzanthracence (DMBA)/Croton oil- induced two-step skin carcinogenic mouse model. Skin tumor incidence and tumor volume were recorded during the experimental period of 16 weeks. ANP (1 μg/kg body weight/alternate days for 4 weeks) was injected subcutaneously from the 13th week of DMBA/Croton oil induction. ANP treatment markedly inhibited the skin tumor growth (P<0.001). A significant reduction in the level of NF-κB activation (P<0.001), infiltrating mast cell count (P<0.01) and MMP-2/-9 (P<0.001, respectively) were noticed in the ANP treated mice skin tissue. Further, ANP treatment revert back the altered levels of serum LDH-4, C-reactive protein (CRP), and enzymatic antioxidants (SOD and CAT activities) to near normal level. Taken together, the results of this study suggest that ANP opposes the skin carcinogenesis by suppressing the inflammatory response and MMPs.

  19. [A case of lymphocyst infection caused by vanB type VRE].

    PubMed

    Imafuku, Y; Yoshida, H; Sato, T; Yamada, H; Sato, A; Hiramatsu, K

    1999-05-01

    A case of post-operative abdominal lymphocyst infection caused by vanB type vancomycin resistant enterococcus (VRE) in reported. A 27-year-old female was diagnosed as pregnancy with uterine cervical carcinoma and underwent Cesarean section and radical hysterectomy. After discharge, she developed a high fever which was diagnosed as a lymphocyst infection. Microbiological examination demonstrated the presence of vanB type VRE in the cyst fluid. Cyst cleaning and minocyclin injection were effective. This is the first case of VRE infection in Japan.

  20. Atrial and brain natriuretic peptides stimulate the production and secretion of C-type natriuretic peptide from bovine aortic endothelial cells.

    PubMed Central

    Nazario, B; Hu, R M; Pedram, A; Prins, B; Levin, E R

    1995-01-01

    C-type natriuretic peptide (CNP) is a member of the natriuretic peptide family which is produced in vascular endothelial cells and may play an important paracrine role in the vasaculature. We sought to determine the regulation of CNP production by other vasoactive peptides from cultured aortic endothelial cells. The vasoconstrictors endothelin-1 and angiotensin II had little effect on the basal secretion of CNP. In contrast, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) strongly stimulated the secretion of CNP. BNP caused as much as a 400-fold enhancement above the basal accumulated secretion of CNP over 24 h at a concentration of 1 microM; this was 20 times greater than the stimulatory effect of ANP, BNP and ANP also significantly enhanced the production of new CNP protein (translation) and mRNA expressed in the BAEC. In contrast, C-ANP-4-23, a truncated form of ANP which selectively binds to the natriuretic peptide clearance receptor, did not stimulate CNP secretion. The enhanced production and secretion of CNP, caused by either ANP or BNP, was significantly prevented by LY 83583, an inhibitor of cGMP generation, and was also attenuated by KT 5823, an inhibitor of cGMP-dependent protein kinase. Our results indicate that ANP and BNP can stimulate CNP production through a guanylate cyclase receptor on endothelial cells. BNP is a much more potent stimulator of CNP secretion, compared to ANP. Our findings suggest that the vasodilatory, and anti-mitogenic effects of ANP and BNP in the vasculature could occur in part through CNP production and subsequent action if these interactions occur in vivo. Images PMID:7883964

  1. Specific binding of atrial natriuretic factor in brain microvessels

    SciTech Connect

    Chabrier, P.E.; Roubert, P.; Braquet, P.

    1987-04-01

    Cerebral capillaries constitute the blood-brain barrier. Studies of specific receptors (neurotransmitters or hormones) located on this structure can be performed by means of radioligand-binding techniques on isolated brain microvessels. The authors examined on pure bovine cerebral microvessel preparations the binding of atrial natriuretic factor (ANF), using /sup 125/I-labeled ANF. Saturation and competition experiments demonstrated the presence of a single class of ANF-binding sites with high affinity and with a binding capacity of 58 fmol/mg of protein. The binding of /sup 125/I-labeled ANF to brain microvessels is specific, reversible, and time dependent, as is shown by association-dissociation experiments. The demonstration of specific ANF-binding sites on brain microvessels supposes a physiological role of ANF on brain microvasculature. The coexistence of ANF and angiotensin II receptors on this cerebrovascular tissue suggests that the two circulating peptides may act as mutual antagonists in the regulation of brain microcirculation and/or blood-brain barrier function.

  2. Pharmacologic Atrial Natriuretic Peptide Reduces Human Leg Capillary Filtration

    NASA Technical Reports Server (NTRS)

    Watenpaugh, Donald E.; Vissing, Susanne F.; Lane, Lynda D.; Buckey, Jay C.; Firth, Brian G.; Erdman, William; Hargens, Alan R.; Blomqvist, C. Gunnar

    1995-01-01

    Atrial natriuretic peptide (ANP) is produced and secreted by atrial cells. We measured calf capillary filtration rate with prolonged venous-occlusion plethysmography of supine healthy male subjects during pharmacologic infusion of ANP (48 pmol/kg/min for 15 min; n = 6) and during placebo infusion (n = 7). Results during infusions were compared to prior control measurements. ANP infusion increased plasma (ANP) from 30 +/- 4 to 2,568 +/- 595 pmol/L. Systemic hemoconcentration occurred during ANP infusion: mean hematocrit and plasma colloid osmotic pressure increased 4.6 and 11.3%, respectively, relative to preinfusion baseline values (p less than 0.05). Mean calf filtration, however, was significantly reduced from 0.15 to 0.08 ml/100 ml/min with ANP. Heart rate increased 20% with ANP infusion, whereas blood pressure was unchanged. Calf conductance (blood flow/ arterial pressure) and venous compliance were unaffected by ANP infusion. Placebo infusion had no effect relative to prior baseline control measurements. Although ANP induced systemic capillary filtration, in the calf, filtration was reduced with ANP. Therefore, pharmacologic ANP infusion enhances capillary filtration from the systemic circulation, perhaps at upper body or splanchnic sites or both, while having the opposite effect in the leg.

  3. Pharmacologic Atrial Natriuretic Peptide Reduces Human Leg Capillary Filtration

    NASA Technical Reports Server (NTRS)

    Watenpaugh, Donald E.; Vissing, Susanne F.; Lane, Lynda D.; Buckey, Jay C.; Firth, Brian G.; Erdman, William; Hargens, Alan R.; Blomqvist, C. Gunnar

    1995-01-01

    Atrial natriuretic peptide (ANP) is produced and secreted by atrial cells. We measured calf capillary filtration rate with prolonged venous-occlusion plethys-mography of supine health male subjects during pharmacologic infusion of ANP (48 pmol/kg/min for 15 min; n equals 6) and during placebo infusion (n equals 7). Results during infusions were compared to prior control measurements. ANP infusion increased plasma (ANP) from 30 plus or minus 4 to 2,568 plus or minus 595 pmol/L. Systemic hemoconcentration occurred during ANP infusion; mean hematocrit and plasma colloid osmotic pressure increased 4.6 and 11.3 percent respectively, relative to pre-infusion baseline values (p is less than 0.05). Mean calf filtration, however was significantly reduced from 0.15 to 0.08 ml/100 ml/min with ANP. Heart rate increased 20 percent with ANP infusion, wheras blood pressure was unchanged. Calf conductance (blood flow/arterial pressure) and venous compliance were unaffected by ANP infusion. Placebo infusion had no effect relative to prior baseline control measurements. Although ANP induced systemic capillary filtration, in the calf, filtration was reduced with ANP. Therefore, phamacologic ANP infusion enhances capillary filtration from the systemic circulation, perhaps at upper body or splanchic sites or both, while having the opposite effect in the leg.

  4. Diuretic and natriuretic activity of two mistletoe species in rats

    PubMed Central

    Jadhav, Namita; Patil, C. R.; Chaudhari, K. B.; Wagh, J. P.; Surana, S. J.; Jadhav, R. B.

    2010-01-01

    In different cultural groups, the hemiparasitic plants of the families Loranthaceae and Viscaceae (mistletoes) are frequently used in the treatment of hypertension and/or as diuretic agents. However, it remains unclear as to what commonality makes them diuretic agents or a remedy for hypertension. In this article, the diuretic activity of methanol extracts of Viscum articulatum (VA) Burm. f. and Helicanthus elastica (HE) (Ders.) Dans. in rats is reported. The extracts were administered orally at doses of 100, 200 and 400 mg/kg to rats that had been fasted and deprived of water for 18 hours. Investigations were carried out for diuretic, saluretic and natriuretic effects. The polyphenolic and triterpenoid contents were determined quantitatively using chemical assays and high performance liquid chromatography (HPLC) analysis, respectively. The extracts of VA and HE demonstrated significant and dose-dependent diuretic activity in rats. It was found that while VA mimics the furosemide pattern, HE demonstrated a dose-dependent increase in diuresis, along with an increase in potassium-sparing effects. Phytochemical analysis revealed that polyphenolics and triterpenoids, such as oleanolic acid and lupeol, are the major phytochemicals involved. It was also found that in different combinations, these phytochemicals differed in the way they influenced the electrolyte excretion. A higher content of polyphenolics in association with lower triterpenoid content was found to favor potassium-sparing effects. PMID:21808540

  5. Atrial natriuretic peptide prevents cancer metastasis through vascular endothelial cells

    PubMed Central

    Nojiri, Takashi; Hosoda, Hiroshi; Tokudome, Takeshi; Miura, Koichi; Ishikane, Shin; Otani, Kentaro; Kishimoto, Ichiro; Shintani, Yasushi; Inoue, Masayoshi; Kimura, Toru; Sawabata, Noriyoshi; Minami, Masato; Nakagiri, Tomoyuki; Funaki, Soichiro; Takeuchi, Yukiyasu; Maeda, Hajime; Kidoya, Hiroyasu; Kiyonari, Hiroshi; Shioi, Go; Arai, Yuji; Hasegawa, Takeshi; Takakura, Nobuyuki; Hori, Megumi; Ohno, Yuko; Miyazato, Mikiya; Mochizuki, Naoki; Okumura, Meinoshin; Kangawa, Kenji

    2015-01-01

    Most patients suffering from cancer die of metastatic disease. Surgical removal of solid tumors is performed as an initial attempt to cure patients; however, surgery is often accompanied with trauma, which can promote early recurrence by provoking detachment of tumor cells into the blood stream or inducing systemic inflammation or both. We have previously reported that administration of atrial natriuretic peptide (ANP) during the perioperative period reduces inflammatory response and has a prophylactic effect on postoperative cardiopulmonary complications in lung cancer surgery. Here we demonstrate that cancer recurrence after curative surgery was significantly lower in ANP-treated patients than in control patients (surgery alone). ANP is known to bind specifically to NPR1 [also called guanylyl cyclase-A (GC-A) receptor]. In mouse models, we found that metastasis of GC-A–nonexpressing tumor cells (i.e., B16 mouse melanoma cells) to the lung was increased in vascular endothelium-specific GC-A knockout mice and decreased in vascular endothelium-specific GC-A transgenic mice compared with control mice. We examined the effect of ANP on tumor metastasis in mice treated with lipopolysaccharide, which mimics systemic inflammation induced by surgical stress. ANP inhibited the adhesion of cancer cells to pulmonary arterial and micro-vascular endothelial cells by suppressing the E-selectin expression that is promoted by inflammation. These results suggest that ANP prevents cancer metastasis by inhibiting the adhesion of tumor cells to inflamed endothelial cells. PMID:25775533

  6. Atrial natriuretic factor in maternal and fetal sheep

    SciTech Connect

    Cheung, C.Y.; Gibbs, D.M.; Brace, R.A.

    1987-02-01

    To determine atrial natriuretic factor (ANF) concentrations in the circulation and body fluids of adult pregnant sheep and their fetuses, pregnant ewes were anesthetized with pentobarbital sodium, and the fetuses were exteriorized for sampling. ANF concentration, as measured by radioimmunoassay, was 47 +/- 6 (SE) pg/ml in maternal plasma, which was significantly higher than the 15 +/- 3 pg/ml in maternal urine. In the fetus, plasma ANF concentration was 265 +/- 49 pg/ml, 5.6 times that in maternal plasma. No umbilical arterial and venous difference in ANF concentration was observed. Fetal urine ANF concentration was significantly lower than that in fetal plasma, and was similar to that measured in amniotic and allantoic fluid. In chronically catheterized maternal and fetal sheep, fetal plasma ANF was again 5.1 times that in maternal plasma, and these levels were not different from those measured in acutely anesthetized animals. These results demonstrate that immunoreactive ANF is present in the fetal circulation at levels higher than those found in the mother. The low concentration of ANF in fetal urine suggests that ANF is probably metabolized and/or reabsorbed by the fetal kidney.

  7. Atrial natriuretic factor binding sites in experimental congestive heart failure

    SciTech Connect

    Bianchi, C.; Thibault, G.; Wrobel-Konrad, E.; De Lean, A.; Genest, J.; Cantin, M. )

    1989-10-01

    A quantitative in vitro autoradiographic study was performed on the aorta, renal glomeruli, and adrenal cortex of cardiomyopathic hamsters in various stages of heart failure and correlated, in some instances, with in vivo autoradiography. The results indicate virtually no correlation between the degree of congestive heart failure and the density of 125I-labeled atrial natriuretic factor ((Ser99, Tyr126)ANF) binding sites (Bmax) in the tissues examined. Whereas the Bmax was increased in the thoracic aorta in moderate and severe heart failure, there were no significant changes in the zona glomerulosa. The renal glomeruli Bmax was lower in mild and moderate heart failure compared with control and severe heart failure. The proportion of ANF B- and C-receptors was also evaluated in sections of the aorta, adrenal, and kidney of control and cardiomyopathic hamsters with severe heart failure. (Arg102, Cys121)ANF (des-(Gln113, Ser114, Gly115, Leu116, Gly117) NH2) (C-ANF) at 10(-6) M displaced approximately 505 of (Ser99, Tyr126)125I-ANF bound in the aorta and renal glomeruli and approximately 20% in the adrenal zona glomerulosa in both series of animals. These results suggest that ANF may exert a buffering effect on the vasoconstriction of heart failure and to a certain extent may inhibit aldosterone secretion. The impairment of renal sodium excretion does not appear to be related to glomerular ANF binding sites at any stage of the disease.

  8. Atrial natriuretic peptide increases resistance to venous return in rats

    SciTech Connect

    Chien, Y.W.; Frohlich, E.D.; Trippodo, N.C.

    1987-05-01

    To examine mechanisms by which administration of atrial natriuretic peptide (ANP) decreases venous return, the authors compared the hemodynamic effects of ANP furosemide (FU), and hexamethonium (HEX) with those of vehicle (VE) in anesthetized rats. Compared with VE, ANP reduced mean arterial pressure, central venous pressure, and cardiac index and increased calculated resistance to venous return. /sup 141/Ce-labeled microspheres were used to determine cardiac output. Mean circulatory filling pressure, distribution of blood flow between splanchnic organs and skeletal muscles, and total peripheral resistance remained unchanged. FU increased urine output similar to that of ANP, yet produced no hemodynamic changes, dissociating diuresis, and decreased cardiac output. HEX lowered arterial pressure through a reduction in total peripheral resistance without altering cardiac output or resistance to venous return. The results confirm previous findings that ANP decreases cardiac output through a reduction in venous return and suggest that this results partly from increased resistance to venous return and not from venodilation or distribution of blood flow.

  9. Analytical Issues with Natriuretic Peptides - has this been Overly Simplified?

    PubMed

    Semenov, Alexander G; Katrukha, Alexey G

    2016-08-01

    Natriuretic peptides (NPs) were first described as cardiac biomarkers more than two decades ago. Since that time, numerous studies have confirmed NPs' diagnostic and prognostic utilities as biomarkers of myocardial function. However, we must now admit that despite the NPs' relatively long period of use in clinical practice, our understanding of the biochemistry and the variety of circulating forms of NPs, as well as of their potential as biomarkers, remains far from being complete and comprehensive. The highly complex nature and wide diversity of circulating forms of NPs make their accurate measurements in plasma far more complex than initially believed. A highly simplistic view of the NPs' use is that elevated values of NPs indicate the severity of heart failure and thus reflect the prognosis. However, as shown by a variety of studies, deep understanding of how the NP system works will be required for correct interpretation of test results in routine practice of cardiovascular disease. In this review, we summarize the recent advances in understanding of the complexity of the NP system and discuss related analytical issues, which open new horizons, as well as challenges for clinical diagnostics. PMID:27683533

  10. An Emerging Role of Natriuretic Peptides: Igniting the Fat Furnace to Fuel and Warm the Heart.

    PubMed

    Palmer, Biff F; Clegg, Deborah J

    2015-12-01

    Natriuretic peptides are produced in the heart and have been well characterized for their actions in the cardiovascular system to promote diuresis and natriuresis, thereby contributing to maintenance of extracellular fluid volume and vascular tone. For this review, we scanned the literature using PubMed and MEDLINE using the following search terms: beiging, adipose tissue, natriuretic peptides, obesity, and metabolic syndrome. Articles were selected for inclusion if they represented primary data or review articles published from 1980 to 2015 from high-impact journals. With the advent of the newly approved class of drugs that inhibit the breakdown of natriuretic peptides, thereby increasing their circulation, we highlight additional functions for natriuretic peptides that have recently become appreciated, including their ability to drive lipolysis, facilitate beiging of adipose tissues, and promote lipid oxidation and mitochondrial respiration in skeletal muscle. We provide evidence for new roles for natriuretic peptides, emphasizing their ability to participate in body weight regulation and energy homeostasis and discuss how they may lead to novel strategies to treat obesity and the metabolic syndrome.

  11. 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

  12. 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

  13. Binding sites of atrial natriuretic peptide in tree shrew adrenal gland

    SciTech Connect

    Fuchs, E.; Shigematsu, K.; Saavedra, J.M.

    1986-09-01

    Adrenal gland binding sites for atrial natriuretic peptide-(99-126) (ANP) were quantitated in tree shrew (Tupaia belangeri) by incubation of adrenal sections with (3-(/sup 125/I)-iodotyrosyl28) atrial natriuretic peptide-(99-126), followed by autoradiography with computerized microdensitometry. In the adrenal glands, there are three types of ANP binding sites. One is located in the zona glomerulosa (BMax 84 +/- 6 fmol/mg protein; Kd 122 +/- 9 pM); the second in the zona fasciculata and reticularis (BMax 29 +/- 2 fmol/mg protein; Kd 153 +/- 6 pM) and the third in the adrenal medulla (BMax 179 +/- 1 fmol/mg protein; Kd 70 +/- 2 pM). Besides the influence of ANP on the regulation of adrenocortical mineralcorticoid and glucocorticoid secretion our findings raise the possibility for a local site of action of atrial natriuretic peptide in the regulation of adrenomedullary catecholamines in the tree shrew, primates and man.

  14. Radioimmunoassay and characterization of atrial natriuretic peptide in human plasma

    SciTech Connect

    Yandle, T.G.; Espiner, E.A.; Nicholls, M.G.; Duff, H.

    1986-07-01

    A RIA for alpha-human atrial natriuretic peptide (alpha hANP) in plasma was developed and used to study the immunoreactive components secreted by the heart and circulating in peripheral venous plasma. The assay used (125I)diiodotyrosyl-alpha hANP, purified by high pressure liquid chromatography (HPLC), and a C-terminal-specific antiserum purchased from Peninsula Laboratories. Serial dilution curves of coronary sinus plasma samples were parallel with the standard curve, but significant nonparallelism was found in peripheral plasma samples of low immunoreactivity. When plasma was extracted using C-18 Sep-Pak cartridges, serial dilution curves from both coronary sinus and peripheral plasma samples were parallel to the standard curve. Although values for plasma samples assayed before and after extraction agreed closely (r = 0.99; n = 76), immunoreactive ANP in unextracted plasma was consistently greater (70-79 pmol/liter) than in extracts of plasma, suggesting non-specific interference by a component in plasma when assayed without extraction. Mean plasma immunoreactive ANP in 19 normal subjects consuming a normal salt intake was 14 +/- 1 (+/- SE) pmol/liter. In 5 normal men, increasing dietary sodium intake from 10 to 200 mmol sodium/day was associated with a 2-fold increment in ANP levels, and similar changes accompanied acute sodium loading using iv saline. Elevated values were found in patients with congestive heart failure (mean, 58 pmol/liter; range, 0-200; n = 9), chronic renal failure (mean, 118 pmol/liter; range, 30-290; n = 8), and primary aldosteronism (range, 32-90 pmol/liter; n = 3). HPLC and gel chromatographic analysis of the immunoreactive material found in coronary sinus plasma extracts showed that a large amount of the material eluted in the position of alpha hANP.

  15. Regulation of atrial natriuretic peptide receptors in the rat brain

    SciTech Connect

    Saavedra, J.M.

    1987-06-01

    We have studied the localization, kinetics, and regulation of receptors for the circulating form of the atrial natriuretic peptide (ANP; 99-126) in the rat brain. Quantitative autoradiographic techniques and a /sup 125/I-labeled ligand, /sup 125/I-ANP (99-126), were employed. After in vitro autoradiography, quantification was achieved by computerized microdensitometry followed by comparison with /sup 125/I-standards. ANP receptors were discretely localized in the rat brain, with the highest concentrations in circumventricular organs, the choroid plexus, and selected hypothalamic nuclei involved in the production of the antidiuretic hormone vasopressin and in blood-pressure control. Spontaneously (genetic) hypertensive rats showed much lower numbers of ANP receptors than normotensive controls in the subfornical organ, the area postrema, the nucleus of the solitary tract, and the choroid plexus. These changes are in contrast to those observed for receptors of angiotensin II, another circulating peptide with actions opposite to those of ANP. Under conditions of acute dehydration after water deprivation, as well as under conditions of chronic dehydration such as those present in homozygous Brattleboro rats, there was an up-regulation of ANP receptors in the subfornical organ. Our results indicate that in the brain, circumventricular organs contain ANP receptors which could respond to variations in the concentration of circulating ANP. In addition, brain areas inside the blood-brain barrier contain ANP receptors probably related to the endogenous, central ANP system. The localization of ANP receptors and the alterations in their regulation present in genetically hypertensive rats and after dehydration indicate that brain ANP receptors are probably related to fluid regulation, including the secretion of vasopressin, and to cardiovascular function.

  16. Functional atrial natriuretic peptide receptor in human adrenal tumor

    SciTech Connect

    Shionoiri, H.; Hirawa, N.; Takasaki, I.; Ishikawa, Y.; Oda, H.; Minamisawa, K.; Sugimoto, K.; Matsukawa, T.; Ueda, S.; Miyajima, E.

    1989-01-01

    The effects of synthetic human atrial natriuretic peptide (ANP) on the release of catecholamines, aldosterone, or cortisol were observed in human adrenal tumors obtained surgically from patients with pheochromocytoma, primary aldosteronism, or Cushing's syndrome, respectively. Each tumor tissue or adjacent normal cortical tissue was sectioned into slices, which were incubated in medium-199 in the presence or absence of adrenocorticotrophin (ACTH) and ANP. The amounts of epinephrine, norepinephrine, aldosterone, or cortisol released into the medium were measured. Existence of ANP receptors on the adrenal tissues was examined by binding assays, affinity labeling, and immunohistochemistry. Release of catecholamines from pheochromocytoma tissues was inhibited by ANP, and the presence of the ANP receptor on pheochromocytoma was further demonstrated by both binding assays and affinity labeling; Scatchard analysis revealed a single class of binding sites for ANP with a Kd of 1.0 nM and a Bmax of 0.4 pmol/mg of protein and the molecular size was estimated as 140 and a 70 kDa under nonreducing and reducing conditions, respectively. The presence of ANP receptors in pheochromocytoma was demonstrated by immunohistochemistry. ANP inhibited both basal and ACTH-stimulated aldosterone secretion in the slices of normal cortex, and localization of ANP receptors in zona glomerulosa cells was also demonstrated. However, ANP did not inhibit basal and ACTH-stimulated aldosterone and cortisol secretion in both tissue slices from aldosteronoma and Cushing's adenoma. Consistent with these observations, the absence of ANP receptors in adenoma tissues was determined by binding assays, affinity labeling, and immunohistochemistry.

  17. Changes of adrenomedullin and natriuretic peptides in patients with adrenal medullary hyperplasia prior to and following pharmacological therapy and adrenalectomy

    PubMed Central

    Zhou, Pang-Hu; Shi, Lei; Hu, Wei; Zhang, Xiao-Bin; Wang, Wei; Zhang, Li-Jun

    2016-01-01

    The aim of the present study was to investigate the pathophysiological functions of adrenomedullin (ADM), atrial and brain natriuretic peptides (ANP and BNP) in patients with adrenal medullary hyperplasia (AMH). Plasma ADM, ANP and BNP concentrations were measured in 20 patients with AMH, 35 patients with essential hypertension (EH), and 40 healthy control subjects. Following effective antihypertensive therapy, the values in AMH and EH patients were measured again and laparoscopic adrenalectomy was performed for AMH patients. At 2 weeks after surgery, the three peptides were measured again. The AMH patients had higher plasma concentrations of ADM, ANP and BNP compared with the EH and control subjects. There were significant differences in the values of ADM, ANP and BNP between adrenal vein and inferior vena cava and between AMH and contralateral adrenal vein. Plasma ADM concentration was correlated with serum epinephrine and norepinephrine and urine vanillylmandelic acid, in addition to systolic and diastolic blood pressure, left ventricular ejection fraction, left ventricular mass index and ANP and BNP values in the AMH group. Following antihypertensive treatment, ADM, ANP and BNP were significantly decreased in EH patients, but remained unchanged in AMH subjects. However, these concentrations significantly decreased following surgery. Therefore, the present results suggest that ADM, ANP and BNP may be involved in regulating adrenal medulla functions. PMID:27446289

  18. Near-infrared spectroscopic survey of B-type asteroids: compositional analysis

    NASA Astrophysics Data System (ADS)

    de Leon, J.; Pinilla-Alonso, N.; Licandro, J.; Campins, H.; Marzo, G. A.

    2011-10-01

    We present near-infrared spectra of 23 B-type asteroids obtained with the NICS cameraspectrograph at the 3.56 m Telescopio Nazionale Galileo. We also include visible and near-infrared spectra of 20 additional B-type asteroids from the literature, including near-Earth asteroid 1999 RQ36, primary target of NASA's OSIRIS-Rex sample return mission. A plot of the spectra of all the asteroids shows a continuous trend in the nearinfrared between red and blue slopes. We apply a clustering technique to reduce the volume of data to six "average spectra" or "centroids" representative of the whole sample. These spectra are then compared against the entire RELAB database to search for best analogs.

  19. PROJECTED ROTATIONAL VELOCITIES OF 136 EARLY B-TYPE STARS IN THE OUTER GALACTIC DISK

    SciTech Connect

    Garmany, C. D.; Glaspey, J. W.; Bragança, G. A.; Daflon, S.; Fernandes, M. Borges; Cunha, K.; Oey, M. S.; Bensby, T.

    2015-08-15

    We have determined projected rotational velocities, v sin i, from Magellan/MIKE echelle spectra for a sample of 136 early B-type stars having large Galactocentric distances. The target selection was done independently of their possible membership in clusters, associations or field stars. We subsequently examined the literature and assigned each star as Field, Association, or Cluster. Our v sin i results are consistent with a difference in aggregate v sin i with stellar density. We fit bimodal Maxwellian distributions to the Field, Association, and Cluster subsamples representing sharp-lined and broad-lined components. The first two distributions, in particular, for the Field and Association are consistent with strong bimodality in v sin i. Radial velocities are also presented, which are useful for further studies of binarity in B-type stars, and we also identify a sample of possible new double-lined spectroscopic binaries. In addition, we find 18 candidate Be stars showing emission at Hα.

  20. Spectroscopic Evidence for an Oxazolone Structure in Anionic b-Type Peptide Fragments

    NASA Astrophysics Data System (ADS)

    Grzetic, Josipa; Oomens, Jos

    2012-02-01

    Infrared spectra of anionic b-type fragments generated by collision induced dissociation (CID) from deprotonated peptides are reported. Spectra of the b2 fragments of deprotonated AlaAlaAla and AlaTyrAla have been recorded over the 800-1800 cm-1 spectral range by multiple-photon dissociation (MPD) spectroscopy using an FTICR mass spectrometer in combination with the free electron laser FELIX. Structural characterization of the b-type fragments is accomplished by comparison with density functional theory calculated spectra at the B3LYP/6-31++G(d,p) level for different isomeric structures. Although diketopiperazine structures represent the energetically lowest isomers, the IR spectra suggest an oxazolone structure for the b2 fragments of both peptides. Deprotonation is shown to occur on the oxazolone α-carbon, which leads to a conjugated structure in which the negative charge is practically delocalized over the entire oxazolone ring, providing enhanced gas-phase stability.

  1. The VLT-FLAMES Tarantula Survey. XXII. Multiplicity properties of the B-type stars

    NASA Astrophysics Data System (ADS)

    Dunstall, P. R.; Dufton, P. L.; Sana, H.; Evans, C. J.; Howarth, I. D.; Simón-Díaz, S.; de Mink, S. E.; Langer, N.; Maíz Apellániz, J.; Taylor, W. D.

    2015-08-01

    We investigate the multiplicity properties of 408 B-type stars observed in the 30 Doradus region of the Large Magellanic Cloud with multi-epoch spectroscopy from the VLT-FLAMES Tarantula Survey (VFTS). We use a cross-correlation method to estimate relative radial velocities from the helium and metal absorption lines for each of our targets. Objects with significant radial-velocity variations (and with an amplitude larger than 16 km s-1) are classified as spectroscopic binaries. We find an observed spectroscopic binary fraction (defined by periods of <103.5 d and mass ratios >0.1) for the B-type stars, fB(obs) = 0.25 ± 0.02, which appears constant across the field of view, except for the two older clusters (Hodge 301 and SL 639). These two clusters have significantly lower binary fractions of 0.08 ± 0.08 and 0.10 ± 0.09, respectively. Using synthetic populations and a model of our observed epochs and their potential biases, we constrain the intrinsic multiplicity properties of the dwarf and giant (i.e. relatively unevolved) B-type stars in 30 Dor. We obtain a present-day binary fraction fB(true) = 0.58 ± 0.11, with a flat period distribution. Within the uncertainties, the multiplicity properties of the B-type stars agree with those for the O stars in 30 Dor from the VFTS. Appendices A, B are available in electronic form at http://www.aanda.orgFull Tables 2 and 3 are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/580/A93

  2. An Einstein Observatory SAO-based catalog of B-type stars

    NASA Technical Reports Server (NTRS)

    Grillo, F.; Sciortino, S.; Micela, G.; Vaiana, G. S.; Harnden, F. R., Jr.

    1992-01-01

    About 4000 X-ray images obtained with the Einstein Observatory are used to measure the 0.16-4.0 keV emission from 1545 B-type SAO stars falling in the about 10 percent of the sky surveyed with the IPC. Seventy-four detected X-ray sources with B-type stars are identified, and it is estimated that no more than 15 can be misidentified. Upper limits to the X-ray emission of the remaining stars are presented. In addition to summarizing the X-ray measurements and giving other relevant optical data, the present extensive catalog discusses the reduction process and analyzes selection effects associated with both SAO catalog completeness and IPC target selection procedures. It is concluded that X-ray emission, at the level of Lx not less than 10 exp 30 ergs/s, is quite common in B stars of early spectral types (B0-B3), regardless of luminosity class, but that emission, at the same level, becomes less common, or nonexistent, in later B-type stars.

  3. Effect of atrial natriuretic peptide on potassium-stimulated aldosterone secretion: potential relevance to hypoaldosteronism in man.

    PubMed

    Clark, B A; Brown, R S; Epstein, F H

    1992-08-01

    Atrial natriuretic peptide (ANP) has been shown to suppress aldosterone secretion under certain circumstances, although the physiological significance of this is uncertain. We wondered if ANP would suppress potassium-stimulated aldosterone secretion in man and, if so, whether we might find high circulating levels of ANP in patients with the syndrome of acquired hypoaldosteronism. We studied seven healthy young subjects under two conditions: 1) infusion of KCl (0.5 mmol/kg) over 45 min, and 2) KCl infused with ANP (0.01 microgram/kg.min) for 60 min. We also evaluated ANP levels in eight elderly subjects with the syndrome of acquired hypoaldosteronism, as defined by hyperkalemia (mean serum K+, 5.3 +/- 0.1 mmol/L) associated with inappropriately low aldosterone levels (216 +/- 50 pmol/L). In the normal subjects, ANP almost completely suppressed the aldosterone response to KCl infusion (P less than 0.001, by analysis of variance) despite a similar rise in the serum potassium level with KCl alone (0.70 +/- 0.07 mmol/L) and KCl plus ANP (0.75 +/- 0.09 mmol/L). PRA fell slightly during KCl plus ANP treatment, but did not change during the infusion of KCl alone. ANP levels were approximately 800 pmol/L during the ANP infusion studies. Endogenous ANP levels in the hyperkalemic patients with hypoaldosteronism were markedly elevated at 1186 +/- 340 pmol/L (compared to 93 +/- 10 pmol/L in healthy elderly controls), a level that would be capable of suppressing the potassium-mediated aldosterone response. Exogenous infusion of ANP suppressed the aldosterone response to hyperkalemia, and ANP levels were found to be markedly elevated in a group of patients with hyperkalemia and hypoaldosteronism. We suggest that ANP may contribute to clinically significant hypoaldosteronism and hyperkalemia in the syndrome of acquired hypoaldosteronism.

  4. VizieR Online Data Catalog: Spectrocopic Binarity of O and B type stars (Chini+, 2012)

    NASA Astrophysics Data System (ADS)

    Chini, R.; Hoffmeister, V. H.; Nasseri, A.; Stahl, O.; Zinnecker, H.

    2013-05-01

    We have performed a comprehensive spectroscopic survey on a large representative sample of 249 O- and 581 B-type stars. Using the high-resolution spectrograph BESO at the Hexapod Telescope at the Universitatssternwarte Bochum near Cerro Armazones in Chile, we obtained 3632 multi-epoch optical spectra. The observing period started in 2009 January and is still going on. The spectra comprise a wavelength range from 3620 to 8530Å and provide a mean spectral resolution of R=50000. (1 data file).

  5. MASS AND DENSITY OF THE B-TYPE ASTEROID (702) ALAUDA

    SciTech Connect

    Rojo, P.; Margot, J. L. E-mail: jlm@astro.ucla.edu

    2011-02-01

    Observations with the adaptive optics system on the Very Large Telescope reveal that the outer main belt asteroid (702) Alauda has a small satellite with primary to secondary diameter ratio of {approx}56. The secondary revolves around the primary in 4.9143 {+-} 0.007 days at a distance of 1227 {+-} 24 km, yielding a total system mass of (6.057 {+-} 0.36) x 10{sup 18} kg. Combined with an IRAS size measurement, our data yield a bulk density of 1570 {+-} 500 kg m{sup -3} for this B-type asteroid.

  6. 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

  7. Improving Stellar Parameter and Abundance Determinations of Early B-Type Stars

    NASA Astrophysics Data System (ADS)

    Nieva, M.-F.; Przybilla, N.

    2010-06-01

    In the past years we have made great efforts to reduce the statistical and systematic uncertainties in stellar parameter and chemical abundance determinations of early B-type stars. Both the construction of robust model atoms for non-LTE line-formation calculations and a novel self-consistent spectral analysis methodology were decisive to achieve results of unprecedented precision. They were extensively tested and applied to high-quality spectra of stars from OB associations and the field in the solar neighborhood, covering a broad parameter range. Initially, most lines of hydrogen, helium and carbon in the optical/near-IR spectral range were reproduced simultaneously in a consistent way for the first time, improving drastically on the accuracy of results in published work. By taking additional ionization equilibria of oxygen, neon, silicon, and iron into account, uncertainties as low as ˜1% in effective temperature, ˜10% in surface gravity and ˜20% in elemental abundances are achieved—compared to ˜5-10%, ˜25% and a factor ˜2-3 using standard methods. Several sources of systematic errors have been identified by comparison of our analysis methods for early B-type stars with previously used standard techniques, e.g., the VLT-FLAMES survey of massive stars. Improvements in automatic analyses are strongly recommended for meaningful comparisons of spectroscopic stellar parameters and chemical abundances (“observational constraints”) with predictions of stellar and galactic chemical evolution models.

  8. Formation of Nonclassical Ordered Phases of A B -Type Multiarm Block Copolymers

    NASA Astrophysics Data System (ADS)

    Gao, Ya; Deng, Hanlin; Li, Weihua; Qiu, Feng; Shi, An-Chang

    2016-02-01

    The formation of ordered phases from block copolymers is driven by a delicate balance between the monomer-monomer interaction and chain configurational entropy. The configurational entropy can be regulated by designed chain architecture, resulting in a new entropy-driven mechanism to control the self-assembly of ordered phases from block copolymers. An effective routine to regulate the configurational entropy is to utilize multiarm architecture, in which the entropic contribution to the free energy could be qualitatively controlled by the fraction of bridging configurations. As an illustration of this mechanism, the phase behavior of two A B -type multiarm block copolymers, B0-(Bi-Ai) m and (B1-Ai-B2) m where the minority A blocks form cylindrical or spherical domains, are examined using the self-consistent field theory (SCFT). The SCFT results demonstrate that the packing symmetry of the cylinders or spheres can be controlled by the length of the bridging B blocks. Several nonclassical ordered phases, including a novel square array cylinder with p 4 m m symmetry, are predicted to form from the A B -type multiarm block copolymers.

  9. Identification of a major QTL controlling the content of B-type starch granules in Aegilops

    PubMed Central

    Howard, Thomas; Rejab, Nur Ardiyana; Griffiths, Simon; Leigh, Fiona; Leverington-Waite, Michelle; Simmonds, James; Uauy, Cristobal; Trafford, Kay

    2011-01-01

    Starch within the endosperm of most species of the Triticeae has a unique bimodal granule morphology comprising large lenticular A-type granules and smaller near-spherical B-type granules. However, a few wild wheat species (Aegilops) are known to lack B-granules. Ae. peregrina and a synthetic tetraploid Aegilops with the same genome composition (SU) were found to differ in B-granule number. The synthetic tetraploid had normal A- and B-type starch granules whilst Ae. peregrina had only A-granules because the B-granules failed to initiate. A population segregating for B-granule number was generated by crossing these two accessions and was used to study the genetic basis of B-granule initiation. A combination of Bulked Segregant Analysis and QTL mapping identified a major QTL located on the short arm of chromosome 4S that accounted for 44.4% of the phenotypic variation. The lack of B-granules in polyploid Aegilops with diverse genomes suggests that the B-granule locus has been lost several times independently during the evolution of the Triticeae. It is proposed that the B-granule locus is susceptible to silencing during polyploidization and a model is presented to explain the observed data based on the assumption that the initiation of B-granules is controlled by a single major locus per haploid genome. PMID:21227932

  10. [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

  11. Spectropolarimetry of B-type and C-type asteroids: Phase Curves and Wavelength Dependence

    NASA Astrophysics Data System (ADS)

    Maleszewski, C.; McMillan, R. S.; Smith, P. S.

    2014-12-01

    We present recent spectropolarimetric observations of eleven B- and C-type asteroids using SPOL (http://james.as.arizona.edu/~psmith/SPOL/) at the 2.3-m Bok and 1.6-m Kuiper telescopes. Our primary goal is to further constrain our understanding of the wavelength dependence of linear polarization. For each object, we produced polarimetric phase curves (linear polarization vs. phase angle) and measure the wavelength dependence in each observation by calculating the slope of each polarization spectrum. Previous analysis by Belskaya et al. (2009) shows that the slope of the polarization spectrum increases as the wavelength increases. No analysis of the wavelength dependence in B-types has occurred previously to our knowledge. For the five C-type (3 Ch- and 2 C-) objects observed, those of the Ch-type have larger minimum polarizations than of the C- subtype. This is consistent with polarimetric phase curves of similar asteroids by Gil-Hutton and Cañada-Assandri (2012). With respect to the wavelength dependence, our observed targets show an increase in polarization slope with wavelength, confirming the Belskaya (2009) result. After dividing the data by group, C- subtype objects have relatively flat polarization spectra, as opposed to the Ch- subtypes that have more rapidly changing slopes as phase angle increases. A mineralogical basis for the variety of wavelength dependences observed is most likely. Additional observations of the other C- subtypes will aid to distinguish how mineralogical variation affects polarization. It may also explain the wide range of polarization slopes measured near a phase angle of ten degrees in the Belskaya (2009) analysis. Six B-type asteroids were observed in a similar manner. As with the C-types, the polarimetric phase curves vary in shape, suggesting differences in albedo. Also, the wavelength dependence increases with wavelength, as shown for the C-types. On the other hand, all of the B-type objects have a similar wavelength dependence

  12. Plasma atrial natriuretic peptide after the Fontan procedure and total cavopulmonary connexion.

    PubMed

    Burch, M; Shinebourne, E A; Rigby, M L; Carter, N; Jeffery, S; Stanley, P; Smith, A

    1990-05-01

    Plasma atrial natriuretic peptide was measured in 10 children undergoing the Fontan procedure and 3 children undergoing total cavopulmonary connexion. There was no significant difference in pre-operative plasma levels, but post-operative levels were significantly higher 48 hours after cardiopulmonary bypass in the Fontan group. There was no significant difference in plasma arginine vasopressin levels either pre- or post-operatively. Post-operative pleural effusions occurred in only 2 of the 10 patients undergoing the Fontan procedure, but were present in all 3 of those undergoing total cavopulmonary connexion. The release of atrial natriuretic peptide is an appropriate homeostatic response to volume loading and the impairment of this response in the early post-operative period may be of clinical importance.

  13. Quantitative proteome changes in Arabidopsis thaliana suspension-cultured cells in response to plant natriuretic peptides.

    PubMed

    Turek, Ilona; Wheeler, Janet I; Gehring, Chris; Irving, Helen R; Marondedze, Claudius

    2015-09-01

    Proteome changes in the Arabidopsis thaliana suspension cells in response to the A. thaliana plant natriuretic peptide (PNP), AtPNP-A (At2g18660) were assessed using quantitative proteomics employing tandem mass tag (TMT) labeling and tandem mass spectrometry (LC-MS/MS). In this study, we characterized temporal responses of suspension-cultured cells to 1 nM and 10 pM AtPNP-A at 0, 10 and 30 min post-treatment. Both concentrations we found to yield a distinct differential proteome signature. The data shown in this article are associated with the article "Plant natriuretic peptides induce a specific set of proteins diagnostic for an adaptive response to abiotic stress" by Turek et al. (Front. Plant Sci. 5 (2014) 661) and have been deposited to the ProteomeXchange with identifier PXD001386. PMID:26217812

  14. Cardiac content of brain natriuretic peptide in DOCA-salt hypertensive rats

    SciTech Connect

    Yokota, Naoto; Aburaya, Masahito; Yamamoto, Yoshitaka; Kato, Johji; Kitamura, Kazuo; Kida, Osamu; Eto, Tanenao; Kangawa, Kenji; Tanaka, Kenjiro ); Minamino, Naoto; Matsuo, Hisayuki )

    1991-01-01

    The cardiac content of immunoreactive rat brain natriuretic peptide (ir-rBNP) in deoxycorticosterone acetate (DOCA)-salt hypertensive rats was measured by radioimmunoassay (RIA). The atrial content of ir-rBNP was significantly lower in the DOCA-salt group than in the control group. However, the ventricular content of ir-rBNP was markedly increased in the DOCA-salt group as compared to the other groups. Ir-rBNP level in the atria was negatively correlated with blood pressure, while that in the ventricle was positively correlated with blood pressure. A significant correlation was observed between tissue levels of ir-rBNP and ir-rat atrial natriuretic peptide (rANP) both in atrium and ventricle. These results raise the possibility that rBNP as well as rANP functions as a cardiac hormone, the production of which probably changes in response to increased of body fluid and blood pressure.

  15. Atrial natriuretic factor inhibits mitogen-induced growth in aortic smooth muscle cells.

    PubMed

    Baldini, P M; De Vito, P; Fraziano, M; Mattioli, P; Luly, P; Di Nardo, P

    2002-10-01

    Atrial natriuretic factor (ANF) is a polypeptide able to affect cardiovascular homeostasis exhibiting diuretic, natriuretic, and vasorelaxant activities. ANF shows antimitogenic effects in different cell types acting through R(2) receptor. Excessive proliferation of smooth muscle cells is a common phenomenon in diseases such as atherosclerosis, but the role of growth factors in the mechanism which modulate this process has yet to be clarified. The potential antimitogenic role of ANF on the cell growth induced by growth factors appears very intriguing. Aim of the present study was to investigate the possible involvement of ANF on rat aortic smooth muscle (RASM) cells proliferation induced by known mitogens and the mechanism involved. Our data show that ANF, at physiological concentration range, inhibits RASM cell proliferation induced by known mitogens such as PDGF and insulin, and the effect seems to be elicited through the modulation of phosphatidic acid (PA) production and MAP kinases involvement.

  16. C-type natriuretic peptide plasma levels are reduced in obese adolescents.

    PubMed

    Del Ry, S; Cabiati, M; Bianchi, V; Storti, S; Caselli, C; Prescimone, T; Clerico, A; Saggese, G; Giannessi, D; Federico, G

    2013-12-01

    The high prevalence of obesity in children may increase the magnitude of lifetime risk of cardiovascular disease (CD). At present, explicit data for recommending biomarkers as routine pre-clinical markers of CD in children are lacking. C-type natriuretic peptide (CNP) is assuming increasing importance in CD; in adults with heart failure, its plasma levels are related to clinical and functional disease severity. We have previously reported five different reference intervals for blood CNP as a function of age in healthy children; however, data on plasma CNP levels in obese children are still lacking. Aim of this study was to assess CNP levels in obese adolescents and verify whether they differ from healthy subjects. Plasma CNP was measured in 29 obese adolescents (age: 11.8 ± 0.4 years; BMI: 29.8 ± 0.82) by radioimmunoassay and compared with the reference values of healthy subjects. BNP was also measured. Both plasma CNP and BNP levels were significantly lower in the obese adolescents compared to the appropriate reference values (CNP: 3.4 ± 0.2 vs 13.6 ± 2.3 pg/ml, p<0.0001; BNP: 18.8 ± 2.6 vs 36.9 ± 5.5 pg/ml, p=0.003). There was no significant difference between CNP values in males and females. As reported in adults, we observed lower plasma CNP and BNP levels in obese children, suggesting a defective natriuretic peptide system in these patients. An altered regulation of production, clearance and function of natriuretic peptides, already operating in obese adolescents, may possibly contribute to the future development of CD. Thus, the availability of drugs promoting the action of natriuretic peptides may represent an attractive therapeutic option to prevent CD.

  17. Pseudomonas aeruginosa Expresses a Functional Human Natriuretic Peptide Receptor Ortholog: Involvement in Biofilm Formation

    PubMed Central

    Rosay, Thibaut; Bazire, Alexis; Diaz, Suraya; Clamens, Thomas; Blier, Anne-Sophie; Mijouin, Lily; Hoffmann, Brice; Sergent, Jacques-Aurélien; Bouffartigues, Emeline; Boireau, Wilfrid; Vieillard, Julien; Hulen, Christian; Dufour, Alain; Harmer, Nicholas J.; Feuilloley, Marc G. J.

    2015-01-01

    ABSTRACT Considerable evidence exists that bacteria detect eukaryotic communication molecules and modify their virulence accordingly. In previous studies, it has been demonstrated that the increasingly antibiotic-resistant pathogen Pseudomonas aeruginosa can detect the human hormones brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) at micromolar concentrations. In response, the bacterium modifies its behavior to adapt to the host physiology, increasing its overall virulence. The possibility of identifying the bacterial sensor for these hormones and interfering with this sensing mechanism offers an exciting opportunity to directly affect the infection process. Here, we show that BNP and CNP strongly decrease P. aeruginosa biofilm formation. Isatin, an antagonist of human natriuretic peptide receptors (NPR), prevents this effect. Furthermore, the human NPR-C receptor agonist cANF4-23 mimics the effects of natriuretic peptides on P. aeruginosa, while sANP, the NPR-A receptor agonist, appears to be weakly active. We show in silico that NPR-C, a preferential CNP receptor, and the P. aeruginosa protein AmiC have similar three-dimensional (3D) structures and that both CNP and isatin bind to AmiC. We demonstrate that CNP acts as an AmiC agonist, enhancing the expression of the ami operon in P. aeruginosa. Binding of CNP and NPR-C agonists to AmiC was confirmed by microscale thermophoresis. Finally, using an amiC mutant strain, we demonstrated that AmiC is essential for CNP effects on biofilm formation. In conclusion, the AmiC bacterial sensor possesses structural and pharmacological profiles similar to those of the human NPR-C receptor and appears to be a bacterial receptor for human hormones that enables P. aeruginosa to modulate biofilm expression. PMID:26307165

  18. Protective effect of lyophilized recombinant human brain natriuretic peptide on renal ischemia/reperfusion injury in mice.

    PubMed

    Cao, X; Xia, H Y; Zhang, T; Qi, L C; Zhang, B Y; Cui, R; Chen, X; Zhao, Y R; Li, X Q

    2015-10-27

    Brain natriuretic peptide (BNP) has a protective effect on acute injury of the heart, brain, and lung. However, its role in acute kidney injury (AKI) remains unclear. The aim of this study was to investigate the effect of lyophilized recombinant human BNP (lrh-BNP) on AKI and the underlying molecular mechanisms. An experimental model for AKI was established using an ischemia/reperfusion (I/R) procedure. Healthy adult BALB/c mice were randomized to the sham, I/R, and lrh-BNP-treated post-I/R (BNP + I/R) groups. Post-operatively, the BNP + I/R group was subcutaneously injected with lrh-BNP (0.03 μg·kg(-1)·min(-1)), whereas the other groups received saline at the same dose. Serum creatinine (Scr) and blood urea nitrogen levels were examined; tissue staining was performed to evaluate the degree of I/R injury (IRI). Ki67 positive staining of renal tubular epithelial cells was observed using immunofluorescence confocal laser scanning to assess the effect of BNP on cell proliferation after IRI. Inflammatory factor expression levels were detected to evaluate the effect of BNP on renal inflammation. Compared with the sham group, the I/R group showed increased Scr levels, severe tubular injury of the renal outer medulla, increased Kim-1 mRNA expression, an increased number of infiltrative macrophages in the renal interstitium, and increased TNF-α, IL- 1β, IL-6, MCP-1, and HIF-1α mRNA expression. BNP delivery significantly reduced all pathological changes in the I/R group. The protective role of BNP in murine renal IRI may be associated with its inhibition of renal interstitial inflammation and hypoxia and its promotion of renal tubule repair.

  19. The Lyman-Continuum Fluxes and Stellar Parameters of O and Early B-Type Stars

    NASA Technical Reports Server (NTRS)

    Vacca, William D.; Garmany, Catherine D.; Shull, J. Michael

    1996-01-01

    Using the results of the most recent stellar atmosphere models applied to a sample of hot stars, we construct calibrations of effective temperature (T(sub eff)), and gravity (log(sub g)) with a spectral type and luminosity class for Galactic 0-type and early B-type stars. From the model results we also derive an empirical relation between the bolometric correction and T(sub eff) and log g. Using a sample of stars with known distances located in OB associations in the Galaxy and the Large Magellanic Cloud, we derive a new calibration of M(sub v) with spectral class. With these new calibrations and the stellar atmosphere models of Kurucz, we calculate the physical parameters and ionizing photon luminosities in the H(0) and He(0) continua for O and early B-type stars. We find substantial differences between our values of the Lyman- continuum luminosity and those reported in the literature. We also discuss the systematic discrepancy between O-type stellar masses derived from spectroscopic models and those derived from evolutionary tracks. Most likely, the cause of this 'mass discrepancy' lies primarily in the atmospheric models, which are plane parallel and hydrostatic and therefore do not account for an extended atmosphere and the velocity fields in a stellar wind. Finally, we present a new computation of the Lyman-continuum luminosity from 429 known O stars located within 2.5 kpc of the Sun. We find the total ionizing luminosity from this population ((Q(sub 0)(sup T(sub ot))) = 7.0 x 10(exp 51) photons/s) to be 47% larger than that determined using the Lyman continuum values tabulated by Panagia.

  20. Pharmacological chaperones as a potential therapeutic option in methylmalonic aciduria cblB type

    PubMed Central

    Jorge-Finnigan, Ana; Brasil, Sandra; Underhaug, Jarl; Ruíz-Sala, Pedro; Merinero, Begoña; Banerjee, Ruma; Desviat, Lourdes R.; Ugarte, Magdalena; Martinez, Aurora; Pérez, Belén

    2013-01-01

    Methylmalonic aciduria (MMA) cblB type is caused by mutations in the MMAB gene. This encodes the enzyme ATP:cob(I)alamin adenosyltransferase (ATR), which converts reduced cob(I)alamin to an active adenosylcobalamin cofactor. We recently reported the presence of destabilizing pathogenic mutations that retain some residual ATR activity. The aim of the present study was to seek pharmacological chaperones as a tailored therapy for stabilizing the ATR protein. High-throughput ligand screening of over 2000 compounds was performed; six were found to enhance the thermal stability of purified recombinant ATR. Further studies using a well-established bacterial system in which the recombinant ATR protein was expressed in the presence of these six compounds, showed them all to increase the stability of the wild-type ATR and the p.Ile96Thr mutant proteins. Compound V (N-{[(4-chlorophenyl)carbamothioyl]amino}-2-phenylacetamide) significantly increased this stability and did not act as an inhibitor of the purified protein. Importantly, compound V increased the activity of ATR in patient-derived fibroblasts harboring the destabilizing p.Ile96Thr mutation in a hemizygous state to within control range. When cobalamin was coadministrated with compound V, mutant ATR activity further improved. Oral administration of low doses of compound V to C57BL/6J mice for 12 days, led to increase in steady-state levels of ATR protein in liver and brain (disease-relevant organs). These results hold promise for the clinical use of pharmacological chaperones in MMA cblB type patients harboring chaperone-responsive mutations. PMID:23674520

  1. 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

  2. Demonstration of natriuretic activity in urine of neurosurgical patients with renal salt wasting

    PubMed Central

    Youmans, Steven J; Fein, Miriam R; Wirkowski, Elizabeth; Maesaka, John K

    2013-01-01

    We have utilized the persistent elevation of fractional excretion (FE) of urate, > 10%, to differentiate cerebral/renal salt wasting (RSW) from the syndrome of inappropriate antidiuretic hormone secretion (SIADH), in which a normalization of FEurate occurs after correction of hyponatremia.  Previous studies suggest as well  that an elevated FEurate with normonatremia, without pre-existing hyponatremia, is also consistent with RSW, including studies demonstrating induction of RSW in rats infused with plasma from normonatremic neurosurgical and Alzheimer’s disease patients.  The present studies were designed to test whether precipitates from the urine of normonatremic neurosurgical patients, with either normal or elevated FEurate, and patients with SIADH, display natriuretic activity.   Methods: Ammonium sulfate precipitates from the urine of 6 RSW and 5 non-RSW Control patients were dialyzed (10 kDa cutoff) to remove the ammonium sulfate, lyophilized, and the reconstituted precipitate was tested for its effect on transcellular transport of 22Na across LLC-PK1 cells grown to confluency in transwells. Results: Precipitates from 5 of the 6 patients with elevated FEurate and normonatremia significantly inhibited the in vitro transcellular transport of 22Na above a concentration of 3 μg protein/ml, by 10-25%, versus to vehicle alone, and by 15-40% at concentrations of 5-20 μg/ml as compared to precipitates from 4 of the 5 non-RSW patients with either normal FEurate and normonatremia (2 patients) or with SIADH (2 patients). Conclusion: These studies provide further evidence that an elevated FEurate with normonatremia is highly consistent with RSW.  Evidence in the urine of natriuretic activity suggests significant renal excretion of the natriuretic factor. The potentially large source of the natriuretic factor that this could afford, coupled with small analytical sample sizes required by the in-vitro bioassay used here, should facilitate future experimental

  3. 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

  4. PULSATING B-TYPE STARS IN THE OPEN CLUSTER NGC 884: FREQUENCIES, MODE IDENTIFICATION, AND ASTEROSEISMOLOGY

    SciTech Connect

    Saesen, S.; Briquet, M.; Aerts, C.; Carrier, F.; Miglio, A.

    2013-10-01

    Recent progress in the seismic interpretation of field β Cep stars has resulted in improvements of the physical description in the stellar structure and evolution model computations of massive stars. Further asteroseismic constraints can be obtained from studying ensembles of stars in a young open cluster, which all have similar age, distance, and chemical composition. We present an observational asteroseismology study based on the discovery of numerous multi-periodic and mono-periodic B stars in the open cluster NGC 884. We describe a thorough investigation of the pulsational properties of all B-type stars in the cluster. Overall, our detailed frequency analysis resulted in 115 detected frequencies in 65 stars. We found 36 mono-periodic, 16 bi-periodic, 10 tri-periodic, and 2 quadru-periodic stars and one star with nine independent frequencies. We also derived the amplitudes and phases of all detected frequencies in the U, B, V, and I filter, if available. We achieved unambiguous identifications of the mode degree for 12 of the detected frequencies in nine of the pulsators. Imposing the identified degrees and measured frequencies of the radial, dipole, and quadrupole modes of five pulsators led to a seismic cluster age estimate of log (age/yr) = 7.12-7.28 from a comparison with stellar models. Our study is a proof-of-concept for and illustrates the current status of ensemble asteroseismology of a young open cluster.

  5. Facile synthesis of B-type carbonated nanoapatite with tailored microstructure

    NASA Astrophysics Data System (ADS)

    Gualtieri, Magdalena Lassinantti; Romagnoli, Marcello; Hanuskova, Miriam; Fabbri, Elena; Gualtieri, Alessandro F.

    2014-12-01

    Nanolime and a phosphate-based chelating agent were used to synthesize B-type carbonated apatite. Developed Rietveld refinement strategies allowed one to determine process yield, product crystallinity as well as structural (unit cell) and microstructural (size, strain) parameters. The effect of synthesis temperature (20-60 °C) as well as Ca/P ratio (1.5-2.5) and solid content (10-30 wt%) of the starting batch on these properties were investigated. FTIR, TEM and gas adsorption data provided supporting evidence. The process yield was 42-60 wt% and found to be governed by the Ca/P ratio. The purified products had high specific surface area (107-186 m2/g) and crystallinity (76-97%). The unit cell parameters, correlated to the degree of structural carbonate, were sensitive to the Ca/P ratio. Instead, temperature governed the microstructural parameters. Less strained and larger crystals were obtained at higher temperatures. Long-term aging up to 6 months at 20 °C compensated for higher crystal growth kinetics at higher temperature.

  6. Identification of B-type procyanidins in Fallopia spp. involved in biological denitrification inhibition.

    PubMed

    Bardon, Clément; Piola, Florence; Haichar, Feth el Zahar; Meiffren, Guillaume; Comte, Gilles; Missery, Boris; Balby, Manon; Poly, Franck

    2016-02-01

    Nitrogen (N) is considered as a main limiting factor in plant growth, and nitrogen losses through denitrification can be responsible for severe decreases in plant productivity. Recently, it was demonstrated that Fallopia spp. is responsible for biological denitrification inhibition (BDI) through the release of unknown secondary metabolites. Here, we investigate the secondary metabolites involved in the BDI of Fallopia spp. The antioxidant, protein precipitation capability of Fallopia spp. extracts was measured in relation to the aerobic respiration and denitrification of two bacteria (Gram positive and Gram negative). Proanthocyanidin concentrations were estimated. Proanthocyanidins in extracts were characterized by chromatographic analysis, purified and tested on the bacterial denitrification and aerobic respiration of two bacterial strains. The effect of commercial procyanidins on denitrification was tested on two different soil types. Denitrification and aerobic respiration inhibition were correlated with protein precipitation capacity and concentration of proanthocyanidins but not to antioxidant capacity. These proanthocyanidins were B-type procyanidins that inhibited denitrification more than the aerobic respiration of bacteria. In addition, procyanidins also inhibited soil microbial denitrification. We demonstrate that procyanidins are involved in the BDI of Fallopia spp. Our results pave the way to a better understanding of plant-microbe interactions and highlight future applications for a more sustainable agriculture.

  7. Endothelial Expression of Scavenger Receptor Class B, Type I Protects against Development of Atherosclerosis in Mice

    PubMed Central

    Vaisman, Boris L.; Vishnyakova, Tatyana G.; Freeman, Lita A.; Amar, Marcelo J.; Demosky, Stephen J.; Liu, Chengyu; Stonik, John A.; Sampson, Maureen L.; Pryor, Milton; Bocharov, Alexander V.; Eggerman, Thomas L.; Patterson, Amy P.; Remaley, Alan T.

    2015-01-01

    The role of scavenger receptor class B, type I (SR-BI) in endothelial cells (EC) was examined in several novel transgenic mouse models expressing SR-BI in endothelium of mice with normal C57Bl6/N, apoE-KO, or Scarb1-KO backgrounds. Mice were also created expressing SR-BI exclusively in endothelium and liver. Endothelial expression of the Tie2-Scarb1 transgene had no significant effect on plasma lipoprotein levels in mice on a normal chow diet but on an atherogenic diet, significantly decreased plasma cholesterol levels, increased plasma HDL cholesterol (HDL-C) levels, and protected mice against atherosclerosis. In 8-month-old apoE-KO mice fed a normal chow diet, the Tie2-Scarb1 transgene decreased aortic lesions by 24%. Mice expressing SR-BI only in EC and liver had a 1.5 ± 0.1-fold increase in plasma cholesterol compared to mice synthesizing SR-BI only in liver. This elevation was due mostly to increased HDL-C. In EC culture studies, SR-BI was found to be present in both basolateral and apical membranes but greater cellular uptake of cholesterol from HDL was found in the basolateral compartment. In summary, enhanced expression of SR-BI in EC resulted in a less atherogenic lipoprotein profile and decreased atherosclerosis, suggesting a possible role for endothelial SR-BI in the flux of cholesterol across EC. PMID:26504816

  8. Emergent criticality in complex turing B-type atomic switch networks.

    PubMed

    Stieg, Adam Z; Avizienis, Audrius V; Sillin, Henry O; Martin-Olmos, Cristina; Aono, Masakazu; Gimzewski, James K

    2012-01-10

    Recent advances in the neuromorphic operation of atomic switches as individual synapse-like devices demonstrate the ability to process information with both short-term and long-term memorization in a single two terminal junction. Here it is shown that atomic switches can be self-assembled within a highly interconnected network of silver nanowires similar in structure to Turing’s “B-Type unorganized machine”, originally proposed as a randomly connected network of NAND logic gates. In these experimental embodiments,complex networks of coupled atomic switches exhibit emergent criticality similar in nature to previously reported electrical activity of biological brains and neuron assemblies. Rapid fluctuations in electrical conductance display metastability and power law scaling of temporal correlation lengths that are attributed to dynamic reorganization of the interconnected electro-ionic network resulting from induced non-equilibrium thermodynamic instabilities. These collective properties indicate a potential utility for realtime,multi-input processing of distributed sensory data through reservoir computation. We propose these highly coupled, nonlinear electronic networks as an implementable hardware-based platform toward the creation of physically intelligent machines. PMID:22329003

  9. Interferon alpha bioactivity critically depends on Scavenger receptor class B type I function.

    PubMed

    Vasquez, Marcos; Fioravanti, Jessica; Aranda, Fernando; Paredes, Vladimir; Gomar, Celia; Ardaiz, Nuria; Fernandez-Ruiz, Veronica; Méndez, Miriam; Nistal-Villan, Estanislao; Larrea, Esther; Gao, Qinshan; Gonzalez-Aseguinolaza, Gloria; Prieto, Jesus; Berraondo, Pedro

    2016-08-01

    Scavenger receptor class B type I (SR-B1) binds pathogen-associated molecular patterns participating in the regulation of the inflammatory reaction but there is no information regarding potential interactions between SR-B1 and the interferon system. Herein, we report that SR-B1 ligands strongly regulate the transcriptional response to interferon α (IFNα) and enhance its antiviral and antitumor activity. This effect was mediated by the activation of TLR2 and TLR4 as it was annulled by the addition of anti-TLR2 or anti-TLR4 blocking antibodies. In vivo, we maximized the antitumor activity of IFNα co-expressing in the liver a SR-B1 ligand and IFNα by adeno-associated viruses. This gene therapy strategy eradicated liver metastases from colon cancer with reduced toxicity. On the other hand, genetic and pharmacological inhibition of SR-B1 blocks the clathrin-dependent interferon receptor recycling pathway with a concomitant reduction in IFNα signaling and bioactivity. This effect can be applied to enhance cancer immunotherapy with oncolytic viruses. Indeed, SR-B1 antagonists facilitate replication of oncolytic viruses amplifying their tumoricidal potential. In conclusion, SR-B1 agonists behave as IFNα enhancers while SR-B1 inhibitors dampen IFNα activity. These results demonstrate that SR-B1 is a suitable pharmacology target to enhance cancer immunotherapy based on IFNα and oncolytic viruses. PMID:27622065

  10. Interferon alpha bioactivity critically depends on Scavenger receptor class B type I function

    PubMed Central

    Vasquez, Marcos; Fioravanti, Jessica; Aranda, Fernando; Paredes, Vladimir; Gomar, Celia; Ardaiz, Nuria; Fernandez-Ruiz, Veronica; Méndez, Miriam; Nistal-Villan, Estanislao; Larrea, Esther; Gao, Qinshan; Gonzalez-Aseguinolaza, Gloria; Prieto, Jesus; Berraondo, Pedro

    2016-01-01

    ABSTRACT Scavenger receptor class B type I (SR-B1) binds pathogen-associated molecular patterns participating in the regulation of the inflammatory reaction but there is no information regarding potential interactions between SR-B1 and the interferon system. Herein, we report that SR-B1 ligands strongly regulate the transcriptional response to interferon α (IFNα) and enhance its antiviral and antitumor activity. This effect was mediated by the activation of TLR2 and TLR4 as it was annulled by the addition of anti-TLR2 or anti-TLR4 blocking antibodies. In vivo, we maximized the antitumor activity of IFNα co-expressing in the liver a SR-B1 ligand and IFNα by adeno-associated viruses. This gene therapy strategy eradicated liver metastases from colon cancer with reduced toxicity. On the other hand, genetic and pharmacological inhibition of SR-B1 blocks the clathrin-dependent interferon receptor recycling pathway with a concomitant reduction in IFNα signaling and bioactivity. This effect can be applied to enhance cancer immunotherapy with oncolytic viruses. Indeed, SR-B1 antagonists facilitate replication of oncolytic viruses amplifying their tumoricidal potential. In conclusion, SR-B1 agonists behave as IFNα enhancers while SR-B1 inhibitors dampen IFNα activity. These results demonstrate that SR-B1 is a suitable pharmacology target to enhance cancer immunotherapy based on IFNα and oncolytic viruses. PMID:27622065

  11. Identification of a hemerythrin-like domain in a P1B-type transport ATPase†

    PubMed Central

    Traverso, Matthew E.; Subramanian, Poorna; Davydov, Roman; Hoffman, Brian M.; Stemmler, Timothy L.; Rosenzweig, Amy C.

    2010-01-01

    The P1B-type ATPases couple the energy of ATP hydrolysis to metal ion translocation across cell membranes. Important for prokaryotic metal resistance and essential metal distribution in eukaryotes, P1B-ATPases are divided into subclasses on the basis of their metal substrate specificities. Sequence analysis of putative P1B-5-ATPases, for which the substrate has not been identified, led to the discovery of a C-terminal soluble domain homologous to hemerythrin (Hr) proteins and domains. The Hr domain from the Acidothermus cellulolyticus P1B-5-ATPase was cloned, expressed, and purified (P1B-5-Hr). P1B-5-Hr binds two iron ions per monomer and adopts a predominantly helical fold. Optical absorption features of the iron-loaded and azide-treated protein are consistent with features observed for other Hr proteins. Autooxidation to the met form is very rapid, as reported for other prokaryotic Hr domains. The presence of a diiron center was confirmed by electron paramagnetic resonance (EPR) and X-ray absorption spectroscopic (XAS) data. The occurrence of a Hr-like domain in a P-type ATPase is unprecedented and suggests new regulatory mechanisms as well as an expanded function for Hr proteins in biology. PMID:20672819

  12. An X-ray Comparison of Centrifugal Magnetospheres in Five B-type Stars

    NASA Astrophysics Data System (ADS)

    Fletcher, Corinne; Petit, Veronique; Naze, Y.; Ud-Doula, Asif; Wade, Gregg; Shultz, Matt; Held Cohen, David

    2016-01-01

    Massive stars lose a large amount of their main sequence mass through their strong stellar winds. However, the stellar wind properties and distribution are affected by the strong (~kG) dipolar magnetic fields being detected in a growing population of massive stars by the MiMeS project. In these magnetic stars the stellar wind is channeled along the closed magnetic field loops toward the magnetic equator. The wind flows from opposite hemispheres collide producing X-rays via radiative cooling. Rapidly rotating massive stars have an added centrifugal support allowing for the build up of additional material and the production of energetic X-rays. However, surveys indicate that some stars deviate from these predictions. To better understand this phenomenon, XMM Newton-EPIC and Chandra-ACIS observations were used to characterize various rapidly rotating magnetic B-type stars. The X-ray fluxes provide a comparison to the slow rotating magnetic stars, which will provide strong constraints the underlying physics of magnetospheres in massive stars.

  13. WW Geminorum: An early B-type eclipsing binary evolving into the contact phase

    SciTech Connect

    Yang, Y.-G.; Dai, H.-F.; Yin, X.-G.; Yang, Y. E-mail: yangyg@chnu.edu.cn

    2014-11-01

    WW Gem is a B-type eclipsing binary with a period of 1.2378 days. The CCD photometry of this binary was performed in 2013 December using the 85 cm telescope at the Xinglong Stations of the National Astronomical Observatories of China. Using the updated W-D program, the photometric model was deduced from the VRI light curves. The results imply that WW Gem is a near-contact eclipsing binary whose primary component almost fills its Roche lobe. The photometric mass ratio is q {sub ph} = 0.48(± 0.05). All collected times of minimum light, including two new ones, were used for the period studies. The orbital period changes of WW Gem could be described by an upward parabola, possibly overlaid by a light-time orbit with a period of P {sub mod} = 7.41(± 0.04) yr and a semi-amplitude of A = 0.0079 days(± 0.0005 days), respectively. This kind of cyclic oscillation may be attributed to the light-travel time effect via the third body. The long-term period increases at a rate of dP/dt = +3.47(±0.04) × 10{sup –8} day yr{sup –1}, which may be explained by the conserved mass transfer from the less massive component to the more massive one. With mass transfer, the massive binary WW Gem may be evolving into a contact binary.

  14. [Prognostic value of changes in concentration of brain natriuretic peptide, TNF-alpha factor and Interleukin-6 in chronic cardiac failure].

    PubMed

    Volkova, S Iu

    2008-01-01

    During 6 months therapy initial and final N-terminal pro-B-type natriuretic peptide. TNF-alpha, and IL-6 level in blood plasma were determined in 61 ischemic CHI cases with left ventricular ejection fraction below 40%. The patients were followed up for next 24.7 +/- 11.5 months. In period of 6 months following up associated with performed therapy 67.9% of patients showed a positive clinical effect, combined with a decrease of plasma pools of neurohumoral mediators (NM) in 51.4%-71.4% of cases (in dependence on studied NM). There were selected the 4 variants of combinations of clinical efficacy and NM dynamics which failed to coincide in a half of observations for NT-pro BNP and IL-6, and in a third for TNF-alpha. Multivariate analysis of conformities showed, that a decrease of all NM during therapy significantly relates with patient surviving. In a group with a decrease of plasma NT-pro BNP level associated with therapy during consequent following up no lethal outcome was recorded, compared to 16% in a group with a rise in NT-pro BNP (a = 0.2). Lethal outcome was fixed in 4.2% in a group with a decrease in TNF-alpha, compared to 33.3% in a group with elevation in TNF-alpha (a = 0.016); and in 5% in a group with a fall in IL-6, compared to 23.1% in a group with an elevation of IL-6 (a = 0.04).

  15. Optimizing fluid management in patients with acute decompensated heart failure (ADHF): the emerging role of combined measurement of body hydration status and brain natriuretic peptide (BNP) levels.

    PubMed

    Valle, Roberto; Aspromonte, Nadia; Milani, Loredano; Peacock, Frank W; Maisel, Alan S; Santini, Massimo; Ronco, Claudio

    2011-11-01

    The study tests the hypothesis that in patients admitted with acutely decompensated heart failure (ADHF), achievement of adequate body hydration status with intensive medical therapy, modulated by combined bioelectrical vectorial impedance analysis (BIVA) and B-type natriuretic peptide (BNP) measurement, may contribute to optimize the timing of patient's discharge and to improve clinical outcomes. Three hundred patients admitted for ADHF underwent serial BIVA and BNP measurement. Therapy was titrated to reach a BNP value of <250 pg/ml, whenever possible. Patients were categorized as early responders (rapid BNP fall below 250 pg/ml); late responders (slow BNP fall below 250 pg/ml, after aggressive therapy); and non-responders (BNP persistently >250 pg/ml). Worsening of renal function (WRF) was evaluated during hospitalization. Death and rehospitalization were monitored with a 6-month follow-up. BNP value on discharge of ≤250 pg/ml led to a 25% event rate within 6 months (Group A: 17.4%; Group B: 21%, Chi2; n.s.), whereas a value >250 pg/ml (Group C) was associated with a far higher percentage (37%). At discharge, body hydration was 73.8 ± 3.2% in the total population and 73.2 ± 2.1, 73.5 ± 2.8, 74.1 ± 3.6% in the three groups, respectively. WRF was observed in 22.3% of the total. WRF occurred in 22% in Group A, 32% in Group B, and 20% in Group C (P = n.s.). Our study confirms the hypothesis that combined BNP/BIVA sequential measurements help to achieve adequate fluid balance status in patients with ADHF and can be used to drive a "tailored therapy," allowing clinicians to identify high-risk patients and possibly to reduce the incidence of complications secondary to fluid management strategies.

  16. Plasma arginine vasopressin, atrial natriuretic peptide and brain natriuretic peptide responses to long-term field training in the heat: effects of fluid ingestion and acclimatization.

    PubMed

    Mudambo, K S; Coutie, W; Rennie, M J

    1997-01-01

    The maintenance of blood volume during exercise, especially in a hot environment, is of major importance for continued performance. In order to investigate the relationships between exercise, type and amount of fluid intake and the degree of acclimatization to heat stress and on responses of arginine vasopressin (AVP), atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), we studied 24 soldiers during and after jogging/walking exercise both before and after acclimatization to field training at [mean (SE)] 40 (0.7) degrees C and 32 (3)% relative humidity. The running exercise was carried out under three conditions, i.e., (1) without any fluid intake, (2) with intake of water or (3) with intake of a dextrose/electrolyte solution. Venous blood samples were drawn before exercise, at the end of exercise and at 15 min and 60 min afterwards. Acclimatization resulted in significant losses of body mass, total body water, plasma volume, ANP and increases in plasma osmolality, packed cell volume and AVP at rest but without any significant changes in BNP. During exercise with no fluid intake, there was a significant rise in plasma osmolality, Na+ and AVP, but no significant alterations in plasma ANP and BNP were observed. When subjects ingested water or dextrose/electrolyte solution during exercise, ANP rose by 234% and 431% respectively and BNP rose by 398% and 583% respectively without any significant increase in AVP. The results suggest that, during acclimatization, the subjects became slightly dehydrated. Alterations in response to changes in body water status appear to be greater for AVP than ANP or BNP at rest. During exercise in the heat ANP and BNP may play complementary roles. PMID:9088840

  17. Responses of cardiac natriuretic peptides after paroxysmal supraventricular tachycardia: ANP surges faster than BNP and CNP.

    PubMed

    Kuo, Jen-Yuan; Wang, An-Mei; Chang, Sheng-Hsiung; Hung, Chung-Lieh; Chen, Chun-Yen; Shih, Bing-Fu; Yeh, Hung-I

    2016-03-15

    Atrial natriuretic peptide (ANP) secretion increases after 30 min of paroxysmal supraventricular tachycardia (PSVT). Whether this phenomenon also applies to brain or C-type natriuretic peptides (BNP or CNP) remains unknown. Blood samples of 18 patients (41 ± 11 yr old; 4 men) with symptomatic PSVT and normal left ventricular systolic function (ejection fraction 65 ± 6%) were collected from the coronary sinus (CS) and the femoral artery (FA) before and 30 min after the induction, and 30 min after the termination of PSVT. The results showed that the ANP levels rose steeply after the PSVT and then reduced at 30 min after the termination (baseline vs. post-PSVT vs. posttermination: CS: 34.0 ± 29.6 vs. 74.1 ± 42.3 vs. 46.1 ± 32.9; FA: 5.9 ± 3.24 vs. 28.2 ± 20.7 vs. 10.0 ± 4.6 pg/ml; all P < 0.05). In contrast, compared with ANP, the increases of BNP and CNP in CS after the PSVT were less sharp, but continued to rise after the termination of tachycardia (BNP, 10.2 ± 6.4 vs. 11.3 ± 7.1 vs. 11.8 ± 7.9; CNP, 4.5 ± 1.2 vs. 4.9 ± 1.4 vs. 5.0 ± 1.4 pg/ml; all P < 0.05). The rise of BNP and CNP in FA was similarly less sharp after the PSVT and remained stationary after the termination. PSVT exerted differential effects on cardiac natriuretic peptide levels. ANP increased greater after a 30-min induced PSVT, but dropped faster after termination of PSVT, compared with BNP and CNP.

  18. Atrial Natriuretic Peptide and Type 2 Diabetes Development – Biomarker and Genotype Association Study

    PubMed Central

    Jujić, Amra; Nilsson, Peter M.; Engström, Gunnar; Hedblad, Bo; Melander, Olle; Magnusson, Martin

    2014-01-01

    Background We have recently shown that low plasma levels of mid-regional atrial natriuretic peptide (MR-ANP) predict development of diabetes and glucose progression over time, independently of known risk factors for diabetes development. However, since MR-ANP levels might be influenced by unknown factors causing diabetes, we cannot rule out that such relationship might be confounded. Previous studies have shown an association of a single nucleotide polymorphism rs5068 on the natriuretic peptide precursor A (NPPA) locus gene with higher levels of circulating ANP. Since gene variants are inherited randomly and not subject to confounding, we aimed to investigate whether the variant rs5068 within the NPPA locus is associated with incident type 2 diabetes. Methods We genotyped the variant rs5068 within the NPPA locus in 27,307 individuals without known diabetes from the Malmö Diet Cancer Study. Incident diabetes was retrieved through national and regional registers (median follow-up time of 14 years, 2,823 incident diabetes cases). Results In Cox regression analysis adjusted for age, sex and BMI, we found that the carriers of at least one copy of the G allele of rs5068 had lower likelihood of incident diabetes within 14 years (HR = 0.88, 95% CI 0.78–0.99, p = 0.037). Conclusion Our results indicate a role of the ANP system in the etiology of type 2 diabetes and might help provide insight in the metabolic actions of natriuretic peptides and the pathophysiology of type 2 diabetes. PMID:24586593

  19. A novel lipid natriuretic factor in the renal medulla: sphingosine-1-phosphate.

    PubMed

    Zhu, Qing; Xia, Min; Wang, Zhengchao; Li, Pin-Lan; Li, Ningjun

    2011-07-01

    Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite formed by phosphorylation of sphingosine. S1P has been indicated to play a significant role in the cardiovascular system. It has been shown that the enzymes for S1P metabolism are expressed in the kidneys. The present study characterized the expression of S1P receptors in the kidneys and determined the role of S1P in the control of renal hemodynamics and sodium excretion. Real-time RT-PCR analyses showed that S1P receptors S1P1, S1P2, and S1P3 were most abundantly expressed in the renal medulla. Immunohistochemistry revealed that all three types of S1P receptors were mainly located in collecting ducts. Intramedullary infusion of FTY720, an S1P agonist, produced a dramatic increase in sodium excretion by twofold and a small but significant increase in medullary blood flow (16%). Administration of W146, an S1P1 antagonist, into the renal medulla blocked the effect of FTY720 and decreased the sodium excretion by 37% when infused alone. The antagonists of S1P2 and S1P3 had no effect. FTY720 produced additive natriuretic effects in combination with different sodium transporter inhibitors except amiloride, an epithelial sodium channel blocker. In the presence of nitric oxide synthase inhibitor l-NAME, FTY720 still increased sodium excretion. These data suggest that S1P produces natriuretic effects via activation of S1P1 in the renal medulla and this natriuretic effect may be through inhibition of epithelial sodium channel, which is nitric oxide independent. It is concluded that S1P is a novel diuretic factor in the renal medulla and may be an important regulator of sodium homeostasis.

  20. Human scavenger receptor class B type II (SR-BII) and cellular cholesterol efflux.

    PubMed Central

    Mulcahy, Jane V; Riddell, Dave R; Owen, James S

    2004-01-01

    Although studies in recombinant cells indicate that scavenger receptor class B, type I (SR-BI) can promote cholesterol efflux, investigations in transgenic mice overexpressing or deficient in SR-BI endorse its physiological function as selectively sequestering cholesteryl esters from high-density lipoproteins (HDLs). Less clear is the role of SR-BII, a splice variant of the SR-B gene that differs only in the C-terminal cytoplasmic domain. Here, we identify several putative signalling motifs in the C-terminus of human SR-BII, which are absent from SR-BI, and hypothesize that these motifs interact with signalling molecules to mobilize stored cholesteryl esters and/or promote the efflux of intracellular free cholesterol. 'Pull-down' assays using a panel of tagged SH3 (Src homology 3) domains showed that cytoplasmic SR-BII, but not cytoplasmic SR-BI, bound the SH3 domain of phospholipase C-gamma1; this interaction was not, however, detected under more physiological conditions. Specific anti-peptide antisera identified SR-BII in human monocyte/macrophage THP-1 cells and, in recombinant cells, revealed receptor localization to caveolae, a plasma membrane microdomain that concentrates signal-transducer molecules and acts as a conduit for cholesterol flux between cells and lipoproteins. Consistent with its caveolar localization, expression of human SR-BII in recombinant Chinese hamster ovary cells (CHO-SR-BII) was associated with increased HDL-mediated cholesterol efflux. Nevertheless, when CHO-SR-BII cells were pre-loaded with cholesteryl [(3)H]oleate and incubated with HDL, cholesteryl ester stores were not reduced compared with control cells. We conclude that although human SR-BII is expressed by macrophages, contains cytoplasmic signalling motifs and localizes to caveolae, its ability to stimulate cholesterol efflux does not reflect enhanced hydrolysis of stored cholesteryl esters. PMID:14570588

  1. High-Density Lipoproteins Rescue Diabetes-Impaired Angiogenesis via Scavenger Receptor Class B Type I.

    PubMed

    Tan, Joanne T M; Prosser, Hamish C G; Dunn, Louise L; Vanags, Laura Z; Ridiandries, Anisyah; Tsatralis, Tania; Leece, Laura; Clayton, Zoë E; Yuen, Sui Ching G; Robertson, Stacy; Lam, Yuen Ting; Celermajer, David S; Ng, Martin K C; Bursill, Christina A

    2016-10-01

    Disordered neovascularization and impaired wound healing are important contributors to diabetic vascular complications. We recently showed that high-density lipoproteins (HDLs) enhance ischemia-mediated neovascularization, and mounting evidence suggests HDL have antidiabetic properties. We therefore hypothesized that HDL rescue diabetes-impaired neovascularization. Streptozotocin-induced diabetic mice had reduced blood flow recovery and neovessel formation in a hindlimb ischemia model compared with nondiabetic mice. Reconstituted HDL (rHDL) infusions in diabetic mice restored blood flow recovery and capillary density to nondiabetic levels. Topical rHDL application rescued diabetes-impaired wound closure, wound angiogenesis, and capillary density. In vitro, rHDL increased key mediators involved in hypoxia-inducible factor-1α (HIF-1α) stabilization, including the phosphoinositide 3-kinase/Akt pathway, Siah1, and Siah2, and suppressed the prolyl hydroxylases (PHD) 2 and PHD3. rHDL rescued high glucose-induced impairment of tubulogenesis and vascular endothelial growth factor (VEGF) A protein production, a finding associated with enhanced phosphorylation of proangiogenic mediators VEGF receptor 2 and endothelial nitric oxide synthase. Siah1/2 small interfering RNA knockdown confirmed the importance of HIF-1α stability in mediating rHDL action. Lentiviral short hairpin RNA knockdown of scavenger receptor class B type I (SR-BI) in vitro and SR-BI(-/-) diabetic mice in vivo attenuated rHDL rescue of diabetes-impaired angiogenesis, indicating a key role for SR-BI. These findings provide a greater understanding of the vascular biological effects of HDL, with potential therapeutic implications for diabetic vascular complications. PMID:27284113

  2. [C-TYPE NATRIURETIC PEP- TIDE: WHAT, WHERE AND WHAT FOR IS THIS?].

    PubMed

    Korostyshevskaya, I M; Maksimov, V F; Rudenko, N S

    2015-05-01

    The up-to-day world-wide data about the structure, distribution, and physiological effects of the most poorly known among the natriuretic peptides--the C-type (CNP)--are summarized in the review. Despite its name, this peptide does not stimulate sodium excretion but shares the prominent vasodilating and antyproliferating effects in different organs and tissues. The special emphasis is attended to CNP functions in central nervous system. The information about the peptide molecular biology, including intracellular processing, blood peptide concentration, specific receptors structure, and signaling pathways in target cells is presented.

  3. Left ventricular dysfunction, natriuretic peptides, and mortality in an urban population

    PubMed Central

    McDonagh, T; Cunningham, A; Morrison, C; McMurray, J; Ford, I; Morton, J; Dargie, H

    2001-01-01

    OBJECTIVE—To report the mortality of left ventricular systolic dysfunction (LVD), assessed objectively by echocardiography, and its association with natriuretic peptide hormones in a random sample of 1640 men and women aged 25-74 years from a geographical, urban population.
METHODS—Left ventricular function was measured by echocardiography in 1640 attendees studied in 1992-3. LVD was defined as a left ventricular ejection fraction (LVEF) ⩽ 30%. Plasma concentrations of N-terminal atrial natriuretic peptide (N-ANP) and brain natriuretic peptide (BNP) were measured by standard radioimmunoassays. Mortality was documented at four years.
RESULTS—The four year all cause mortality rate in the whole cohort was 4.9% (80 deaths). It was 21% (nine deaths) in those with an LVEF ⩽ 30% and 4% in those whose LVEF was > 30% (p < 0.001). The median (interquartile range) BNP concentration in those who died was 16.9 pg/ml (8.8-27) and 7.8 pg/ml (3.4-13) in survivors (p < 0.0001). Similarly, N-ANP had a median concentration of 2.35 ng/ml (1.32-3.36) in those with a fatal outcome and 1.27 ng/ml (0.9-2.0) in those alive at four years (p < 0.0001). Subjects with an LVEF ⩽ 40% also had a significant mortality rate of 17% if they also had a BNP concentration ⩾ 17.9 pg/ml compared with 6.8% if their BNP was below this concentration (p = 0.013). Multivariate analysis revealed the independent predictors of four year all cause mortality to be increasing age (p < 0.001), a BNP concentration ⩾ 17.9 pg/ml (p = 0.006), the presence of ischaemic heart disease (p = 0.03), and male sex (p = 0.04).
CONCLUSIONS—LVD is associated with a considerable mortality rate in this population. BNP also independently predicts outcome. In addition to its role as a diagnostic aid in chronic heart failure and LVD, it provides prognostic information and clarifies the meaning of a given degree of LVD.


Keywords: epidemiology; left ventricular dysfunction

  4. Atrial natriuretic factor mRNA and binding sites in the adrenal gland.

    PubMed Central

    Nunez, D J; Davenport, A P; Brown, M J

    1990-01-01

    The factor inhibiting aldosterone secretion produced by the adrenal medulla may be atrial natriuretic factor (ANF), since the latter abolishes aldosterone release in response to a number of secretagogues, including angiotensin II and K+. In this study we have shown that cells in the adrenal medulla contain ANF mRNA and therefore have the potential to synthesize this peptide. The presence of binding sites for ANF predominantly in the adrenal zona glomerulosa suggests that, if ANF is synthesized in the medulla and transferred to the cortex, it may affect mineralocorticoid status. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. PMID:2146954

  5. Localization of atrial natriuretic peptide receptors in the rat tongue and hard palate.

    PubMed

    Park, B K; Cho, E S; Lee, J D; Oh, C; Lee, M S; Kim, S Z; Kim, S H; Cho, K W

    1998-08-01

    Atrial natriuretic peptide (ANP) receptors were characterized in rat oral mucosa using quantitative in vitro autoradiography and activation of particulate guanylyl cyclase (GC) by natriuretic peptides. Competition-binding analysis performed by quantitative in vitro autoradiography demonstrated specific [125I]rANP(1-28) binding sites in the tongue and hard palate. The precise location of this binding was revealed on the basal and parabasal cells of the epithelia by microautoradiography. The dissociation constant (Kd) and maximal binding capacity (Bmax) of these sites were 3.34+/-1.35 nM and 2.71+/-2.21 fmol/mm2 on the epithelium of the tongue, and 4.09+/-1.52 nM and 3.45+/-3.01 fmol/mm2 on the epithelium of the hard palate, respectively. Receptor subtypes were characterized by competition with des [Gln18, Ser19, Gly20, Leu21, Gly22] ANP(4-23) (C-ANP), a specific ligand for the clearance receptor (NPR-C). These binding sites were displaced by C-ANP with inhibition constant (Ki) of 8.96+/-3.18 nM and Bmax of 2.89+/-2.45 fmol/mm2 on the epithelium of the tongue, and Ki of 9.12+/-2.71 nM and Bmax of 3.08+/-2.94 fmol/mm2 on the epithelium of the hard palate, respectively. Production of cyclic GMP by particulate GC in the epithelial membranes of the tongue and hard palate was stimulated by rANP(1-28), porcine brain natriuretic peptide (BNP)(1-26), and C-type natriuretic peptide (CNP)(1-22) in a dose-dependent manner. These results indicate that ANP-binding sites in the epithelium of the tongue and hard palate are mainly clearance receptors (NPR-C) but biological receptors (NPR-A and/or NPR-B) with GC activity are also present, and suggest that ANP may have a role in the proliferation of the oral epithelial cells, especially in the tongue and hard palate.

  6. Characterization of atrial natriuretic peptide receptors in brain microvessel endothelial cells

    NASA Technical Reports Server (NTRS)

    Whitson, Peggy A.; Huls, M. H.; Sams, Clarence F.

    1989-01-01

    In view of the suggestions by Chabrier et al. (1987) and Steardo and Nathanson (1987) that atrial natriuretic peptide (ANP) may play a role in the fluid homeostasis of the brain, the ANP receptors in primary cultures of bovine brain microvessel endothelian cells were quantitated and characterized. Results of partition binding studies and the effect of cGMP additions indicated the presence of at least two types of ANP receptors, with the majority of the receptors being the nonguanylate cyclase coupled receptors. The presence of at least two ANP receptor types suggests an active role for ANP in regulating brain endothelial cell function.

  7. [Hormones and osteoporosis update. Effects of natriuretic peptides on endochondral bone growth].

    PubMed

    Yasoda, Akihiro; Nakao, Kazuwa

    2009-07-01

    We revealed that the C-type natriuretic peptide (CNP) and its receptor guanylyl cyclase-B (GC-B) system is a potent and physiological stimulator of endochondral bone growth by using transgenic and knockout mice. In humans, one form of skeletal dysplasias, acromesomelic dysplasia, type Maroteaux, was reported to be caused by loss of function mutations in the GC-B gene. Further studies are needed for clarifying the patho-physiological roles of the CNP/GC-B system on human skeletal dysplasias. Moreover, we will have to translate this effect of the CNP/GC-B system on endochondral bone growth into skeletal dysplasias.

  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. The response of circulating brain natriuretic peptide to academic stress in college students.

    PubMed

    Amir, Offer; Sagiv, Moran; Eynon, Nir; Yamin, Chen; Rogowski, Ori; Gerzy, Yishay; Amir, Ruthie E

    2010-01-01

    Brain natriuretic peptide (BNP), a cardiac peptide, has been implicated in the regulation of hypothalamic-pituitary-adrenocortical (HPA) responses to psychological stressors. The influence of academic stress on circulating concentration of the N-terminal fragment of BNP precursor (NT-proBNP), and in relation to the stress hormone (cortisol) response was studied in 170 college students undergoing major examinations. Just prior to the examination, we measured self-estimated stress level, systolic, and diastolic blood pressure (SBP, DBP), heart rate (HR), plasma levels of cortisol, and NT-proBNP. These parameters were compared to the participants' baseline measurements, taken at the same hour of a different 'control day', without a major examination to induce stress. Hemodynamic variables (SBP, DBP, and HR) increased on the examination day compared with baseline values ( p < 0.001). Circulating cortisol concentration increased before examinations (+42%, p < 0.001). The response to stress was marked by a significant decrease in plasma NT-proBNP concentration (-40%, p < 0.001). We found in males a significant interaction between the cortisol elevation with examination stress and the NT-proBNP reduction ( p = 0.02). In response to academic stress, the plasma cortisol elevation was accompanied by a marked reduction in plasma NT-proBNP level. These data may indicate that mental stress entails an interface between the HPA axis and the peripheral natriuretic peptide system, leading to reciprocating changes in circulating levels of the corresponding hormones.

  10. Natriuretic peptides induce weak VASP phosphorylation at Serine 239 in platelets.

    PubMed

    Borgognone, Alessandra; Lowe, Kate L; Watson, Stephen P; Madhani, Melanie

    2014-01-01

    Cyclic guanosine-3',5'-monophoshate (cGMP) is the common second messenger for the cardiovascular effects of nitric oxide (NO) and natriuretic peptides (NP; e.g. atrial NP [ANP]), which activate soluble and particulate guanylyl cyclases, respectively. The role of NO in regulating cGMP and platelet function is well documented, whereas there is little evidence supporting a role for NPs in regulating platelet reactivity. By studying platelet aggregation and secretion in response to a PAR-1 peptide, collagen and ADP, and phosphorylation of the cGMP-dependent protein kinase (PKG) substrate vasodilator-stimulated phosphoprotein (VASP) at serine 239, we evaluated the effects of NPs in the absence or presence of the non-selective cGMP and cAMP phosphodiesterase (PDE) inhibitor, 3-isobutyl-1-methylxanthine (IBMX). Our results show that NPs, possibly through the clearance receptor (natriuretic peptide receptor-C) expressed on platelet membranes, increase VASP phosphorylation but only following PDE inhibition, indicating a small, localised cGMP synthesis. As platelet aggregation and secretion measured under the same conditions were not affected, we conclude that the magnitude of PKG activation achieved by NPs in platelets per se is not sufficient to exert functional inhibition of platelet involvement in haemostasis. PMID:23469931

  11. Interactions between the sympathetic nervous system and atrial natriuretic factor in the control of renal functions.

    PubMed

    Genovesi, S; Protasoni, G; Assi, C; Golin, R; Stella, A; Zanchetti, A

    1990-08-01

    We studied neural influences on the renal actions of atrial peptides in anaesthetized cats by comparing the response to atrial natriuretic factor (ANF) infusion in the innervated kidney and in the contralateral surgically denervated kidney. During ANF infusion arterial pressure decreased, the heart rate did not change and blood flow to both kidneys increased slightly. Vascular conductances became slightly but significantly higher in the denervated kidneys than in the controls. In both kidneys, the glomerular filtration rate increased transiently and significantly. Inhibition of renin release was more prompt and larger in the innervated than in the denervated kidneys. ANF infusion caused a significant increase in sodium and water excretion from both the innervated and denervated kidneys. However, the diuretic and natriuretic effect in the innervated kidneys, although proportionally greater than that in the denervated kidneys, was of shorter duration and subsided after 20 min of ANF infusion. Efferent renal nerve activity did not change during the initial 10 min of ANF infusion but thereafter increased progressively and significantly. We conclude that the effects of atrial peptides on renin release and excretory functions are influenced by renal nerve activity.

  12. Evidence that the Brain Participates in the Humoral Natriuretic Mechanism of Blood Volume Expansion in the Dog

    PubMed Central

    Kaloyanides, George J.; Balabanian, Murgurdich B.; Bowman, Ralph L.; Pool, Philip

    1978-01-01

    We examined the role of the central nervous system in the activation of the humoral natriuretic mechanism elicited by blood volume expansion. Studies were performed in anesthetized dogs pretreated with deoxycorticosterone acetate (15 mg/day) and sodium chloride for 12 days. An isolated dog kidney perfused with blood from the femoral artery of the volume expanded dog served as the bioassay system for the humoral natriuretic factor. In group I volume expansion of intact dogs (n = 14) with equilibrated blood promoted an increase in fractional sodium excretion (FENa) from a control level of 2.6±0.5 to 13.6±1.6%, P <0.001. In the isolated kidney FENa increased from 3.6±0.8 to 6.8±1.1%, P <0.01. The natriuresis from the isolated kidney occurred in the absence of significant changes in renal arterial pressure, glomerular filtration rate, plasma protein concentration, or packed cell volume, whereas renal blood flow decreased slightly. In group II (n = 20) the dogs were decapitated by means of a specially designed neck vise. In 10 dogs blood pressure was supported by a constant infusion of dopamine (3.8±0.7 μg/min per kg body weight). Despite the fact that in response to the same volume stimulus, decapitated dogs manifested an increase in blood volume and cardiac output similar in magnitude to that of intact dogs whereas the rise in mean arterial pressure of decapitated dogs exceeded that of intact dogs, the natriuretic response of decapitated dogs was significantly less than that of intact dogs. FENa in decapitated dogs increased 4.7±1.1 compared to 11.1±1.4% in intact dogs (p <0.01). Furthermore, volume expansion of decapitated dogs failed to elicit a natriuretic response from the isolated kidney. FENa in the isolated kidney measured 2.6±0.4 before and 2.6±0.4% after blood volume expansion. These data indicate that decapitation inhibits activation of the humoral natriuretic mechanism elicited by blood volume expansion and are consistent with the interpretation

  13. Discovery of a magnetic field in the early B-type star σ Lupi

    NASA Astrophysics Data System (ADS)

    Henrichs, H. F.; Kolenberg, K.; Plaggenborg, B.; Marsden, S. C.; Waite, I. A.; Landstreet, J. D.; Wade, G. A.; Grunhut, J. H.; Oksala, M. E.

    2012-09-01

    Context. Magnetic early B-type stars are rare. Indirect indicators are needed to identify them before investing in time-intensive spectropolarimetric observations. Aims: We use the strongest indirect indicator of a magnetic field in B stars, which is periodic variability of ultraviolet (UV) stellar wind lines occurring symmetric about the approximate rest wavelength. Our aim is to identify probable magnetic candidates which would become targets for follow-up spectropolarimetry to search for a magnetic field. Methods: From the UV wind line variability the B1/B2V star σ Lupi emerged as a new magnetic candidate star. AAT spectropolarimetric measurements with SEMPOL were obtained. The longitudinal component of the magnetic field integrated over the visible surface of the star was determined with the least-squares deconvolution method. Results: The UV line variations of σ Lupi are similar to what is known in magnetic B stars, but no periodicity could be determined. We detected a varying longitudinal magnetic field with amplitude of about 100 G with error bars of typically 20 G, which supports an oblique magnetic-rotator configuration. The equivalent width variations of the UV lines, the magnetic and the optical-line variations are consistent with the photometric period of 3.02 d, which we identify with the rotation period of the star. Additional observations with ESPaDOnS attached to the CFHT confirmed this discovery, and allowed the determination of a precise magnetic period. Analysis revealed that σ Lupi is a helium-strong star, with an enhanced nitrogen abundance and an underabundance of carbon, and has a chemically spotted surface. Conclusions.σ Lupi is a magnetic oblique rotator, and is a He-strong star. Like in other magnetic B stars the UV wind emission appears to originate close to the magnetic equatorial plane, with maximum emission occurring when a magnetic pole points towards the Earth. The 3.01972 ± 0.00043 d magnetic rotation period is consistent with

  14. Atrial natriuretic peptide attenuates agonist-induced pulmonary edema in mice with targeted disruption of the gene for natriuretic peptide receptor-A

    PubMed Central

    Tsai, Shu-Whei; Green, Sabrina; Grinnell, Katie L.; Machan, Jason T.; Harrington, Elizabeth O.

    2013-01-01

    Atrial natriuretic peptide (ANP) inhibits agonist-induced pulmonary edema formation, but the signaling pathway responsible is not well defined. To investigate the role of the particulate guanylate cyclase-linked receptor, natriuretic peptide receptor-A (NPR-A), we measured acute lung injury responses in intact mice and pulmonary microvascular endothelial cells (PMVEC) with normal and disrupted expression of NPR-A. NPR-A wild-type (NPR-A+/+), heterozygous (NPR-A+/−), and knockout (NPR-A−/−) mice were anesthetized and treated with thrombin receptor agonist peptide (TRAP) or lipopolysaccharide (LPS). Lung injury was assessed by lung wet-to-dry (W/D) weight and by protein and cell concentration of bronchoalveolar lavage (BAL) fluid. No difference in pulmonary edema formation was seen between NPR-A genotypes under baseline conditions. TRAP and LPS increased lung W/D weight and BAL fluid cell counts more in NPR-A−/− mice than in NPR-A+/− or NPR-A+/+ mice, but no genotype-related differences were seen in TRAP-induced increases in bloodless lung W/D weight or LPS-induced increases in BAL protein concentration. Pretreatment with ANP infusion completely blocked TRAP-induced increases in lung W/D weight and blunted LPS-induced increases in BAL cell counts and protein concentration in both NPR-A−/− and NPR-A+/+ mice. Thrombin decreased transmembrane electrical resistance in monolayers of PMVECs in vitro, and this effect was attenuated by ANP in PMVECs isolated from both genotypes. Administration of the NPR-C-specific ligand, cANF, also blocked TRAP-induced increases in lung W/D weight and LPS-induced increases in BAL cell count and protein concentration in NPR-A+/+ and NPR-A−/− mice. We conclude that ANP is capable of attenuating agonist-induced lung edema in the absence of NPR-A. The protective effect of ANP on agonist-induced lung injury and pulmonary barrier function may be mediated by NPR-C. PMID:23195629

  15. Natriuretic Peptide-Induced Catecholamine Release from Cardiac Sympathetic Neurons: Inhibition by Histamine H3 and H4 Receptor Activation

    PubMed Central

    Chan, Noel Yan-Ki; Robador, Pablo A.

    2012-01-01

    We reported previously that natriuretic peptides, including brain natriuretic peptide (BNP), promote norepinephrine release from cardiac sympathetic nerves and dopamine release from differentiated pheochromocytoma PC12 cells. These proexocytotic effects are mediated by an increase in intracellular calcium secondary to cAMP/protein kinase A (PKA) activation caused by a protein kinase G (PKG)-mediated inhibition of phosphodiesterase type 3 (PDE3). The purpose of the present study was to search for novel means to prevent the proadrenergic effects of natriuretic peptides. For this, we focused our attention on neuronal inhibitory Gαi/o-coupled histamine H3 and H4 receptors. Our findings show that activation of neuronal H3 and H4 receptors inhibits the release of catecholamines elicited by BNP in cardiac synaptosomes and differentiated PC12 cells. This effect results from a decrease in intracellular Ca2+ due to reduced intracellular cAMP/PKA activity, caused by H3 and H4 receptor-mediated PKG inhibition and consequent PDE3-induced increase in cAMP metabolism. Indeed, selective H3 and H4 receptor agonists each synergized with a PKG inhibitor and a PDE3 activator in attenuating BNP-induced norepinephrine release from cardiac sympathetic nerve endings. This indicates that PKG inhibition and PDE3 stimulation are pivotal for the H3 and H4 receptor-mediated attenuation of BNP-induced catecholamine release. Cardiac sympathetic overstimulation is characteristic of advanced heart failure, which was recently found not to be improved by the administration of recombinant BNP (nesiritide), despite the predicated beneficial effects of natriuretic peptides. Because excessive catecholamine release is likely to offset the desirable effects of natriuretic peptides, our findings suggest novel means to alleviate their adverse effects and improve their therapeutic potential. PMID:22923736

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

    PubMed

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

    2014-07-18

    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

  17. Recognition of subsets of the mammalian A/B-type core heterogeneous nuclear ribonucleoprotein polypeptides by novel autoantibodies.

    PubMed Central

    Dangli, A; Plomaritoglou, A; Boutou, E; Vassiliadou, N; Moutsopoulos, H M; Guialis, A

    1996-01-01

    The structurally related A/B-type core heterogeneous nuclear ribonucleoprotein (hnRNP) polypeptides of 34-39 kDa (A1, A2, B1 and B2) belong to a family of RNA-binding proteins that are major components of 40 S hnRNP complexes. By two-dimensional gel electrophoresis and peptide mapping analysis we compared each member of the A/B-type core proteins in the human and rat liver cells. This comparison revealed the unique presence in rat cells of major protein species, referred to as mBx polypeptides, that appeared as three charge isoforms at a position corresponding to the minor HeLa B1b protein spot. In addition, clear differences in the ratios of the A1 polypeptide to the A1b isoform were observed. The detection, in sera of patients with rheumatic autoimmune diseases, of two novel autoantibody specificities, one recognizing solely B2 protein and the second both the B2 and mBx polypeptides, helped to identify mBx proteins as new A/B-type hnRNP components, immunologically related to B2 protein. A common immunoreactive V8 protease peptide of approx. 17 kDa has been identified in B2 and mBx hnRNP polypeptides. mBx protein species are identified in cells of murine origin, and have a ubiquitous tissue distribution and developmental appearance. PMID:9003360

  18. THE O- AND B-TYPE STELLAR POPULATION IN W3: BEYOND THE HIGH-DENSITY LAYER

    SciTech Connect

    Kiminki, Megan M.; Kim, Jinyoung Serena; Bagley, Micaela B.; Rieke, George H.; Sherry, William H.

    2015-11-01

    We present the first results from our survey of the star-forming complex W3, combining VRI photometry with multiobject spectroscopy to identify and characterize the high-mass stellar population across the region. With 79 new spectral classifications, we bring the total number of spectroscopically confirmed O- and B-type stars in W3 to 105. We find that the high-mass slope of the mass function in W3 is consistent with a Salpeter IMF, and that the extinction toward the region is best characterized by an R{sub V} of approximately 3.6. B-type stars are found to be more widely dispersed across the W3 giant molecular cloud (GMC) than previously realized: they are not confined to the high-density layer (HDL) created by the expansion of the neighboring W4 H ii region into the GMC. This broader B-type population suggests that star formation in W3 began spontaneously up to 8–10 Myr ago, although at a lower level than the more recent star formation episodes in the HDL. In addition, we describe a method of optimizing sky subtraction for fiber spectra in regions of strong and spatially variable nebular emission.

  19. Change of Serum BNP Between Admission and Discharge After Acute Decompensated Heart Failure Is a Better Predictor of 6-Month All-Cause Mortality Than the Single BNP Value Determined at Admission

    PubMed Central

    De Vecchis, Renato; Ariano, Carmelina; Giandomenico, Giuseppe; Di Maio, Marco; Baldi, Cesare

    2016-01-01

    Background B-type natriuretic peptide (BNP) is regarded as a reliable predictor of outcome in patients with acute decompensated heart failure (ADHF). However, according to some scholars, a single isolated measurement of serum BNP at the time of hospital admission would not be sufficient to provide reliable prognostic information. Methods A retrospective study was carried out on patients hospitalized for ADHF, who had then undergone follow-up of at least 6 months, in order to see if there was any difference in midterm mortality among patients with rising BNP at discharge as compared to those with decreasing BNP at discharge. Medical records had to be carefully examined to divide the case records into two groups, the former characterized by an increase in BNP during hospitalization, and the latter showing a decrease in BNP from the time of admission to the time of discharge. Results Ultimately, 177 patients were enrolled in a retrospective study. Among them, 53 patients (29.94%) had increased BNPs at the time of discharge relative to admission, whereas 124 (70.06%) exhibited decreases in serum BNP during their hospital stay. The group with patients who exhibited BNP increases at the time of discharge had higher degree of congestion evident in the higher frequency of persistent jugular venous distention (odds ratio: 3.72; P = 0.0001) and persistent orthopnea at discharge (odds ratio: 2.93; P = 0.0016). Moreover, patients with increased BNP at the time of discharge had a lower reduction in inferior vena cava maximum diameter (1.58 ± 2.2 mm vs. 6.32 ± 1.82 mm; P = 0.001 (one-way ANOVA)). In contrast, there was no significant difference in weight loss when patients with increased BNP at discharge were compared to those with no such increase. A total of 14 patients (7.9%) died during the 6-month follow-up period. Cox proportional hazard analysis revealed that BNP increase at the time of discharge was an independent predictor of 6-month all-cause mortality after

  20. Change of Serum BNP Between Admission and Discharge After Acute Decompensated Heart Failure Is a Better Predictor of 6-Month All-Cause Mortality Than the Single BNP Value Determined at Admission

    PubMed Central

    De Vecchis, Renato; Ariano, Carmelina; Giandomenico, Giuseppe; Di Maio, Marco; Baldi, Cesare

    2016-01-01

    Background B-type natriuretic peptide (BNP) is regarded as a reliable predictor of outcome in patients with acute decompensated heart failure (ADHF). However, according to some scholars, a single isolated measurement of serum BNP at the time of hospital admission would not be sufficient to provide reliable prognostic information. Methods A retrospective study was carried out on patients hospitalized for ADHF, who had then undergone follow-up of at least 6 months, in order to see if there was any difference in midterm mortality among patients with rising BNP at discharge as compared to those with decreasing BNP at discharge. Medical records had to be carefully examined to divide the case records into two groups, the former characterized by an increase in BNP during hospitalization, and the latter showing a decrease in BNP from the time of admission to the time of discharge. Results Ultimately, 177 patients were enrolled in a retrospective study. Among them, 53 patients (29.94%) had increased BNPs at the time of discharge relative to admission, whereas 124 (70.06%) exhibited decreases in serum BNP during their hospital stay. The group with patients who exhibited BNP increases at the time of discharge had higher degree of congestion evident in the higher frequency of persistent jugular venous distention (odds ratio: 3.72; P = 0.0001) and persistent orthopnea at discharge (odds ratio: 2.93; P = 0.0016). Moreover, patients with increased BNP at the time of discharge had a lower reduction in inferior vena cava maximum diameter (1.58 ± 2.2 mm vs. 6.32 ± 1.82 mm; P = 0.001 (one-way ANOVA)). In contrast, there was no significant difference in weight loss when patients with increased BNP at discharge were compared to those with no such increase. A total of 14 patients (7.9%) died during the 6-month follow-up period. Cox proportional hazard analysis revealed that BNP increase at the time of discharge was an independent predictor of 6-month all-cause mortality after

  1. Effects of angiotensin, vasopressin and atrial natriuretic peptide on intraocular pressure in anesthetized rats

    NASA Technical Reports Server (NTRS)

    Palm, D. E.; Shue, S. G.; Keil, L. C.; Balaban, C. D.; Severs, W. B.

    1995-01-01

    The effects of atrial natriuretic peptide (ANP), vasopressin (AVP) and angiotensin (ANG) on blood and intraocular pressures of pentobarbital anesthetized rats were evaluated following intravenous, intracerebroventricular or anterior chamber routes of administration. Central injections did not affect intraocular pressure. Equipressor intravenous infusions of ANG raised, whereas AVP decreased, intraocular pressure. Direct infusions of a balanced salt solution (0.175 microliter/min) raised intraocular pressure between 30 and 60 min. Adding ANG or ANP slightly reduced this solvent effect but AVP was markedly inhibitory. An AVP-V1 receptor antagonist reversed the blunting of the solvent-induced rise by the peptide, indicating receptor specificity. Acetazolamide pretreatment lowered intraocular pressure, but the solvent-induced rise in intraocular pressure and inhibition by AVP still occurred without altering the temporal pattern. Thus, these effects appear unrelated to aqueous humor synthesis rate. The data support the possibility of intraocular pressure regulation by peptides acting from the blood and aqueous humor.

  2. Difference in molecular pathology of natriuretic peptides in the myocardium between acute asphyxial and cardiac deaths.

    PubMed

    Chen, Jian-Hua; Michiue, Tomomi; Ishikawa, Takaki; Maeda, Hitoshi

    2012-07-01

    In investigating death due to mechanical asphyxiation and drowning, a cardiac attack is important for discriminating between possible causes of death and as a contributory factor in death processes; however, general pathologies involving visceral congestion are often similar. The present study compared terminal cardiac dysfunction in these fatalities using the molecular pathology of atrial and brain natriuretic peptides (ANP and BNP) in the myocardium as markers of cardiac strain. Both mechanical asphyxiation (n=27) and drowning (n=23) showed significantly lower ANP and BNP mRNA expressions in bilateral ventricular walls than sudden cardiac deaths (n=36). In addition, right atrial wall BNP mRNA expression was lower in asphyxiation; however, immunostaining did not demonstrate any difference among these fatalities. Differences among the subtypes of asphyxiation or between fresh- and saltwater drowning were insignificant. These observations suggest a difference between primary heart failure in sudden cardiac death and terminal cardiac dysfunction secondary to fatal asphyxiation or drowning.

  3. Highly sensitive radioimmunoassay of atrial natriuretic peptide (ANP) in human plasma and urine

    SciTech Connect

    Marumo, F.; Sakamoto, H.; Ando, K.; Ishigami, T.; Kawakami, M.

    1986-05-29

    A highly sensitive radioimmunoassay has been established for measurement of human plasma and urine concentrations of atrial natriuretic peptide (ANP) and requires no extraction or concentration process. An antiserum was prepared from rabbits immunized with ..cap alpha..-human ANP (..cap alpha..-hANP) coupled with bovine-thyroglobulin. The sensitivity of this method was 0.2 pg/tube of synthetic ..cap alpha..-hANP utilized as authentic standard. Recovery of ..cap alpha..-hANP spiked to plasma and urine was 97.7 +/- 15.4% and 97.1 +/- 9.5% (mean +/- SD), respectively. Plasma and urinary ANP concentrations versus assay data showed satisfactory linearity. In 124 health subjects, the plasma ANP concentration was 31.7 +/- 12.0 pg/ml. Two different molecular forms of ANP in plasma and a single form in urine were found by gel permeation chromatography.

  4. Binding sites for atrial natriuretic factor (ANF) in brain: alterations in Brattleboro rats

    SciTech Connect

    McCarty, R.; Plunkett, L.M.

    1986-12-01

    Binding sites for atrial natriuretic factor (ANF-28) were analyzed in discrete brain areas of Brattleboro rats with hereditary diabetes insipidus and Long-Evans (LE) controls by quantitative autoradiography. The maximum binding capacity (Bmax) and affinity constant (Ka) for /sup 125/I-ANF-28 were elevated significantly in the subfornical organ of Brattleboro rats compared to matched LE controls. In contrast, values for Bmax and Ka for /sup 125/I-ANF-28 binding in choroid plexus and area postrema were similar for rats of the two strains. These findings are consistent with a selective upregulation of ANF-28 binding sites in the subfornical organ of Brattleboro rats which exhibit a profound disturbance in body fluid homeostasis. These alterations in ANF-28 binding sites in the subfornical organ may represent a compensatory response to the absence of vasopressin in the Brattleboro rat.

  5. Immunoreactive atrial natriuretic factor is increased in ovine model of endotoxemia

    SciTech Connect

    Lubbesmeyer, H.J.; Woodson, L.; Traber, L.D.; Flynn, J.T.; Herndon, D.N.; Traber, D.L. Thomas Jefferson Medical College, Philadelphia, PA Westfaelian Wilhelms Univ., Muenster )

    1988-04-01

    A bolus of Escherichia coli endotoxin (1.5 {mu}g/kg) was administered to chronically instrumented sheep. Immunoreactive atrial natriuretic factor (IR-ANF) was measured in extracted plasma by radioimmunoassay. There was a thirteenfold increase in IR-ANF 2 h after endotoxin administration, and IR-ANF levels remained significantly elevated during the first 6 h. A marked diuresis and natriuresis occurred between 4 and 6 h. ANF not only affects renal function but is also associated with decreased cardiac output, increased peripheral resistance (in sheep), and decreased capillary absorption (in rats). These renal and hemodynamic changes are also characteristic of the early (first 6 h) response to endotoxin. Therefore ANF should be considered as a potential mediator of renal and hemodynamic changes induced by sepsis. It is difficult to determine if ANF elevation is an epiphenomenon or a causative factor, because no antagonist of ANF is currently available.

  6. 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.

  7. C-Type Natriuretic Peptide Induces Anti-contractile Effect Dependent on Nitric Oxide, Oxidative Stress, and NPR-B Activation in Sepsis

    PubMed Central

    Pernomian, Laena; Prado, Alejandro F.; Silva, Bruno R.; Azevedo, Aline; Pinheiro, Lucas C.; Tanus-Santos, José E.; Bendhack, Lusiane M.

    2016-01-01

    Aims: To evaluate the role of nitric oxide, reactive oxygen species (ROS), and natriuretic peptide receptor-B activation in C-type natriuretic peptide-anti-contractile effect on Phenylephrine-induced contraction in aorta isolated from septic rats. Methods and Results: Cecal ligation and puncture (CLP) surgery was used to induce sepsis in male rats. Vascular reactivity was conducted in rat aorta and resistance mesenteric artery (RMA). Measurement of survival rate, mean arterial pressure (MAP), plasma nitric oxide, specific protein expression, and localization were evaluated. Septic rats had a survival rate about 37% at 4 h after the surgery, and these rats presented hypotension compared to control-operated (Sham) rats. Phenylephrine-induced contraction was decreased in sepsis. C-type natriuretic peptide (CNP) induced anti-contractile effect in aortas. Plasma nitric oxide was increased in sepsis. Nitric oxide-synthase but not natriuretic peptide receptor-B expression was increased in septic rat aortas. C-type natriuretic peptide-anti-contractile effect was dependent on nitric oxide-synthase, ROS, and natriuretic peptide receptor-B activation. Natriuretic peptide receptor-C, protein kinase-Cα mRNA, and basal nicotinamide adenine dinucleotide phosphate (NADPH)-dependent ROS production were lower in septic rats. Phenylephrine and CNP enhanced ROS production. However, stimulated ROS production was low in sepsis. Conclusion: CNP induced anti-contractile effect on Phenylephrine contraction in aortas from Sham and septic rats that was dependent on nitric oxide-synthase, ROS, and natriuretic peptide receptor-B activation. PMID:27445832

  8. The plant natriuretic peptide receptor is a guanylyl cyclase and enables cGMP-dependent signaling.

    PubMed

    Turek, Ilona; Gehring, Chris

    2016-06-01

    The functional homologues of vertebrate natriuretic peptides (NPs), the plant natriuretic peptides (PNPs), are a novel class of peptidic hormones that signal via guanosine 3',5'-cyclic monophosphate (cGMP) and systemically affect plant salt and water balance and responses to biotrophic plant pathogens. Although there is increasing understanding of the complex roles of PNPs in plant responses at the systems level, little is known about the underlying signaling mechanisms. Here we report isolation and identification of a novel Leucine-Rich Repeat (LRR) protein that directly interacts with A. thaliana PNP, AtPNP-A. In vitro binding studies revealed that the Arabidopsis AtPNP-A binds specifically to the LRR protein, termed AtPNP-R1, and the active region of AtPNP-A is sufficient for the interaction to occur. Importantly, the cytosolic part of the AtPNP-R1, much like in some vertebrate NP receptors, harbors a catalytic center diagnostic for guanylyl cyclases and the recombinant AtPNP-R1 is capable of catalyzing the conversion of guanosine triphosphate to cGMP. In addition, we show that AtPNP-A causes rapid increases of cGMP levels in wild type (WT) leaf tissue while this response is significantly reduced in the atpnp-r1 mutants. AtPNP-A also causes cGMP-dependent net water uptake into WT protoplasts, and hence volume increases, whereas responses of the protoplasts from the receptor mutant are impaired. Taken together, our results suggest that the identified LRR protein is an AtPNP-A receptor essential for the PNP-dependent regulation of ion and water homeostasis in plants and that PNP- and vertebrate NP-receptors and their signaling mechanisms share surprising similarities. PMID:26945740

  9. Asymmetrical myocardial expression of natriuretic peptides in pacing-induced heart failure.

    PubMed

    Del Ry, Silvia; Cabiati, Manuela; Lionetti, Vincenzo; Simioniuc, Anca; Caselli, Chiara; Prescimone, Tommaso; Emdin, Michele; Giannessi, Daniela

    2009-09-01

    High-frequency pacing of the left ventricle (LV) free wall causes a dyssynchronous pattern of contraction that leads to progressive heart failure (HF) with pronounced differences in regional contractility. Aim of this study was to evaluate possible changes in brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) mRNA expression in the anterior/anterior lateral region (pacing site, PS) as compared to the infero-septal region (opposite site, OS) and to explore possible association between the contractiling pattern and biomarker expression. Cardiac tissue was collected from minipigs with pacing-induced HF (n=8) and without (control, n=6). The samples were selectively harvested from the anterior left ventricular (LV) wall, PS, and from an area remote to the pacing-site, OS. BNP and CNP mRNA expression was evaluated by semi-quantitative polymerase chain reaction (PCR). A significant difference in BNP expression was found in the PS between HF animals and controls (BNP/GAPDH: 0.65+/-0.11 vs. 0.35+/-0.04, p=0.02), but not in the OS (BNP/GAPDH: 0.36+/-0.05, ns vs. controls). CNP expression was not different compared to controls, although higher levels were observed in the PS and in the OS with respect to the controls (CNP/GAPDH: controls 0.089+/-0.036, PS 0.289+/-0.23, OS 0.54+/-0.16). This finding was in tune with an increase of CNP tissue concentration (controls: 0.69+/-0.13; PS=1.56+/-0.19; OS=1.70+/-0.42 pg/mg protein; p=0.039 controls vs. OS). Higher BNP mRNA expression in the PS is consistent with a reduction in contractile function in this region, while higher CNP mRNA expression in the OS suggests the presence of concomitant endothelial dysfunction in the remote region.

  10. Temporal Change in Brain Natriuretic Peptide After Radiotherapy for Thoracic Esophageal Cancer

    SciTech Connect

    Jingu, Keiichi Nemoto, Kenji; Kaneta, Tomohiro; Oikawa, Minako; Ogawa, Yoshihiro; Ariga, Hisanori; Takeda, Ken; Sakayauchi, Toru; Fujimoto, Keisuke; Narazaki, Kakutaro; Takai, Yoshihiro; Nakata, Eiko; Fukuda, Hiroshi; Takahashi, Shoki; Yamada, Shogo

    2007-12-01

    Purpose: To investigate the relationships of plasma levels of brain natriuretic peptide (BNP) with abnormal {sup 18}F-fluorodeoxyglucose (FDG) accumulation in the myocardium corresponding to irradiated fields and temporal changes in BNP, which is used as an index of heart remodeling, after radiotherapy for the mediastinum. Materials and Methods: Brain natriuretic peptide concentrations were measured before and after radiotherapy for thoracic esophageal cancer, and the change in BNP concentration after radiotherapy was investigated. Moreover, FDG accumulation in the myocardium was investigated in patients who had undergone FDG positron emission tomography less than 14 days before or after measurement of BNP concentration, and the Mann-Whitney U test was used to detect significant difference between BNP concentrations in patients with and without abnormal FDG accumulation corresponding to the irradiated field. Results: There was significant difference between the levels of BNP in patients without abnormal FDG accumulation in the irradiated myocardium and in patients with abnormal FDG accumulation (p < 0.001). The levels of BNP in the 9-24 months after radiotherapy group and in the >24 months after radiotherapy group were significantly higher than the levels in the before radiotherapy group, immediately after radiotherapy group, 1-2 months after radiotherapy group, and control group. Conclusions: The level of BNP was significantly increased more than 9 months after the start of radiotherapy and was significantly higher in patients who had high FDG accumulation corresponding to the irradiated field. The results of this study indicate that BNP concentration might be an early indicator of radiation-induced myocardial damage.

  11. Pathophysiology of sudden cardiac death as demonstrated by molecular pathology of natriuretic peptides in the myocardium.

    PubMed

    Chen, Jian-Hua; Michiue, Tomomi; Ishikawa, Takaki; Maeda, Hitoshi

    2012-11-30

    Various heart diseases present with sudden death; however, it is difficult to interpret the severity of or difference in respective preexisting and terminal cardiac dysfunction based on conventional morphology. The present study investigated the cardiac pathophysiology employing quantitative mRNA measurement of atrial and brain natriuretic peptides (ANP and BNP) in the myocardium as markers of cardiac strain, using autopsy materials consisting of acute ischemic heart disease (AIHD, n=40) with/without the pathology of apparent myocardial necrosis (n=19/21), recurrent myocardial infarction (RMI, n=19), chronic congestive heart disease (CHD, n=11) and right ventricular cardiomyopathy (RVC, n=5), as well as hemopericardium (HP, n=11) due to myocardial infarction (n=5) and aortic rupture (n=6), and acute pulmonary thromboembolism (PTE, n=5). Cardiac death groups showed higher ANP and/or BNP mRNA expressions in the left ventricle than acute fatal bleeding (sharp instrumental injury; n=15) and/or mechanical asphyxiation (strangulation; n=10). AIHD and RMI cases had similar ANP and BNP mRNA expressions in bilateral ventricular walls, but their bilateral atrial levels were lower in RMI. RVC showed higher mRNA expressions of posterior left ventricular BNP, and right ventricular and bilateral atrial ANP and BNP. HP cases had lower BNP mRNA expression in the right ventricular wall, but PTE showed lower ANP and BNP mRNA expressions in the left ventricular wall; however, these mRNA expressions at other sites were similar to those of AIHD. CHD presented findings similar to those of AIHD, but the pericardial BNP level was significantly increased. These observations indicate characteristic molecular biological responses of myocardial natriuretic peptides in individual heart diseases and suggest the possible application of molecular pathology to demonstrate cardiac dysfunction even after death.

  12. Identification and characterization of atrial natriuretic factor receptors in the rat retina

    SciTech Connect

    Fernandez-Durango, R.; Sanchez, D.; Gutkowska, J.; Carrier, F.; Fernandez-Cruz, A.

    1989-01-01

    The characteristics of atrial natriuretic factor (ANF) receptors where studied in rat retinal particulate preparations. Specific /sup 125/I-ANF binding to retinal particulate preparations was greater than 90% of total binding and saturable at a density (B/sub max/) of 40 /plus minus/ 8 fmol/mg protein with an apparent dissociation constant (K/sub d/)/sup /minus// of 6.0 /plus minus/ 2.0 pM (n=3). Apparent equilibrium conditions were established within 30 min. The K/sub d/ value of /sup 125/I-ANF binding calculated by kinetic analysis was 4.0 pM. The B/sub max/ of 60 /plus minus/ 10 fmol/mg protein and the K/sub d/ of 5 /plus minus/ 2 pM, calculated by competition analysis, were in close agreement with the values obtained from Scatchard plots or kinetic analysis. The /sup 125/I-ANF binding to retinal particulate preparations was not inhibited by 1 ..mu..M concentration of somatostatin, vasopressin, vasoactive intestinal peptide, adrenocorticotropin, tyrotropin releasing hormone, or leu-enkephalin. The rank order of potency of the unlabeled atrial natriuretic peptides for competing with specific /sup 125/I-ANF (101-126) binding sites was rANF (92-126) > rANF (101-126) > rANF (99-126) > rANF (103-126) > Tyr-Atriopeptin I > hANF (105-126) > rANF (1-126). Similar results have been obtained in peripheral tissues and mammalian brain.

  13. Characterization of atrial natriuretic peptide degradation by cell-surface peptidase activity on endothelial cells

    NASA Technical Reports Server (NTRS)

    Frost, S. J.; Whitson, P. A.

    1993-01-01

    Atrial natriuretic peptide (ANP) is a fluid-regulating peptide hormone that promotes vasorelaxation, natriuresis, and diuresis. The mechanisms for the release of ANP and for its clearance from the circulation play important roles in modulating its biological effects. Recently, we have reported that the cell surface of an endothelial cell line, CPA47, could degrade 125I-ANP in the presence of EDTA. In this study, we have characterized this degradation of 125I-ANP. The kinetics of ANP degradation by the surface of CPA47 cells were first order, with a Km of 320 +/- 60 nM and Vmax of 35 +/- 14 pmol of ANP degraded/10 min/10(5) cells at pH 7.4. ANP is degraded by the surface of CPA47 cells over a broad pH range from 7.0-8.5. Potato carboxypeptidase inhibitor and bestatin inhibited 125I-ANP degradation, suggesting that this degradative activity on the surface of CPA47 cells has exopeptidase characteristics. The selectivity of CPA47 cell-surface degradation of ANP was demonstrated when 125I-ANP degradation was inhibited in the presence of neuropeptide Y and angiotensin I and II but not bradykinin, bombesin, endothelin-1, or substance P. The C-terminal amino acids phe26 and tyr28 were deduced to be important for ANP interaction with the cell-surface peptidase(s) based on comparison of the IC50 of various ANP analogues and other natriuretic peptides for the inhibition of ANP degradation. These data suggest that a newly characterized divalent cation-independent exopeptidase(s) that selectively recognizes ANP and some other vasoactive peptides exists on the surface of endothelial cells.

  14. Preparation and Characterization of Molecularly Imprinted Polymeric Nanoparticles for Atrial Natriuretic Peptide (ANP)

    PubMed Central

    Wang, Chunyan; Howell, Mark; Raulji, Payal; Davis, Yvonne; Mohapatra, Subhra

    2013-01-01

    Natriuretic peptide receptor A (NPRA), the receptor for the cardiac hormone atrial natriuretic peptide (ANP), is expressed abundantly on cancer cells and disruption of ANP-NPRA signaling inhibits tumor burden and metastasis. Since antagonists of NPRA signaling have not provided reproducible results, we reasoned that a synthetic neutralizing antibody to ANP, which has high selectivity and affinity for ANP, could be used to regulate ANP levels and attenuate NPRA signaling. In this study, we prepared molecularly imprinted polymer nanoparticles (MIPNPs) for ANP using a short peptide of ANP as the template and determined their binding affinity and selectivity. The MIPNPs were prepared by precipitation polymerization using NH2-SLRRSS-CONH2, which is a short peptide from ANP as template, methacrylic acid (MAA) and N-isopropylacrylamide (NIPAm) as functional monomers, bis-acrylamide (BIS) as crosslinker. The average diameter of MIPNPs and non-imprinted nanoparticles (NIPNPs) in water is 215.8 ±4.6 nm and 197.7±3.1 nm respectively. The binding isotherm analysis showed that MIPNPs have a much higher binding affinity for template peptide and ANP than NIPNPs. Scatchard analysis gave an equilibrium dissociation constant, Kd of 7.3 μM with a binding capacity 106.7 μmol/g for template peptide and Kd of 7.9 μM with a binding capacity of 36.0 μmol/g for ANP. Measurements of binding kinetics revealed that MIPNPs reach protein adsorption equilibrium in 30 min. MIPNPs found to have high specificity for ANP with little affinity for BSA or scrambled ANP peptide. MIPNPs also recognized and adsorbed ANP in cell culture media spiked with ANP and human plasma. Taken together, these results indicate that MIPNPs have high affinity and selectivity for ANP and can be used as a synthetic antibody for modulating ANP-NPRA signaling in cancers. PMID:23459692

  15. The structure of the digitalislike and natriuretic factors identified as macrocyclic derivatives of the inorganic carbon suboxide.

    PubMed

    Kerek, F

    2000-09-01

    The Natriuretic and Endogenous DigitalisLike Factors (EDLFs) are disclosed to be cyclomeric and macroring closed derivatives of the inorganic carbon suboxide. The macrocyclic cyclohexamer with six carbon suboxide units has a molar mass of 408.2 Da, as previously been found for the EDLF of animal origin. The anhydrous cyclohexameric factor is lipophilic but is transformed into more hydrophilic derivatives by the stepwise addition of water. Based on the present findings, it appears that EDLFs exist in solution as an equilibrium mixture of lipophilic and hydrophilic forms and not as a single chemical substance. This structural assumption better accounts for the earlier observed highly anomalous properties of EDLFs. The simultaneously found higher molar mass (4,100 and 4,900 Da) macrocyclic carbon suboxide derivatives are tentatively identified as the Natriuretic factors. PMID:11016817

  16. 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

  17. Physiological levels of A-, B- and C-type natriuretic peptide shed the endothelial glycocalyx and enhance vascular permeability.

    PubMed

    Jacob, Matthias; Saller, Thomas; Chappell, Daniel; Rehm, Markus; Welsch, Ulrich; Becker, Bernhard F

    2013-05-01

    Atrial natriuretic peptide (ANP) is a peptide hormone released from the cardiac atria during hypervolemia. Though named for its well-known renal effect, ANP has been demonstrated to acutely increase vascular permeability in vivo. Experimentally, this phenomenon was associated with a marked shedding of the endothelial glycocalyx, at least for supraphysiological intravascular concentrations. This study investigates the impact and mechanism of action of physiological doses of ANP and related peptides on the vascular barrier. In isolated guinea pig hearts, prepared and perfused in a modified Langendorff mode with and without the intravascular presence of the colloid hydroxyethyl starch (HES), we measured functional changes in vascular permeability and glycocalyx shedding related to intracoronary infusion of physiological concentrations of A-, B- and C-type natriuretic peptide (ANP, BNP and CNP). Significant coronary venous washout of glycocalyx constituents (syndecan-1 and heparan sulfate) was observed. As tested for ANP, this effect was positively related to the intracoronary concentration. Intravascular shedding of the glycocalyx was morphologically confirmed by electron microscopy. Also, functional vascular barrier competence decreased, as indicated by significant increases in transudate formation and HES extravasation. Ortho-phenanthroline, a non-specific inhibitor of matrix metalloproteases, was able to reduce ANP-induced glycocalyx shedding. These findings suggest participation of natriuretic peptides in pathophysiological processes like heart failure, inflammation or sepsis. Inhibition of metalloproteases might serve as a basis for future therapeutical options.

  18. A C-type natriuretic peptide from the venom of the platypus (Ornithorhynchus anatinus): structure and pharmacology.

    PubMed

    de Plater, G M; Martin, R L; Milburn, P J

    1998-07-01

    A peptide which relaxes rat uterine smooth muscle and exhibits homology with the mammalian C-type natriuretic peptide (CNP) has previously been identified in platypus (Ornithorhynchus anatinus) venom from its partial N-terminal amino acid sequence. In this study we describe the purification, detailed structure, synthesis and pharmacological characteristics of this peptide, which has been designated ovCNP-39 (Ornithorhynchus venom C-type natriuretic peptide). Elucidation of the 39-residue amino acid sequence confirms the homology with mammalian CNPs. These peptides produce hypotension in vivo and relax smooth muscle in vitro, but are poorly characterised in terms of physiological function. ovCNP-39 is equipotent with human/rat/porcine CNP-22 in eliciting cyclic guanosine 5'-monophosphate (cGMP) elevation in cultured vascular smooth muscle cells, suggesting that, like CNP, it acts through the ANPB natriuretic peptide receptor subtype. The direct elevation of cGMP in vascular smooth muscle by ovCNP-39 may underlie the vasodilatory effects of platypus envenomation. PMID:9827022

  19. Brain Natriuretic Peptide Stimulates Lipid Metabolism through Its Receptor NPR1 and the Glycerolipid Metabolism Pathway in Chicken Adipocytes.

    PubMed

    Huang, H Y; Zhao, G P; Liu, R R; Li, Q H; Zheng, M Q; Li, S F; Liang, Z; Zhao, Z H; Wen, J

    2015-11-01

    Brain natriuretic peptide (BNP) is related to lipid metabolism in mammals, but its effect and the molecular mechanisms underlying it in chickens are incompletely understood. We found that the level of natriuretic peptide precursor B (NPPB, which encodes BNP) mRNA expression in high-abdominal-fat chicken groups was significantly higher than that of low-abdominal-fat groups. Partial correlations indicated that changes in the weight of abdominal fat were positively correlated with NPPB mRNA expression level. In vitro, compared with the control group, preadipocytes with NPPB interference showed reduced levels of proliferation, differentiation, and glycerin in media. Treatments of cells with BNP led to enhanced proliferation and differentiation of cells and glycerin concentration, and mRNA expression of its receptor natriuretic peptide receptor 1 (NPR1) was upregulated significantly. In cells exposed to BNP, 482 differentially expressed genes were identified compared with controls without BNP. Four genes known to be related to lipid metabolism (diacylglycerol kinase; lipase, endothelial; 1-acylglycerol-3-phosphate O-acyltransferase 1; and 1-acylglycerol-3-phosphate O-acyltransferase 2) were enriched in the glycerolipid metabolism pathway and expressed differentially. In conclusion, BNP stimulates the proliferation, differentiation, and lipolysis of preadipocytes through upregulation of the levels of expression of its receptor NPR1 and key genes enriched in the glycerolipid metabolic pathway. PMID:26463554

  20. Two fission yeast B-type cyclins, cig2 and Cdc13, have different functions in mitosis.

    PubMed Central

    Bueno, A; Russell, P

    1993-01-01

    Cyclin B interacts with Cdc2 kinase to induce cell cycle events, particularly those of mitosis. The existence of cyclin B subtypes in several species has been known for some time, leading to speculation that key events of mitosis may be carried out by distinct functional classes of Cdc2/cyclin B. We report the discovery of cig2, a third B-type cyclin gene in Schizosaccharomyces pombe. Disruption of cig2 delays the onset of mitosis, to the degree that a cig2 null allele rescues mitotic catastrophe mutants, including those that are unable to carry out the inhibitory tyrosyl phosphorylation of Cdc2 kinase. Consistent with this, a cig2 null allele exhibits synthetic lethal interactions with cdc25ts and cdc2ts mutations. Mitotic phenotypes caused by disruption of cig2 are not reversed by increased production of Cdc13, the other fission yeast B-type cyclin that functions in mitosis. Likewise, a cdc13ts mutation is not rescued by increased gene dosage of cig2+. These data indicate that Cdc13 and Cig2 interact with Cdc2 to carry out different functions in mitosis. We suggest that some cyclin B subtypes found in other species, including humans, are also likely to have distinct, nonoverlapping functions in mitosis. Images PMID:8455610

  1. Effects of structural imperfection on gelatinization characteristics of amylopectin starches with A- and B-type crystallinity.

    PubMed

    Genkina, Natalia K; Wikman, Jeanette; Bertoft, Eric; Yuryev, Vladimir P

    2007-07-01

    The aim of the present work was to investigate the effect of physical structures on the properties of starch granules. Starches with a high amylopectin content possessing A- and B-type crystallinity were chosen for the study. The gelatinization temperature decreased in the following order: maize (A) > potato (B) > wheat (A) > barley (A), which did not reflect a correlation with the type of crystallinity. Low values of gelatinization temperature were accompanied with high free surface energy of the crystallites. It is proposed that these data are caused by different types of imperfections in starch crystals. Annealing resulted in an enhancement of the gelatinization temperature and a decrease of the free surface energy of the crystallites for all starches reflecting a partial improvement of crystalline perfection. A limited acid hydrolysis (lintnerization) of the starches decreased the gelatinization temperature because of a partial disruption of the crystalline lamellae and an increase of the amount of defects on the edges of the crystallites. Annealing of the lintnerized starches improved the structure of maize and potato starch, giving them similar structural and physicochemical parameters, which was opposite the behavior of the annealed sample from wheat. The possible nature of removable and nonremovable defects inside the crystalline region of the starch granules is discussed. It is concluded that, besides the allomorphic A- and B-types of crystal packing, physical defects in the crystals possess a major impact on starch gelatinization.

  2. Influence of doxazosin on biosynthesis of S100A6 and atrial natriuretic factor peptides in the heart of spontaneously hypertensive rats.

    PubMed

    Kasacka, Irena; Piotrowska, Żaneta; Filipek, Anna; Majewski, Mariusz

    2016-02-01

    Hypertension frequently results in severe complications in cardiovascular system and histopathological changes in the heart. To better understand the cellular processes and signaling pathways responsible for the proper functioning of the heart, we decided to check whether doxazosin affects the density of structures containing S100A6 and atrial natriuretic factor in the heart of spontaneously hypertensive rats. The aim of this study is to find differences in the density of the structures containing S100A6 and atrial natriuretic factor in the heart of spontaneously hypertensive rats treated with doxazosin compared to untreated animals. Fragments of heart were collected from five spontaneously hypertensive rats and five spontaneously hypertensive rats receiving doxazosin for six weeks (dose 0.1 mg per 1 kg of body weight). On the paraffin sections S100A6 and atrial natriuretic factor peptides were localized in the heart using immunohistochemistry. Positive immunohistochemical reaction for S100A6 was observed in atrial and ventricular cardiomyocytes and in the coronary vasculature. In the heart of hypertensive rats treated with doxazosin the S100A6 immunoreactivity was significantly lower compared to untreated animals. Immunodetection of atrial natriuretic factor in the heart of rats confirmed presence of peptide in atrial myocardium. Delicate atrial natriuretic factor-immunoreactivity was observed also in few ventricular cardiomyocytes. The atrial natriuretic factor-immunosignal was significantly weaker in hearts of hypertensive rats receiving doxazosin compared to spontaneously hypertensive rats untreated. Since we found that doxazosin reduces the levels of S100A6 and atrial natriuretic factor peptides in the heart of spontaneously hypertensive rats, it can be assumed that cardiovascular disorders that occur in hypertension may be associated with disturbances of cellular processes and signaling pathways.

  3. Influence of doxazosin on biosynthesis of S100A6 and atrial natriuretic factor peptides in the heart of spontaneously hypertensive rats

    PubMed Central

    Piotrowska, Żaneta; Filipek, Anna; Majewski, Mariusz

    2016-01-01

    Hypertension frequently results in severe complications in cardiovascular system and histopathological changes in the heart. To better understand the cellular processes and signaling pathways responsible for the proper functioning of the heart, we decided to check whether doxazosin affects the density of structures containing S100A6 and atrial natriuretic factor in the heart of spontaneously hypertensive rats. The aim of this study is to find differences in the density of the structures containing S100A6 and atrial natriuretic factor in the heart of spontaneously hypertensive rats treated with doxazosin compared to untreated animals. Fragments of heart were collected from five spontaneously hypertensive rats and five spontaneously hypertensive rats receiving doxazosin for six weeks (dose 0.1 mg per 1 kg of body weight). On the paraffin sections S100A6 and atrial natriuretic factor peptides were localized in the heart using immunohistochemistry. Positive immunohistochemical reaction for S100A6 was observed in atrial and ventricular cardiomyocytes and in the coronary vasculature. In the heart of hypertensive rats treated with doxazosin the S100A6 immunoreactivity was significantly lower compared to untreated animals. Immunodetection of atrial natriuretic factor in the heart of rats confirmed presence of peptide in atrial myocardium. Delicate atrial natriuretic factor-immunoreactivity was observed also in few ventricular cardiomyocytes. The atrial natriuretic factor-immunosignal was significantly weaker in hearts of hypertensive rats receiving doxazosin compared to spontaneously hypertensive rats untreated. Since we found that doxazosin reduces the levels of S100A6 and atrial natriuretic factor peptides in the heart of spontaneously hypertensive rats, it can be assumed that cardiovascular disorders that occur in hypertension may be associated with disturbances of cellular processes and signaling pathways. PMID:26515144

  4. Atrial natriuretic peptide regulates lipid mobilization and oxygen consumption in human adipocytes by activating AMPK

    SciTech Connect

    Souza, Sandra C.; Chau, Mary D.L.; Yang, Qing; Gauthier, Marie-Soleil; Clairmont, Kevin B.; Wu, Zhidan; Gromada, Jesper; Dole, William P.

    2011-07-08

    Highlights: {yields} Treatment of differentiated human adipocytes with atrial natriuretic peptide (ANP) increased lipolysis and oxygen consumption by activating AMP-activated protein kinase (AMPK). {yields} ANP stimulated lipid mobilization by selective activation of the alpha2 subunit of AMPK and increased energy utilization through activation of both the alpha1 and alpha2 subunits of AMPK. {yields} ANP enhanced adipocyte mitochondrial oxidative capacity as evidenced by induction of oxidative mitochondrial genes and increase in oxygen consumption. {yields} Exposure of human adipocytes to fatty acids and (TNF{alpha}) induced insulin resistance and decreased expression of mitochondrial genes which was restored to normal by ANP. -- Abstract: Atrial natriuretic peptide (ANP) has been shown to regulate lipid and carbohydrate metabolism providing a possible link between cardiovascular function and metabolism by mediating the switch from carbohydrate to lipid mobilization and oxidation. ANP exerts a potent lipolytic effect via cGMP-dependent protein kinase (cGK)-I mediated-stimulation of AMP-activated protein kinase (AMPK). Activation of the ANP/cGK signaling cascade also promotes muscle mitochondrial biogenesis and fat oxidation. Here we demonstrate that ANP regulates lipid metabolism and oxygen utilization in differentiated human adipocytes by activating the alpha2 subunit of AMPK. ANP treatment increased lipolysis by seven fold and oxygen consumption by two fold, both of which were attenuated by inhibition of AMPK activity. ANP-induced lipolysis was shown to be mediated by the alpha2 subunit of AMPK as introduction of dominant-negative alpha2 subunit of AMPK attenuated ANP effects on lipolysis. ANP-induced activation of AMPK enhanced mitochondrial oxidative capacity as evidenced by a two fold increase in oxygen consumption and induction of mitochondrial genes, including carnitine palmitoyltransferase 1A (CPT1a) by 1.4-fold, cytochrome C (CytC) by 1.3-fold, and

  5. Characterization of atrial natriuretic peptide receptors in brain microvessel endothelial cells

    NASA Technical Reports Server (NTRS)

    Whitson, P. A.; Huls, M. H.; Sams, C. F.

    1991-01-01

    Atrial natriuretic peptide (ANP) binding and ANP-induced increases in cyclic guanosine monophosphate (cGMP) levels have been observed in brain microvessels (Chabrier et al., 1987; Steardo and Nathanson, 1987), suggesting that this fluid-regulating hormone may play a role in the fluid homeostasis of the brain. This study was initiated to characterize the ANP receptors in primary cultures of brain microvessel endothelial cells (BMECs). The apparent equilibrium dissociation constant, Kd, for ANP increased from 0.25 nM to 2.5 nM, and the number of ANP binding sites as determined by Scatchard analysis increased from 7,100 to 170,000 sites/cell between 2 and 10 days of culture following monolayer formation. Time- and concentration-dependent studies on the stimulation of cGMP levels by ANP indicated that guanylate cyclase-linked ANP receptors were present in BMECs. The relative abilities of ANP, brain natriuretic peptide (BNP), and a truncated analog of ANP containing amino acids 5-27 (ANP 5-27) to modulate the accumulation of cGMP was found to be ANP greater than BNP much greater than ANP 5-27. Affinity cross-linking with disuccinimidyl suberate and radiolabeled ANP followed by gel electrophoresis under reducing conditions demonstrated a single band corresponding to the 60-70 kD receptor, indicating the presence of the nonguanylate cyclase-linked ANP receptor. Radiolabeled ANP binding was examined in the presence of various concentrations of either ANP, BNP, or ANP 5-27 and suggested that a large proportion of the ANP receptors present in blood-brain barrier endothelial cells bind all of these ligands similarly. These data indicate both guanylate cyclase linked and nonguanylate cyclase linked receptors are present on BMECs and that a higher proportion of the nonguanylate cyclase linked receptors is expressed. This in vitro culture system may provide a valuable tool for the examination of ANP receptor expression and function in blood-brain barrier endothelial cells.

  6. A- to B-Type Olivine Fabric Transitions Associated with Hydration, Dehydration and Shear Above the Farallon Flat Slab

    NASA Astrophysics Data System (ADS)

    Behr, W. M.; Smith, D.

    2014-12-01

    We investigate mantle rocks associated with hydration, dehydration and shear above the Farallon flat-slab at its contact with the base of North America. The rocks we focus on are ultramafic inclusions hosted within serpentinized ultramafic microbreccia diatremes of the Navajo Volcanic Field (New Mexico) that erupted to the surface at the waning stages of the Laramide orogeny. A large number of petrological and geochronological studies have pinpointed the origin of these rocks to the hydrated mantle wedge above the Farallon slab as well as tectonically eroded and entrained fragments of the plate interface. We combine petrological observations and EBSD measurements of olivine grainsize and LPO to examine the effects of hydration on olivine fabric development in different parts of the supra-subduction zone mantle. The rocks examined include weakly deformed to strongly foliated tectonites we interpret to represent partially hydrated fragments of the upper plate mantle; and mylonites and ultramylonites we interpret to represent deformed fragments of the plate interface. The rocks deformed at temperatures ranging from 500-900°C based on thermometry, and olivine compositions in some record heating just before incorporation in the diatreme mix. We observe the following: Tectonites exhibit A-type bulk olivine LPOs, but show transitions to B-type LPO in local, fine-grained, dynamically recrystallized regions associated with hydrous minerals. Mylonites and ultramylonites with stable chlorite and/or antigorite and recrystallized grainsizes of less than 10μm show strong B-type olivine LPOs. A single mylonite with recrystallized grainsizes of ~35μm shows evidence for prograde metamorphism and dehydration through the chlorite breakdown reaction at temperatures above ~770°C. It contains no hydrous minerals and shows a strong A-type olivine LPO. Together these rocks demonstrate a strong correlation between hydration under high stress conditions, and B-type olivine LPO

  7. The telomeric protein AKTIP interacts with A- and B-type lamins and is involved in regulation of cellular senescence.

    PubMed

    Burla, Romina; Carcuro, Mariateresa; Torre, Mattia La; Fratini, Federica; Crescenzi, Marco; D'Apice, Maria Rosaria; Spitalieri, Paola; Raffa, Grazia Daniela; Astrologo, Letizia; Lattanzi, Giovanna; Cundari, Enrico; Raimondo, Domenico; Biroccio, Annamaria; Gatti, Maurizio; Saggio, Isabella

    2016-08-01

    AKTIP is a shelterin-interacting protein required for replication of telomeric DNA. Here, we show that AKTIP biochemically interacts with A- and B-type lamins and affects lamin A, but not lamin C or B, expression. In interphase cells, AKTIP localizes at the nuclear rim and in discrete regions of the nucleoplasm just like lamins. Double immunostaining revealed that AKTIP partially co-localizes with lamin B1 and lamin A/C in interphase cells, and that proper AKTIP localization requires functional lamin A. In mitotic cells, AKTIP is enriched at the spindle poles and at the midbody of late telophase cells similar to lamin B1. AKTIP-depleted cells show senescence-associated markers and recapitulate several aspects of the progeroid phenotype. Collectively, our results indicate that AKTIP is a new player in lamin-related processes, including those that govern nuclear architecture, telomere homeostasis and cellular senescence.

  8. Evaluation of the retentive force of a b-type Ti-6Mo-4Sn alloy wire clasp.

    PubMed

    Yoda, Nobuhiro; Yokoyama, Masayoshi; Adachi, Genki; Takahashi, Masatoshi; Sasaki, Keiichi

    2010-01-01

    The retentive force of a wire clasp composed of a b-type Ti-6Mo-4Sn alloy (b-Ti alloy) with a low Young modulus was evaluated using a piezoelectric transducer to determine the appropriate undercut for removable partial dentures. There were no significant differences in retentive force between a b-Ti alloy wire with a 0.50-mm undercut and a cobalt-chromium alloy (Co-Cr alloy) wire with a 0.25-mm undercut, or between a b-Ti alloy wire with a 0.75-mm undercut and a Co-Cr alloy wire with a 0.50-mm undercut. The b-Ti alloy wire may be applicable for abutment teeth with a large number of undercuts. Int J Prosthodont 2010;23:38-41.

  9. Isolation and Synthesis of Laxaphycin B-Type Peptides: A Case Study and Clues to Their Biosynthesis.

    PubMed

    Bornancin, Louis; Boyaud, France; Mahiout, Zahia; Bonnard, Isabelle; Mills, Suzanne C; Banaigs, Bernard; Inguimbert, Nicolas

    2015-12-01

    The laxaphyci's B family constitutes a group of five related cyclic lipopeptides isolated from diverse cyanobacteria from all around the world. This group shares a typical structure of 12 amino acids from the l and d series, some of them hydroxylated at the beta position, and all containing a rare beta-amino decanoic acid. Nevertheless, they can be differentiated due to slight variations in the composition of their amino acids, but the configuration of their alpha carbon remains conserved. Here, we provide the synthesis and characterization of new laxaphycin B-type peptides. In doing so we discuss how the synthesis of laxaphycin B and analogues was developed. We also isolate minor acyclic laxaphycins B, which are considered clues to their biosynthesis. PMID:26690181

  10. The telomeric protein AKTIP interacts with A- and B-type lamins and is involved in regulation of cellular senescence

    PubMed Central

    Burla, Romina; Carcuro, Mariateresa; Torre, Mattia La; Fratini, Federica; Crescenzi, Marco; D'Apice, Maria Rosaria; Spitalieri, Paola; Raffa, Grazia Daniela; Astrologo, Letizia; Lattanzi, Giovanna; Cundari, Enrico; Raimondo, Domenico; Biroccio, Annamaria; Gatti, Maurizio

    2016-01-01

    AKTIP is a shelterin-interacting protein required for replication of telomeric DNA. Here, we show that AKTIP biochemically interacts with A- and B-type lamins and affects lamin A, but not lamin C or B, expression. In interphase cells, AKTIP localizes at the nuclear rim and in discrete regions of the nucleoplasm just like lamins. Double immunostaining revealed that AKTIP partially co-localizes with lamin B1 and lamin A/C in interphase cells, and that proper AKTIP localization requires functional lamin A. In mitotic cells, AKTIP is enriched at the spindle poles and at the midbody of late telophase cells similar to lamin B1. AKTIP-depleted cells show senescence-associated markers and recapitulate several aspects of the progeroid phenotype. Collectively, our results indicate that AKTIP is a new player in lamin-related processes, including those that govern nuclear architecture, telomere homeostasis and cellular senescence. PMID:27512140

  11. The telomeric protein AKTIP interacts with A- and B-type lamins and is involved in regulation of cellular senescence.

    PubMed

    Burla, Romina; Carcuro, Mariateresa; Torre, Mattia La; Fratini, Federica; Crescenzi, Marco; D'Apice, Maria Rosaria; Spitalieri, Paola; Raffa, Grazia Daniela; Astrologo, Letizia; Lattanzi, Giovanna; Cundari, Enrico; Raimondo, Domenico; Biroccio, Annamaria; Gatti, Maurizio; Saggio, Isabella

    2016-08-01

    AKTIP is a shelterin-interacting protein required for replication of telomeric DNA. Here, we show that AKTIP biochemically interacts with A- and B-type lamins and affects lamin A, but not lamin C or B, expression. In interphase cells, AKTIP localizes at the nuclear rim and in discrete regions of the nucleoplasm just like lamins. Double immunostaining revealed that AKTIP partially co-localizes with lamin B1 and lamin A/C in interphase cells, and that proper AKTIP localization requires functional lamin A. In mitotic cells, AKTIP is enriched at the spindle poles and at the midbody of late telophase cells similar to lamin B1. AKTIP-depleted cells show senescence-associated markers and recapitulate several aspects of the progeroid phenotype. Collectively, our results indicate that AKTIP is a new player in lamin-related processes, including those that govern nuclear architecture, telomere homeostasis and cellular senescence. PMID:27512140

  12. Isolation and Synthesis of Laxaphycin B-Type Peptides: A Case Study and Clues to Their Biosynthesis

    PubMed Central

    Bornancin, Louis; Boyaud, France; Mahiout, Zahia; Bonnard, Isabelle; Mills, Suzanne C.; Banaigs, Bernard; Inguimbert, Nicolas

    2015-01-01

    The laxaphyci’s B family constitutes a group of five related cyclic lipopeptides isolated from diverse cyanobacteria from all around the world. This group shares a typical structure of 12 amino acids from the l and d series, some of them hydroxylated at the beta position, and all containing a rare beta-amino decanoic acid. Nevertheless, they can be differentiated due to slight variations in the composition of their amino acids, but the configuration of their alpha carbon remains conserved. Here, we provide the synthesis and characterization of new laxaphycin B-type peptides. In doing so we discuss how the synthesis of laxaphycin B and analogues was developed. We also isolate minor acyclic laxaphycins B, which are considered clues to their biosynthesis. PMID:26690181

  13. Isolation and Synthesis of Laxaphycin B-Type Peptides: A Case Study and Clues to Their Biosynthesis.

    PubMed

    Bornancin, Louis; Boyaud, France; Mahiout, Zahia; Bonnard, Isabelle; Mills, Suzanne C; Banaigs, Bernard; Inguimbert, Nicolas

    2015-12-05

    The laxaphyci's B family constitutes a group of five related cyclic lipopeptides isolated from diverse cyanobacteria from all around the world. This group shares a typical structure of 12 amino acids from the l and d series, some of them hydroxylated at the beta position, and all containing a rare beta-amino decanoic acid. Nevertheless, they can be differentiated due to slight variations in the composition of their amino acids, but the configuration of their alpha carbon remains conserved. Here, we provide the synthesis and characterization of new laxaphycin B-type peptides. In doing so we discuss how the synthesis of laxaphycin B and analogues was developed. We also isolate minor acyclic laxaphycins B, which are considered clues to their biosynthesis.

  14. Evaluation of the retentive force of a b-type Ti-6Mo-4Sn alloy wire clasp.

    PubMed

    Yoda, Nobuhiro; Yokoyama, Masayoshi; Adachi, Genki; Takahashi, Masatoshi; Sasaki, Keiichi

    2010-01-01

    The retentive force of a wire clasp composed of a b-type Ti-6Mo-4Sn alloy (b-Ti alloy) with a low Young modulus was evaluated using a piezoelectric transducer to determine the appropriate undercut for removable partial dentures. There were no significant differences in retentive force between a b-Ti alloy wire with a 0.50-mm undercut and a cobalt-chromium alloy (Co-Cr alloy) wire with a 0.25-mm undercut, or between a b-Ti alloy wire with a 0.75-mm undercut and a Co-Cr alloy wire with a 0.50-mm undercut. The b-Ti alloy wire may be applicable for abutment teeth with a large number of undercuts. Int J Prosthodont 2010;23:38-41. PMID:20234890

  15. Plasma Brain-Type Natriuretic Peptide Level Following Seizure and Syncope: Pilot Study

    PubMed Central

    Park, Kyung-Il

    2014-01-01

    Background and Purpose: To explore the clinical feasibility of plasma brain-type natriuretic peptide (proBNP) level to differentiate the two major causes of transient unconsciousness, seizure and vasovagal syncope (VVS) in adult patients. Methods: ProBNP levels were evaluated within 24 hours following attack in patients who had experienced a transient episode of unconsciousness. For confirmatory diagnosis, clinical history was reviewed thoroughly and several work-ups including electroencephalography and cerebral imaging and tilt-table test, were performed in cases of putative VVS, as a part of routine clinical approaches. Results: According to various relevant evaluations, 15 patients were diagnosed as seizure (age, 40.3±13.8 years) and 12 patients were VVS (age, 38.1±17.1 years). Plasma concentrations of pro-BNP were not different between two groups (p=0.714). Median level was 34.3 pg/mL (interquartile range: 12.9–91.1) in post-seizure group and 32.3 pg/mL (interquartile range 8.9–77.4) in post-VVS group. Additionally, it was not correlated with the sampling times within 24 hours after the episodes. Conclusions: The plasma level of pro-BNP has a limited clinical value in differentiating seizure and vasovagal syncope in adults. However, the more validated results with a large population should be sought in the future studies to confirm its value. PMID:24977125

  16. 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.

  17. Doxycycline ameliorates aggregation of collagen and atrial natriuretic peptide in murine post-infarction heart.

    PubMed

    Zhu, Hongjun; Sun, Xianlin; Wang, Deguo; Hu, Nengwei; Zhang, Yao

    2015-05-01

    Heart failure after myocardial infarction (MI) is associated with the aggregation of collagen and some misfolded proteins. This study was aimed to assess the therapeutic efficacy of doxycycline (Dox) in MI-induced heart failure and elucidate the potential mechanisms involved. A heart failure model of animals was established by ligating the left anterior descending coronary artery of rats. The administration of Dox via drinking water (25mg/kg/day) was initiated after surgery and lasted for two weeks. After cardiac function evaluation by echocardiography, all animals were killed to assess the aggregation of type I collagen, atrial natriuretic peptide (ANP), and the activities of matrix metalloproteinases (MMPs), autophagosomes and microtubule-associated protein 1 light chain 3 (LC3). Dox treatment significantly improved cardiac function and attenuated cardiac hypertrophy. Histological observation revealed that Dox significantly reduced the expression of collagen and ANP in the heart. Further investigation showed that Dox significantly inhibited the activities of MMP-2 and MMP-9, increased autophagosomes and enhanced LC3-II in post-infarction hearts. This study revealed that Dox treatment could promote autophagy, reduce ANP aggregation in post-infarction hearts, and inhibit MMP-2 and MMP-9 activities. Dox might act as a potential therapeutic drug for preventing proteotoxicity and cardiac dysfunction.

  18. Differential response of C-type natriuretic peptide to estrogen and dexamethasone in adult bone.

    PubMed

    Prickett, Timothy C R; Wellby, Martin; Barrell, Graham K; Richards, A Mark; Espiner, Eric A

    2014-09-01

    C-type natriuretic peptide (CNP) is crucial in promoting endochondral bone growth in mammals including humans but whether this paracrine hormone participates in maintaining bone integrity in the mature skeleton is unknown. Accordingly we studied changes in plasma and bone tissue CNP in anoestrus adult ewes receiving short term anabolic (estrogen) or catabolic (dexamethasone) treatment for 7days. CNP and the aminoterminal fragment of the CNP prohormone (NTproCNP) were measured in plasma and extracts of cancellous bone excised from vertebral, iliac, tibial and marrow tissues. Concentrations of CNP peptides were much higher in vertebral and iliac extracts than those of tibial or marrow. Both plasma CNP and NTproCNP increased rapidly after estrogen followed by a later rise in bone alkaline phosphatase. Vertebral and iliac (but not tibial or marrow) CNP peptide content were significantly increased by estrogen. Consistent with a skeletal source, plasma NTproCNP was significantly associated with vertebral tissue CNP. In contrast, bone tissue CNP peptide content was unaffected by dexamethasone despite suppression of plasma CNP peptides and bone alkaline phosphatase. We postulate that increases in trabecular bone CNP reflect new endosteal bone formation in these estrogen responsive tissues whereas reduced plasma CNP peptides after dexamethasone, without change in cancellous bone content, reflects reductions in cortical bone turnover.

  19. Constitutively active form of natriuretic peptide receptor 2 ameliorates experimental pulmonary arterial hypertension

    PubMed Central

    Nawa, Nobutoshi; Ishida, Hidekazu; Katsuragi, Shinichi; Baden, Hiroki; Takahashi, Kunihiko; Higeno, Ryota; Torigoe, Fumiko; Mihara, Seiko; Narita, Jun; Miura, Kohji; Nakamura, Kazufumi; Kogaki, Shigetoyo; Ozono, Keiichi

    2016-01-01

    We recently found a constitutively active mutant of natriuretic peptide receptor 2 (caNPR2; V883M), which synthesizes larger amounts of cyclic guanosine monophosphate (cGMP) intracellularly without any ligand stimulation than existing drugs. The aim of this study was to investigate the therapeutic effects of gene transduction using caNPR2 for pulmonary arterial hypertension (PAH). In vitro gene transduction into human pulmonary arterial smooth muscle cells using Sendai virus (SeV) vectors carrying caNPR2 induced 10,000-fold increases in the synthesis of cGMP without ligand stimulation, and the proliferation of caNPR2-expressing cells was significantly attenuated. The PAH model rats generated by hypoxia and the administration of SU5416 were then treated with SeV vectors through a direct injection into the left pulmonary artery. Right ventricular systolic pressure was significantly decreased 2 weeks after the treatment, while systemic blood pressure remained unchanged. Histological analyses revealed that the medial wall thickness and occlusion rate of pulmonary arterioles were significantly improved in caNPR2-treated lungs. Neither the systemic integration of virus vectors nor side effects were observed. The massive stimulation of cGMP synthesis by gene therapy with caNPR2 was safe and effective in a PAH rat model and, thus, has potential as a novel therapy for patients with severe progressive PAH. PMID:27419193

  20. Correlation between heart disorders and concentrations of directly measured atrial natriuretic peptide in plasma.

    PubMed

    Fridrich, L; Szekeres, T; Hartter, E; Schweighofer, F; Gassner, A; Laczkovic, A

    1989-03-01

    We used new commercially available direct radioimmunoassay to measure human atrial natriuretic peptide (h-ANP) in plasma from 48 individuals who were being evaluated for left and right ventricular function. For 13 healthy individuals with normal ventricular function these concentrations ranged up to 54 ng/L. Measurements of h-ANP clearly differentiated between normal subjects, patients with coronary artery disease, and patients who had undergone orthotopic heart transplantation (ANOVA P less than 0.0001, significant differences between all groups)--all showing normal ventricular function at rest. There was a strong negative correlation (r = -0.64, P less than 0.001) between left ventricular ejection fraction and h-ANP concentrations in plasma of patients with proven coronary artery disease, patients with cardiomyopathy, and healthy individuals. Results by the present method and methods involving extraction of the sample correlated well. Evidently the direct assay of h-ANP in plasma yields information that could be used to help evaluate heart disorders and other pathophysiological conditions causing increased h-ANP concentrations in plasma.

  1. Influence of atrial natriuretic factor on fluid efflux from the splenic circulation of the rat.

    PubMed Central

    Deng, Y; Kaufman, S

    1996-01-01

    1. Atrial natriuretic factor (ANF) causes a reduction in plasma volume that is abolished by splenectomy. Experiments were conceived to investigate whether ANF acts within the spleen to increase efflux of fluid from the intravascular to the extravascular space. 2. ANF, infused into the splenic artery of anaesthetized rats at rates of 1, 5 and 20 ng min -1, caused a dose-dependent increase in the arteriovenous difference in haematocrit as blood flowed through the spleen (basal difference, 0.18 +/- 0.10%; difference after 10 min at 20 ng min -1 ANF, 1.5 +/- 0.18%; n = 6). There was no such change in plasma protein concentration. 3. ANF (20 ng min -1) did not alter splenic arterial blood flow. However, splenic venous blood flow fell so that the arteriovenous difference increased significantly (basal difference, 0.34 +/- 0.19 ml min -1; difference at 60 min, 1.1 +/- 0.20 ml min-1, n = 7). There was no change in mean arterial pressure. 4. These data confirm our hypothesis that ANF acts within the spleen to increase fluid efflux from the intravascular to the extravascular space. Since there is no change in total splenic blood flow, we propose that the effects of ANF are mediated by dilatation of the splenic afferent arterioles and constriction of the efferent venules, thus increasing filtration pressure. PMID:9011615

  2. Baseline and post-atrial pacing release of atrial natriuretic factor in mitral stenosis.

    PubMed

    Malatino, L S; Stancanelli, B; Greco, G; Polizzi, G; Leonardi, C; Russo, G; Tamburino, C; Greco, G; Giuffrida, G; Tamburino, G

    1990-01-01

    To investigate the release of atrial natriuretic factor (ANF) in mitral stenosis and the influence of the increase on the frequency of atrial contraction or atrial distention on ANF secretion, we studied 10 patients with symptoms of congestive heart failure (New York Heart Association classes II and III) in sinus rhythm, who were undergoing cardiac catheterization as part of an evaluation workup for mitral stenosis. Echocardiographic tracings, repeat determinations of mean pulmonary artery wedge pressure (MPAWP) and mean right atrial pressure, and blood sampling from the pulmonary artery for measurements of ANF were performed at baseline, during atrial pacing (pacing rate of 125 beats/min for 5 minutes), and 5 minutes after the pacing protocol was completed. Baseline ANF levels were closely related to right atrial pressure (r = 0.89; p less than 0.001) and increased markedly after atrial pacing from 205.6 +/- 39.8 (SEM) to 343.9 +/- 57.9 (SEM) pg/ml. A similar pacing-induced increase was shown for MPAWP and left atrial size. Our data indicate that pacing-induced increases in atrial distention and intracavitary pressure further stimulate release of ANF. However, an independent effect of frequency of atrial pacing on plasma ANF in humans could not be identified. PMID:2136967

  3. Analytical Issues with Natriuretic Peptides – has this been Overly Simplified?

    PubMed Central

    Katrukha, Alexey G.

    2016-01-01

    Natriuretic peptides (NPs) were first described as cardiac biomarkers more than two decades ago. Since that time, numerous studies have confirmed NPs’ diagnostic and prognostic utilities as biomarkers of myocardial function. However, we must now admit that despite the NPs’ relatively long period of use in clinical practice, our understanding of the biochemistry and the variety of circulating forms of NPs, as well as of their potential as biomarkers, remains far from being complete and comprehensive. The highly complex nature and wide diversity of circulating forms of NPs make their accurate measurements in plasma far more complex than initially believed. A highly simplistic view of the NPs’ use is that elevated values of NPs indicate the severity of heart failure and thus reflect the prognosis. However, as shown by a variety of studies, deep understanding of how the NP system works will be required for correct interpretation of test results in routine practice of cardiovascular disease. In this review, we summarize the recent advances in understanding of the complexity of the NP system and discuss related analytical issues, which open new horizons, as well as challenges for clinical diagnostics. PMID:27683533

  4. Genetic Analysis of the Atrial Natriuretic Peptide Gene Polymorphisms among Essential Hypertensive Patients in Malaysia.

    PubMed

    Ghodsian, Nooshin; Ismail, Patimah; Ahmadloo, Salma; Eskandarian, Narges; Etemad, Ali

    2016-01-01

    Background. Atrial natriuretic peptide (ANP) considerably influences blood pressure regulation through water and sodium homoeostasis. Several of the studies have utilized anonymous genetic polymorphic markers and made inconsequent claims about the ANP relevant disorders. Thus, we screened Insertion/Deletion (ID) and G191A polymorphisms of ANP to discover sequence variations with potential functional significance and to specify the linkage disequilibrium pattern between polymorphisms. The relationships of detected polymorphisms with EH with or without Type 2 Diabetes Mellitus (T2DM) status were tested subsequently. Method. ANP gene polymorphisms (I/D and A191G) were specified utilizing mutagenically separated Polymerase Chain Reaction (PCR) in 320 subjects including 163 EH case subjects and 157 controls. Result. This case-control study discovered a significant association between I/D polymorphisms of ANP gene in EH patient without T2DM. However, the study determined no association between G191A polymorphisms of ANP in EH with or without T2DM. In addition, sociodemographic factors in the case and healthy subjects exhibited strong differences (P < 0.05). Conclusion. As a risk factor, ANP gene polymorphisms may affect hypertension. Despite the small sample size in this study, it is the first research assessing the ANP gene polymorphisms in both EH and T2DM patients among Malaysian population. PMID:27413750

  5. Atrial natriuretic peptide stimulates salt secretion by shark rectal gland by releasing VIP

    SciTech Connect

    Silva, P.; Stoff, J.S.; Solomon, R.J.; Lear, S.; Kniaz, D.; Greger, R.; Epstein, F.H.

    1987-01-01

    Salt secretion by the isolated perfused rectal gland of the spiny dogfish shark, Squalus acanthias, is stimulated by synthetic rat atrial natriuretic peptide (ANP II) as well as extracts of shark heart, but not by 8-bromo-cyclic guanosine 5'-monophosphate. Cardiac peptides have no effect on isolated rectal gland cells or perfused tubules, suggesting that stimulation requires an intact gland. The stimulation of secretion by ANP II is eliminated by maneuvers that block neurotransmitter release. Cardiac peptides stimulate the release of vasoactive intestinal peptide (VIP), known to be present in rectal glands nerves, into the venous effluent of perfused glands in parallel with their stimulation of salt secretion, but the release of VIP induced by ANP II is prevented by perfusion with procaine. VIP was measured by radioimmunoassay. Cardiac peptides thus appear to regulate rectal gland secretion by releasing VIP from neural stores within the gland. It is possible that other physiological effects of these hormones might be explained by an action to enhanced local release of neurotransmitters.

  6. Atrial natriuretic factor: radioimmunoassay and effects on adrenal and pituitary glands

    SciTech Connect

    Gutkowska, J.; Horky, K.; Schiffrin, E.L.; Thibault, G.; Garcia, R.; De Lean, A.; Hamet, P.; Tremblay, J.; Anand-Srivastava, M.B.; Januszewicz, P.

    1986-06-01

    A simple and sensitive radioimmunoassay was developed for measurement of immunoreactive atrial natriuretic factor (IR-ANF) in rat and human plasma and in rat atria. The two atria contain about 20 ..mu..g ANF per rat. The right atrium contained 2.5 times more ANF than did the left. Ether anesthesia and morphine markedly increased IR-ANF in rat plasma. The concentration of IR-ANF in plasma of clinically normal human subjects was 65.3 +/- 2.5 pg/ml. Paroxysmal tachycardia and rapid atrial pacing significantly increased IR-ANF in human plasma. Two- to seven-fold higher concentrations were found in coronary sinus blood than in the peripheral circulation. In the plasma of rats and humans, circulating ANF is probably a small-molecular-weight peptide. ANF acts on the adrenal and the pituitary. ANF inhibits aldosterone secretion from rat zona glomerulosa and steroid secretion by bovine adrenal zona glomerulosa and fasciculata. ANF stimulated the basal secretion of arginine vasopressin (AVP) in vitro and inhibited KCl-stimulated release of AVP.

  7. Analytical Issues with Natriuretic Peptides – has this been Overly Simplified?

    PubMed Central

    Katrukha, Alexey G.

    2016-01-01

    Natriuretic peptides (NPs) were first described as cardiac biomarkers more than two decades ago. Since that time, numerous studies have confirmed NPs’ diagnostic and prognostic utilities as biomarkers of myocardial function. However, we must now admit that despite the NPs’ relatively long period of use in clinical practice, our understanding of the biochemistry and the variety of circulating forms of NPs, as well as of their potential as biomarkers, remains far from being complete and comprehensive. The highly complex nature and wide diversity of circulating forms of NPs make their accurate measurements in plasma far more complex than initially believed. A highly simplistic view of the NPs’ use is that elevated values of NPs indicate the severity of heart failure and thus reflect the prognosis. However, as shown by a variety of studies, deep understanding of how the NP system works will be required for correct interpretation of test results in routine practice of cardiovascular disease. In this review, we summarize the recent advances in understanding of the complexity of the NP system and discuss related analytical issues, which open new horizons, as well as challenges for clinical diagnostics.

  8. Atrial natriuretic peptide increases microvascular blood flow and macromolecular escape during renin infusion in the hamster

    SciTech Connect

    Boric, M.P.; Albertini, R. )

    1990-02-01

    The effects of Atrial Natriuretic Peptide (ANP) on microvascular hemodynamics and macromolecular permselectivity were studied in the hamster cheek pouch under resting conditions and during intravenous renin infusion. Fluorescent intravital microscopy was used to observe arteriolar diameters and to detect escape of fluorescent dextran of 150 K-Daltons (FITC-Dx-150). Microvascular plasma flow was estimated by clearance of 51Cr-EDTA and net macromolecular transport by clearance of FITC-Dx-150. At rest, topical ANP (2-250 ng/ml) had no effect on arteriolar diameter, 51Cr-EDTA clearance, relative vascular conductance (RVC) or FITC-Dx-150 clearance. Infusion of renin (10 mU/Kg/Hr, iv) elevated systemic arterial pressure by 30% and reduced cheek pouch RVC by 26%. During renin infusion, topical ANP (50 ng/ml) produced transient arteriolar vasodilation, and increased 51Cr-EDTA clearance (+35%), RVC (+58%) and FITC-Dx-150 clearance (+54%), without affecting systemic pressure. ANP did not induce venular leakage sites under any condition, but changes in FITC-Dx-150 clearance were highly correlated with changes in 51Cr-EDTA clearance, suggesting that the larger macromolecular escape was due to increases in microvascular blood flow and capillary/post-capillary hydrostatic pressure.

  9. Atrial natriuretic peptide receptor heterogeneity and effects on cyclic GMP accumulation

    SciTech Connect

    Leitman, D.C.

    1988-01-01

    The effects of atrial natriuretic peptide (ANP), oxytocin (OT) and vasopressin (AVP) on guanylate cyclase activity and cyclic GMP accumulation were examined, since these hormones appear to be intimately associated with blood pressure and intravascular volume homeostasis. ANP was found to increase cyclic GMP accumulation in ten cell culture systems, which were derived from blood vessels, adrenal cortex, kidney, lung, testes and mammary gland. ANP receptors were characterized in intact cultured cells using {sup 125}I-ANP{sub 8-33}. Specific {sup 125}I-ANP binding was saturable and of high affinity. Scratchard analysis of the binding data for all cell types exhibited a straight line, indicating that these cells possessed a single class of binding sites. Despite the presence of linear Scatchard plots, these studies demonstrated that cultured cells possess two functionally and physically distinct ANP-binding sites. Most of the ANP-binding sites in cultured cells have a molecular size of 66,000 daltons under reducing conditions. The identification of cultured cell types in which hormones (ANP and oxytocin) regulate guanylate cyclase activity and increase cyclic GMP synthesis will provide valuable systems to determine the mechanisms of hormone-receptor coupling to guanylate cyclase and the cellular processes regulated by cyclic GMP.

  10. Differential changes in atrial natriuretic peptide and vasopressin receptor bindings in kidney of spontaneously hypertensive rat

    SciTech Connect

    Ogura, T.; Mitsui, T.; Yamamoto, I.; Katayama, E.; Ota, Z.; Ogawa, N.

    1987-01-19

    To elucidate the role of atrial natriuretic peptide (ANP) and vasopressin (VP) in a hypertensive state, ANP and VP receptor bindings in spontaneously hypertensive rat (SHR) kidney were analyzed using the radiolabeled receptor assay (RRA) technique. Systolic blood pressure of SHR aged 12 weeks was statistically higher than that of age-matched Wistar Kyoto (WKY) rats. Maximum binding capacity (Bmax) of (/sup 125/I)-ANP binding to the SHR kidney membrane preparations was statistically lower than that of WKY rats, but dissociation constant (Kd) was not significantly different. On the other hand, Bmax of (/sup 3/H)-VP binding to the SHR kidney membrane preparations was statistically higher than that of WKY rats, but Kd were similar. Since the physiological action of ANP is natriuresis and VP is the most important antidiuretic hormone in mammalia, these opposite changes of ANP and VP receptor bindings in SHR kidney suggested that these peptides may play an important role in the pathophysiology of the hypertensive state, although it has not been confirmed as yet.

  11. The role of atrial natriuretic peptide (ANP) in cold-induced diuresis (CID)

    SciTech Connect

    Agnew, J.W.; Freund, B.J.; DuBose, D.A.; McKay, J.M.; Hashiro, G.M. Tripler Army Medical Center, Honolulu, HI )

    1991-03-11

    The hormonal control of cold-induced diuresis (CID) remains unresolved. This study investigated the role of ANP, plasma vasopressin (AVP), and aldosterone (ALDO) on CID. Four semi-nude men participated in a 210 min exposure to 15C and 29C air, on separate days. These subjects drank 300 mL of water and had an intravenous saline drip throughout both exposures to replace blood and insensible fluid losses. CID was observed in 15C but not in the 29C experiment, as indicated by a greater urine output. In 15C, atrial natriuretic peptide (ANP) increased after 90 min by 41% and remained elevated for 2 h relative to 29C. No differences were observed in AVP between 15C and 29C. In the 15C versus the 29C experiment, ALDO was approximately 37% lower at the pre, 15 and 90 min time periods. Mean arterial blood pressure was generally greater but only significant at 60 min during the 15C versus the 29C experiment. Urinary NA{sup +} excretion was elevated in 15C relative to 29C while no difference in K{sup +} excretion was observed. Although pressure effects may contribute, the observed natriuresis in the absence of a kaliuresis in the cold suggests a physiological role of ANP in CID.

  12. Involvement of atrial natriuretic peptide in blood pressure reduction induced by estradiol in spontaneously hypertensive rats.

    PubMed

    Belo, Najara O; Silva-Barra, Juliana; Carnio, Evelin C; Antunes-Rodrigues, Jose; Gutkowska, Jolanta; Dos Reis, Adelina M

    2004-01-15

    The aim of the present study was to determine the involvement of atrial natriuretic peptide (ANP) in blood pressure (BP) alterations induced by estradiol treatment. Spontaneously hypertensive rats (SHR) and Wistar rats (WR) were ovariectomized and, after 3 weeks, were injected daily for 4 days with estradiol benzoate (E2; 5 microg/100 g/day) or a vehicle. One day after the last injection, the animals were decapitated, blood was collected, and both right and left atrial appendages were quickly removed for determination of ANP by radioimmunoassay (RIA), or used for ANP mRNA determination. Estradiol treatment induced a significant reduction of blood pressure in SHR, but not in WR. This reduction was correlated with the increase of plasma ANP levels that were significantly increased in E2-treated, compared with vehicle-treated, SHR. E2-treated SHR showed significant increases in ANP concentration in the right and left atria compared to the vehicle-treated animals. These observations were confirmed by ANP mRNA. In summary, the present study shows that short-term estradiol treatment reduces the blood pressure of ovariectomized SHR, but not of WR. This reduction was highly correlated with increased plasma estradiol and ANP levels. These results suggest that ANP is involved in mediating the effect of estradiol on blood pressure reduction.

  13. The potential role of natriuretic peptide-guided management for patients hospitalized for heart failure.

    PubMed

    Maisel, Alan; Xue, Yang; Greene, Stephen J; Pang, Peter S; Januzzi, James L; Piña, Ileana L; DeFilippi, Christopher; Butler, Javed

    2015-03-01

    There are >1 million hospitalizations for heart failure (HF) in the United States annually. After discharge, 25% of these patients are rehospitalized within 30 days, and 30% are dead within 1 year. To date, all trials in patients with acute HF (AHF) have failed to improve post-discharge outcomes. There remains a need for an effective objective risk stratification strategy that is capable of reliably identifying patients at heightened risk for readmission and informing discharge decision making. Natriuretic peptide (NP) levels during and after AHF hospitalization can provide valuable information regarding congestion status and chronic remodeling stress. The lack of sensitivity and inter-rater reliability of physical examination, and failure to achieve dry weight in many patients before discharge, renders the use of NP to guide therapy to prevent readmission an attractive option. NP levels can be used across the spectrum of AHF care settings, ranging from the emergency department and inpatient stay to post-discharge follow-up and chronic management. This review summarizes available data and provides an expert opinion on the potential role of NPs to reduce HF readmissions.

  14. Receptor binding sites for atrial natriuretic factor are expressed by brown adipose tissue

    SciTech Connect

    Bacay, A.C.; Mantyh, C.R.; Vigna, S.R.; Mantyh, P.W. )

    1988-09-01

    To explore the possibility that atrial natriuretic factor (ANF) is involved in thermoregulation we used quantitative receptor autoradiography and homogenate receptor binding assays to identify ANF bindings sites in neonatal rat and sheep brown adipose tissue, respectively. Using quantitative receptor autoradiography were were able to localize high levels of specific binding sites for {sup 125}I-rat ANF in neonatal rat brown adipose tissue. Homogenate binding assays on sheep brown fat demonstrated that the radioligand was binding to the membrane fraction and that the specific binding was not due to a lipophilic interaction between {sup 125}I-rat ANF and brown fat. Specific binding of {sup 125}I-rat ANF to the membranes of brown fat cells was inhibited by unlabeled rat ANF with a Ki of 8.0 x 10(-9) M, but not by unrelated peptides. These studies demonstrate that brown fat cells express high levels of ANF receptor binding sites in neonatal rat and sheep and suggest that ANF may play a role in thermoregulation.

  15. Culture on Electrospun Polyurethane Scaffolds Decreases Atrial Natriuretic Peptide Expression by Cardiomyocytes In Vitro

    PubMed Central

    Rockwood, Danielle N.; Akins, Robert E.; Parrag, Ian; Woodhouse, Kimberly A.; Rabolt, John F.

    2008-01-01

    The function of the mammalian heart depends on the functional alignment of cardiomyocytes, and controlling cell alignment is an important consideration in biomaterial design for cardiac tissue engineering and research. The physical cues that guide functional cell alignment in vitro and the impact of substrate-imposed alignment on cell phenotype, however, are only partially understood. In this report, primary cardiac ventricular cells were grown on electrospun, biodegradable polyurethane (ES-PU) with either aligned or unaligned microfibers. ES-PU scaffolds supported high-density cultures, and cell subpopulations remained intact over two weeks in culture. ES-PU cultures contained electrically-coupled cardiomyocytes with connexin-43 localized to points of cell:cell contact. Multi-cellular organization correlated with microfiber orientation, and aligned materials yielded highly oriented cardiomyocyte groupings. Atrial natriuretic peptide, a molecular marker that has decreasing expression during ventricular cell maturation, was significantly lower in cultures grown on ES-PU scaffolds than in those grown on tissue culture polystyrene. Cells grown on aligned ES-PU had significantly lower steady state levels of ANP and constitutively released less ANP over time indicating that scaffold-imposed cell organization resulted in a shift in cell phenotype to a more mature state. We conclude that the physical organization of microfibers in ES-PU scaffolds impacts both multi-cellular architecture and cardiac cell phenotype in vitro. PMID:18823659

  16. Role of calcium in effects of atrial natriuretic peptide on aldosterone production in adrenal glomerulosa cells

    SciTech Connect

    Chartier, L.; Schiffrin, E.L.

    1987-04-01

    Atrial natriuretic peptide (ANP) inhibits the stimulation of aldosterone secretion by isolated adrenal glomerulosa cells produced by angiotensin II (ANG II), ACTH, and potassium. The effect of ANP on the dose-response curve of aldosterone stimulated by ANG II, ACTH, and potassium on isolated rat adrenal glomerulosa cells was studied. In the presence of ANP the maximal response of aldosterone output stimulated by ANG II or potassium decreased and the half-maximum (EC/sub 50/) of the response to ACTH was displaced to the right. Because these effects resemble those of calcium-channel blockers, the authors investigated the effect of different concentrations of nifedipine, a dihydropyridine calcium-channel blocker, on the dose-response curve of aldosterone stimulated by ANG II, ACTH, and potassium. Nifedipine produced effects similar to ANP. The maximal response of aldosterone stimulated by ANG II and potassium was decreased and the dose-response curve to ACTH was displaced to the right. ANP decreased the maximal response of aldosterone to the dihydropyridine derivative BAY K8644, a calcium-channel activator, without change in its EC/sub 50/. In contrast, nifedipine displaced the dose-response curve to BAY K8644 to the right as expected of a competitive inhibitor. The effect of ANP and nifedipine on basal and stimulated /sup 45/Ca influx into isolated rat adrenal glomerulosa cells was studied. ANP may act on the rat adrenal glomerulosa cells at least in part by interference with calcium entry.

  17. Urinary C-type natriuretic peptide: an emerging biomarker for heart failure and renal remodeling.

    PubMed

    Zakeri, Rosita; Burnett, John C; Sangaralingham, S Jeson

    2015-03-30

    The public health and economic burden of heart failure (HF) is staggering and the need for relevant pathophysiologic and clinical biomarkers to advance the field and improve HF therapy remains high. Renal dysfunction is common among HF patients and is associated with increased HF hospitalization and mortality. It is widely recognized that mechanisms contributing to HF pathogenesis include a complex bidirectional interaction between the kidney and heart, encompassed by the term cardiorenal syndrome (CRS). Among a new wave of urinary biomarkers germane to CRS, C-type natriuretic peptide (CNP) has emerged as an innovative biomarker of renal structural and functional impairment in HF and chronic renal disease states. CNP is a hormone, synthesized in the kidney, and is an important regulator of cell proliferation and organ fibrosis. Hypoxia, cytokines and fibrotic growth factors, which are inherent to both cardiac and renal remodeling processes, are among the recognized stimuli for CNP production and release. In this review we aim to highlight current knowledge regarding the biology and pathophysiological correlates of urinary CNP, and its potential clinical utility as a diagnostic and prognostic biomarker in HF and renal disease states. PMID:25512164

  18. Genetic Analysis of the Atrial Natriuretic Peptide Gene Polymorphisms among Essential Hypertensive Patients in Malaysia

    PubMed Central

    Ghodsian, Nooshin; Ismail, Patimah; Ahmadloo, Salma; Eskandarian, Narges; Etemad, Ali

    2016-01-01

    Background. Atrial natriuretic peptide (ANP) considerably influences blood pressure regulation through water and sodium homoeostasis. Several of the studies have utilized anonymous genetic polymorphic markers and made inconsequent claims about the ANP relevant disorders. Thus, we screened Insertion/Deletion (ID) and G191A polymorphisms of ANP to discover sequence variations with potential functional significance and to specify the linkage disequilibrium pattern between polymorphisms. The relationships of detected polymorphisms with EH with or without Type 2 Diabetes Mellitus (T2DM) status were tested subsequently. Method. ANP gene polymorphisms (I/D and A191G) were specified utilizing mutagenically separated Polymerase Chain Reaction (PCR) in 320 subjects including 163 EH case subjects and 157 controls. Result. This case-control study discovered a significant association between I/D polymorphisms of ANP gene in EH patient without T2DM. However, the study determined no association between G191A polymorphisms of ANP in EH with or without T2DM. In addition, sociodemographic factors in the case and healthy subjects exhibited strong differences (P < 0.05). Conclusion. As a risk factor, ANP gene polymorphisms may affect hypertension. Despite the small sample size in this study, it is the first research assessing the ANP gene polymorphisms in both EH and T2DM patients among Malaysian population. PMID:27413750

  19. In vivo measurement of atrial natriuretic peptide receptors using nuclear imaging.

    PubMed

    Willenbrock, R; Lambert, R; Tremblay, J; Bavaria, G; Langlois, Y; Léveillé, J; Flanagan, R; Hamet, P

    1992-11-01

    We have successfully visualized atrial natriuretic peptide (ANP) receptors in vivo using nuclear imaging. 123I-Labelled ANP, injected in green vervet monkeys, was rapidly bound to ANP receptors in the kidneys and lungs. That the observed uptake was receptor mediated was demonstrated with competition studies using simultaneous injection of unlabelled ANP 99-126. It was possible to distinguish between the ANP receptor subtypes by the use of selective antagonists. Thus coinjection of ANP 102-121-des[Gln, Ser, Gly, Leu, Gly] (C-ANP), an ANP analog that selectively binds to the ANP C-receptor, decreased uptake in the kidneys by 50% but increased relative uptake in the lungs and soft tissues. This method permits for the first time, the dynamic in vivo analysis of ANP receptors and their interaction with endogenous ligand. Differences and changes in local ANP receptor concentrations and occupancy could be detected. Since ANP receptor density and affinity are influenced by various physiological and pathological conditions, clinical and diagnostic applications seem possible.

  20. Role of atrial natriuretic peptide in systemic responses to acute isotonic volume expansion

    NASA Technical Reports Server (NTRS)

    Watenpaugh, Donald E.; Yancy, Clyde W.; Buckey, Jay C.; Lane, Lynda D.; Hargens, Alan R.; Blomqvist, C. G.

    1992-01-01

    A hypothesis is proposed that a temporal relationship exists between increases in cardiac filling pressure and plasma artrial natriuretic peptide (ANP) concentration and also between ANP elevation and vasodilation, fluid movement from plasma to interstitium, and increased urine volume (UV). To test the hypothesis, 30 ml/kg isotonic saline were infused in supine male subjects over 24 min and responses were monitored for 3 h postinfusion. Results show that at end infusion, mean arterial pressure (RAP), heart rate and plasma volume exhibited peak increases of 146, 23, and 27 percent, respectively. Mean plasma ANP and UV peaked (45 and 390 percent, respectively) at 30 min postinfusion. Most cardiovascular variables had returned toward control levels by 1 h postinfusion, and net reabsorption of extravascular fluid ensued. It is concluded that since ANP was not significantly increased until 30 min postinfusion, factors other than ANP initiate responses to intravascular fluid loading. These factors include increased vascular pressures, baroreceptor-mediated vasolidation, and hemodilution of plasma proteins. ANP is suggested to mediate, in part, the renal response to saline infusion.

  1. Circulating serum markers and QRS scar score in Chagas cardiomyopathy.

    PubMed

    Clark, Eva H; Marks, Morgan A; Gilman, Robert H; Fernandez, Antonio B; Crawford, Thomas C; Samuels, Aaron M; Hidron, Alicia I; Galdos-Cardenas, Gerson; Menacho-Mendez, Gilberto Silvio; Bozo-Gutierrez, Ricardo W; Martin, Diana L; Bern, Caryn

    2015-01-01

    Approximately 8 million people have Trypanosoma cruzi infection, and nearly 30% will manifest Chagas cardiomyopathy (CC). Identification of reliable early indicators of CC risk would enable prioritization of treatment to those with the highest probability of future disease. Serum markers and electrocardiogram (EKG) changes were measured in 68 T. cruzi-infected individuals in various stages of cardiac disease and 17 individuals without T. cruzi infection or cardiac disease. T. cruzi-infected individuals were assigned to stage A (normal EKG/chest x-ray [CXR]), B (abnormal EKG/normal CXR), or C (abnormal EKG/cardiac structural changes). Ten serum markers were measured using enzyme-linked immunosorbent assay (ELISA)/Luminex, and QRS scores were calculated. Higher concentrations of transforming growth factor-β1 (TGFβ1), and TGFβ2 were associated with stage B compared with stage A. Matrix Metalloproteinase 2 (MMP2), Tissue Inhibitors of MMP 1, QRS score, and Brain Natriuretic Protein rose progressively with increasing CC severity. Elevated levels of several markers of cardiac damage and inflammation are seen in early CC and warrant additional evaluation in longitudinal studies.

  2. Circulating Serum Markers and QRS Scar Score in Chagas Cardiomyopathy

    PubMed Central

    Clark, Eva H.; Marks, Morgan A.; Gilman, Robert H.; Fernandez, Antonio B.; Crawford, Thomas C.; Samuels, Aaron M.; Hidron, Alicia I.; Galdos-Cardenas, Gerson; Menacho-Mendez, Gilberto Silvio; Bozo-Gutierrez, Ricardo W.; Martin, Diana L.; Bern, Caryn

    2015-01-01

    Approximately 8 million people have Trypanosoma cruzi infection, and nearly 30% will manifest Chagas cardiomyopathy (CC). Identification of reliable early indicators of CC risk would enable prioritization of treatment to those with the highest probability of future disease. Serum markers and electrocardiogram (EKG) changes were measured in 68 T. cruzi-infected individuals in various stages of cardiac disease and 17 individuals without T. cruzi infection or cardiac disease. T. cruzi-infected individuals were assigned to stage A (normal EKG/chest x-ray [CXR]), B (abnormal EKG/normal CXR), or C (abnormal EKG/cardiac structural changes). Ten serum markers were measured using enzyme-linked immunosorbent assay (ELISA)/Luminex, and QRS scores were calculated. Higher concentrations of transforming growth factor-β1 (TGFβ1), and TGFβ2 were associated with stage B compared with stage A. Matrix Metalloproteinase 2 (MMP2), Tissue Inhibitors of MMP 1, QRS score, and Brain Natriuretic Protein rose progressively with increasing CC severity. Elevated levels of several markers of cardiac damage and inflammation are seen in early CC and warrant additional evaluation in longitudinal studies. PMID:25385865

  3. The VLT-FLAMES Tarantula Survey. XVIII. Classifications and radial velocities of the B-type stars

    NASA Astrophysics Data System (ADS)

    Evans, C. J.; Kennedy, M. B.; Dufton, P. L.; Howarth, I. D.; Walborn, N. R.; Markova, N.; Clark, J. S.; de Mink, S. E.; de Koter, A.; Dunstall, P. R.; Hénault-Brunet, V.; Maíz Apellániz, J.; McEvoy, C. M.; Sana, H.; Simón-Díaz, S.; Taylor, W. D.; Vink, J. S.

    2015-02-01

    We present spectral classifications for 438 B-type stars observed as part of the VLT-FLAMES Tarantula Survey (VFTS) in the 30 Doradus region of the Large Magellanic Cloud. Radial velocities are provided for 307 apparently single stars, and for 99 targets with radial-velocity variations which are consistent with them being spectroscopic binaries. We investigate the spatial distribution of the radial velocities across the 30 Dor region, and use the results to identify candidate runaway stars. Excluding potential runaways and members of two older clusters in the survey region (SL 639 and Hodge 301), we determine a systemic velocity for 30 Dor of 271.6 ± 12.2 kms-1 from 273 presumed single stars. Employing a 3σ criterion we identify nine candidate runaway stars (2.9% of the single stars with radial-velocity estimates). The projected rotational velocities of the candidate runaways appear to be significantly different to those of the full B-type sample, with a strong preference for either large (≥345 kms-1) or small (≤65 kms-1) rotational velocities. Of the candidate runaways, VFTS 358 (classified B0.5: V) has the largest differential radial velocity (-106.9 ± 16.2 kms-1), and a preliminary atmospheric analysis finds a significantly enriched nitrogen abundance of 12 + log (N/H) ≳ 8.5. Combined with a large rotational velocity (vesini = 345 ± 22 kms-1), this is suggestive of past binary interaction for this star. Table 7 and Appendix A are available in electronic form at http://www.aanda.org

  4. Identification of a mouse B-type cyclin which exhibits developmentally regulated expression in the germ line

    NASA Technical Reports Server (NTRS)

    Chapman, D. L.; Wolgemuth, D. J.

    1992-01-01

    To begin to examine the function of cyclins in mammalian germ cells, we have screened an adult mouse testis cDNA library for the presence of B-type cyclins. We have isolated cDNAs that encode a murine B-type cyclin, which has been designated cycB1. cycB1 was shown to be expressed in several adult tissues and in the midgestation mouse embryo. In the adult tissues, the highest levels of cycB1 transcripts were seen in the testis and ovary, which contain germ cells at various stages of differentiation. The major transcripts corresponding to cycB1 are 1.7 and 2.5 kb, with the 1.7 kb species being the predominant testicular transcript and the 2.5 kb species more abundant in the ovary. Examination of cDNAs corresponding to the 2.5 kb and 1.7 kb mRNAs revealed that these transcripts encode identical proteins, differing only in the polyadenylation signal used and therefore in the length of their 3' untranslated regions. Northern blot and in situ hybridization analyses revealed that the predominant sites of cycB1 expression in the testis and ovary were in the germinal compartment, particularly in early round spermatids in the testis and growing oocytes in the ovary. Thus cycB1 is expressed in both meiotic and postmeiotic cells. This pattern of cycB1 expression further suggests that cycB1 may have different functions in the two cell types, only one of which correlates with progression of the cell cycle.

  5. New elements in the C-type natriuretic peptide signaling pathway inhibiting swine in vitro oocyte meiotic resumption.

    PubMed

    Santiquet, Nicolas; Papillon-Dion, Emilie; Djender, Nadjib; Guillemette, Christine; Richard, François J

    2014-07-01

    C-type natriuretic peptide (CNP) and its cognate receptor, natriuretic peptide receptor (NPR) B, have been shown to promote cGMP production in granulosa/cumulus cells. Once transferred to the oocyte through the gap junctions, the cGMP inhibits oocyte meiotic resumption. CNP has been shown to bind another natriuretic receptor, NPR-C. NPR-C is known to interact with and degrade bound CNP, and has been reported to possess signaling functions. Therefore, NPR-C could participate in the control of oocyte maturation during swine in vitro maturation (IVM). Here, we examine the effect of CNP signaling on meiotic resumption, the amount of cGMP and gap junctional communication (GJC) regulation during swine IVM. The results show an inhibitory effect of CNP in inhibiting oocyte meiotic resumption in follicle-stimulating hormone (FSH)-stimulated IVM. We also found that an NPR-C-specific agonist (cANP([4-23])) is likely to play a role in maintaining meiotic arrest during porcine IVM when in the presence of a suboptimal dose of CNP. Moreover, we show that, even if CNP can increase intracellular concentration of cGMP in cumulus-oocyte complexes, cANP((4-23)) had no impact on cGMP concentration, suggesting a potential cGMP-independent signaling pathway related to NPR-C activation. These data support a potential involvement of cANP((4-23)) through NPR-C in inhibiting oocyte meiotic resumption while in the presence of a suboptimal dose of CNP. The regulation of GJC was not altered by CNP, cANP((4-23)), or the combination of CNP and cANP((4-23)), supporting their potential contribution in sending signals to the oocytes. These findings offer promising insights in to new elements of the signaling pathways that may be involved in inhibiting resumption of meiosis during FSH-stimulated swine IVM.

  6. C-type natriuretic peptide inhibits leukocyte recruitment and platelet-leukocyte interactions via suppression of P-selectin expression

    NASA Astrophysics Data System (ADS)

    Scotland, Ramona S.; Cohen, Marc; Foster, Paul; Lovell, Matthew; Mathur, Anthony; Ahluwalia, Amrita; Hobbs, Adrian J.

    2005-10-01

    The multifaceted process of immune cell recruitment to sites of tissue injury is key to the development of an inflammatory response and involved in the pathogenesis of numerous cardiovascular disorders. We recently identified C-type natriuretic peptide (CNP) as an important endothelium-derived mediator that regulates vascular tone and protects against myocardial ischemia/reperfusion injury. Herein, we investigated whether CNP inhibits leukocyte recruitment and platelet aggregation and thereby exerts a potential antiinflammatory influence on the blood vessel wall. We assessed the effects of CNP on leukocyte-endothelial cell interactions in mouse mesenteric postcapillary venules in vivo in animals with high basal leukocyte activation (endothelial nitric oxide synthase knockout mice, eNOS-/-) or under acute inflammatory conditions (induced by interleukin-1 or histamine). CNP suppressed basal leukocyte rolling in eNOS-/- mice in a rapid, reversible, and concentration-dependent manner. These effects of CNP were mimicked by the selective natriuretic peptide receptor-C agonist cANF4-23. CNP also suppressed leukocyte rolling induced by IL-1 or histamine, inhibited platelet-leukocyte interactions, and prevented thrombin-induced platelet aggregation of human blood. Furthermore, analysis of human umbilical vein endothelial cells, leukocytes, and platelets revealed that CNP selectively attenuates expression of P-selectin. Thus, CNP is a modulator of acute inflammation in the blood vessel wall characterized by leukocyte and platelet activation. These antiinflammatory effects appear to be mediated, at least in part, via suppression of P-selectin expression. These observations suggest that endothelial CNP might maintain an anti-atherogenic influence on the blood vessel wall and represent a target for therapeutic intervention in inflammatory cardiovascular disorders. endothelium | natriuretic peptide receptor type C | atherosclerosis | thrombosis

  7. Correlation between brain natriuretic peptide levels and the prognosis of patients with left ventricular diastolic dysfunction

    PubMed Central

    GONG, HUI; WANG, XIN; SHI, YI-JUN; SHANG, WEN-JING; LING, YI; PAN, LI-JIAN; SHI, HAI-MING

    2016-01-01

    The present study aimed to investigate the association between brain natriuretic peptide (BNP) levels and the prognosis of patients with left ventricular (LV) diastolic dysfunction. A total of 708 inpatients with cardiovascular disease (mean age, 66 years; 395 males and 313 females) were grouped according to initial BNP and were followed-up for 20–51 months (average, 30.86 months) until endpoint events occurred. Endpoints were defined as mortality or readmission due to cardiovascular disease, or mortality due to any other reason. A total of 67 and 77 events were reported in the BNP ≤80 pg/ml and BNP >80 pg/ml groups, respectively. The occurrence rate of the endpoint was significantly higher in the BNP >80 pg/ml group, as compared with the BNP ≤80 pg/ml group (26.28 vs. 16.14%; relative risk=1.63). Furthermore, the durations of patient survival were significantly shorter in the BNP >80 pg/ml group, as compared with the BNP ≤80 pg/ml group (P=0.0006), and patient survival decreased as BNP levels rose (P=0.0074). Among the 708 patients, 677 underwent echocardiographic detection at the same time. No significant correlation was detected between BNP levels and survival time in 178 patients with normal LV diastolic function [mitral Doppler flow, early diastolic (E)/late diastolic (A)>1] (P=0.2165); whereas a negative correlation was determined in 499 patients with LVD dysfunction (E/A≤1) (Spearman's rho=−0.0899; P=0.0447). The prognoses of patients with elevated BNP levels were correspondingly worse in the present study and these correlations were demonstrated to be significant in patients with LV diastolic dysfunction. Therefore, BNP levels may be used to predict the prognosis of patients with cardiovascular disease. PMID:27313677

  8. Effect of phorbol ester on the release of atrial natriuretic peptide from the hypertrophied rat myocardium.

    PubMed Central

    Kinnunen, P.; Taskinen, T.; Järvinen, M.; Ruskoaho, H.

    1991-01-01

    1. To determine the cellular mechanisms of atrial natriuretic peptide (ANP) release from ventricular cardiomyocytes, the secretory and the cardiac effects of a phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), known to stimulate protein kinase C activity in heart cells, were studied in isolated, perfused heart preparations from 2- and 21-month-old Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. TPA was added to the perfusion fluid for 30 min at a concentration of 46 nM after removal of atrial tissue. Additionally, atrial and ventricular levels of immunoreactive ANP (IR-ANP) and ANP mRNA, the distribution of ANP within ventricles as well as the relative contribution of atria and ventricles in the release of ANP were studied. 2. Ventricular hypertrophy that gradually developed in hypertensive rats resulted in remarkable augmentation of ANP gene expression, as reflected by elevated levels of immunoreactive ANP and ANP mRNA. The total amount of IR-ANP in the ventricles of the SHR rats increased 41 fold and ANP mRNA levels 12.9 fold from the age of 2 to 21 months. At the age of 21 months, levels of IR-ANP and ANP mRNA in the ventricles of SHR rats were 5.4 fold and 3.7 fold higher, respectively, than in the normotensive WKY rats. Immunohistochemical studies demonstrated ANP granules within the hypertrophic ventricles of the old SHR rats, but not within normal ventricular tissue. 3. In isolated perfused heart preparations, the severely hypertrophied ventricular tissue of SHR rats after atrialectomy secreted more ANP into the perfusate than did the control hearts.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 2 PMID:1826618

  9. Adipose tissue natriuretic peptide receptor expression is related to insulin sensitivity in obesity and diabetes

    PubMed Central

    Kovacova, Zuzana; Tharp, William G.; Liu, Dianxin; Wei, Wan; Xie, Hui

    2016-01-01

    Objective Cardiac natriuretic peptides (NPs) bind to two receptors (NPRA‐mediator of signaling; NPRC‐clearance receptor) whose ratio, NPRR (NPRA/NPRC), determines the NP bioactivity. This study investigated the relationship of NP receptor gene expression in adipose tissue and muscle with obesity and glucose intolerance. Prospectively, the study also assessed whether changes in NP receptor expression and thermogenic gene markers accompanied improvements of insulin sensitivity. Methods A cross‐sectional study of subjects with a wide range of BMI and glucose tolerance (n = 50) was conducted, as well as a randomized 12‐week trial of subjects with type 2 diabetes mellitus (T2DM) treated with pioglitazone (n = 9) or placebo (n = 10). Results NPRR mRNA was significantly lower in adipose tissue of subjects with obesity when compared with lean subjects (P ≤ 0.001). NPRR decreased with progression from normal glucose tolerance to T2DM (P < 0.01) independently of obesity. Treatment of subjects with T2DM with pioglitazone increased NPRR in adipose tissue (P ≤ 0.01) in conjunction with improvements in insulin sensitivity and increases of the thermogenic markers PPARγ coactivator‐1α and uncoupling protein 1 (P ≤ 0.01). Conclusions Decreased adipose tissue NPRR was associated with obesity, glucose intolerance, and insulin resistance. This relationship was not observed for skeletal muscle NPRR. Pharmacological improvement of insulin sensitivity in subjects with T2DM was tied to improvement in NPRR and increased expression of genes involved in thermogenic processes. PMID:26887289

  10. Use of brain natriuretic Peptide and bioimpedance to guide therapy in heart failure patients.

    PubMed

    Valle, Roberto; Aspromonte, Nadia

    2010-01-01

    The key management goals for the stabilization of patients admitted for acutely decompensated heart failure (ADHF) include relief of congestion and restoration of hemodynamic stability. Nevertheless, in spite of clinical improvement, many patients are discharged with hemodynamic congestion. In response to volume expansion, the heart secretes the brain natriuretic peptide (BNP) with a biological action that counter-regulates the activation of the renin-angiotensin-aldosterone system. Since BNP is released by increased volume load and wall stretch, and declines after treatment with drugs of proven efficacy, on the basis of an improvement in filling pressures the level of BNP has been proposed as a 'measure' of congestion. The BNP level of a patient who is admitted with ADHF comprises two components: a baseline, euvolemic 'dry' BNP level and a level induced by volume or pressure overload ('wet' BNP level). So, the prognostic value of BNP during hospitalization depends on the time of measurement: from the lowest on admission when congestion is present (wet BNP) to the highest on clinical and instrumental stability (dry BNP), following the achievement of normohydration, as determined by fluid volume measurement. Euvolemia can be set as the primary goal of treatment for ADHF with dry BNP concentration as a target for discharge other than improvement of symptoms, because high BNP levels predict rehospitalization and death. Discharge criteria utilizing both BNP and hydration status measurement which account for the heterogeneity of the patient population and incorporate different strategies of care should be developed. This could in the next future offer an aid in monitoring heart failure patients or actively guiding optimal titration of therapy. PMID:20428005

  11. [Four-week simulated weightlessness increases the expression of atrial natriuretic peptide in the myocardium].

    PubMed

    Zhang, Wen-Cheng; Lu, Yuan-Ming; Yang, Huai-Zhang; Xu, Peng-Tao; Chang, Hui; Yu, Zhi-Bin

    2013-04-25

    One of the major circulatory changes that occur in human during space flight and simulated weightlessness is a cerebral redistribution of body fluids, which is accompanied by an increase of blood volume in the upper body. Therefore, atrial myocardium should increase the secretion of atrial natriuretic peptide (ANP), but the researches lack common conclusion until now. The present study was to investigate the expression level of ANP in simulated weightlessness rats, and to confirm the changes of ANP by observing the associated proteins of soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). The tail-suspended rat model was used to simulate weightlessness. Western blots were carried out to examine the expression levels of ANP and SNARE proteins in atrial and left ventricular myocardium. The results showed that ANP expression in atrial myocardium showed an increase in 4-week tail-suspended rats (SUS) compared with that in the synchronous control rats (CON). We only detected a trace amount of ANP in the left ventricular myocardium of the CON, but found an enhanced expression of ANP in left ventricular myocardium of the SUS. Expression of VAMP-1/2 (vesicle associated SNARE) increased significantly in both atrial and left ventricular myocardium in the SUS compared with that in the CON. There was no difference of the expression of syntaxin-4 (target compartment associated SNARE) between the CON and SUS, but the expression of SNAP-23 showed an increase in atrial myocardium of the SUS compared with that in the CON. Synip and Munc-18c as regulators of SNAREs did not show significant difference between the CON and SUS. These results suggest that the expression of ANP shows an increase in atrial and left ventricular myocardium of 4-week tail-suspended rats. Enhanced expression of VAMP-1/2 associated with ANP vesicles confirms the increased expression of ANP in atrial and left ventricular myocardium.

  12. Plant natriuretic peptides induce proteins diagnostic for an adaptive response to stress

    PubMed Central

    Turek, Ilona; Marondedze, Claudius; Wheeler, Janet I.; Gehring, Chris; Irving, Helen R.

    2014-01-01

    In plants, structural and physiological evidence has suggested the presence of biologically active natriuretic peptides (PNPs). PNPs are secreted into the apoplast, are systemically mobile and elicit a range of responses signaling via cGMP. The PNP-dependent responses include tissue specific modifications of cation transport and changes in stomatal conductance and the photosynthetic rate. PNP also has a critical role in host defense responses. Surprisingly, PNP-homologs are produced by several plant pathogens during host colonization suppressing host defense responses. Here we show that a synthetic peptide representing the biologically active fragment of the Arabidopsis thaliana PNP (AtPNP-A) induces the production of reactive oxygen species in suspension-cultured A. thaliana (Col-0) cells. To identify proteins whose expression changes in an AtPNP-A dependent manner, we undertook a quantitative proteomic approach, employing tandem mass tag (TMT) labeling, to reveal temporal responses of suspension-cultured cells to 1 nM and 10 pM PNP at two different time-points post-treatment. Both concentrations yield a distinct differential proteome signature. Since only the higher (1 nM) concentration induces a ROS response, we conclude that the proteome response at the lower concentration reflects a ROS independent response. Furthermore, treatment with 1 nM PNP results in an over-representation of the gene ontology (GO) terms “oxidation-reduction process,” “translation” and “response to salt stress” and this is consistent with a role of AtPNP-A in the adaptation to environmental stress conditions. PMID:25505478

  13. The relation between intraocular pressure change and plasma natriuretic peptide under simulated hypobaric conditions

    PubMed Central

    Karadag, Remzi; Sen, Ahmet; Yildirim, Nilgun; Basmak, Hikmet; Golemez, Haydar; Cakir, Erdinc; Akin, Ahmet

    2010-01-01

    Purpose: To ascertain whether the changes in intraocular pressure (IOP) that occur during hypobaric hypoxic exposure are related to plasma N-terminal pro-brain natriuretic peptide (BNP) levels. Materials and Methods: The study group comprised 26 healthy participants (all male, mean age 23.1 years). IOP was measured at local ground level, (792 m above sea level), then while in a chamber providing hypobaric hypoxic conditions (the subjects were exposed to a pressure equivalent to 9144 m for 1-3 min), and again after exit from the chamber. In each condition, the mean of three consecutive measurements of IOP was calculated for each eye. For BNP measurements, blood samples were drawn before the participants entered the chamber and just after they left the chamber. Results: IOP during hypobaric hypoxic exposure (18.00 ± 3.70 mmHg) was significantly greater than that before (15.66 ± 2.10 mmHg, P < 0.001) or after (16.10 ± 2.63 mmHg, P = 0.001) the exposure. IOP levels before and after the exposure were not significantly different (P = 0.136). Plasma BNP levels measured before and after exposure to hypobaric hypoxic conditions were not significantly different (P = 0.462). Conclusion: Plasma BNP levels did not change after short-term hypobaric hypoxic exposure, while the IOP increased. This increase may have been caused by some other systemic factors. As the hypobaric hypoxic conditions were reversed, IOP decreased to normal levels. PMID:20413920

  14. 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

  15. Clearance function of type C receptors of atrial natriuretic factor in rats

    SciTech Connect

    Almeida, F.A.; Suzuki, M.; Scarborough, R.M.; Lewicki, J.A.; Maack, T.

    1989-02-01

    The overwhelming majority of atrial natriuretic factor (ANF) receptors in kidney and vascular tissues do not mediate any of the known functional effects of the hormone. To test whether these receptors (C-ANF receptors) function as clearance receptors for circulating ANF-(1-28), we determined the effects of C-ANF-(4-23) (des(Gln18Ser19Gly20Leu21Gly22)rANF-(3-23)-NH2), a specific ligand of C-ANF receptors, on the pharmacokinetics and hydrolysis of 125I-labeled ANF-(1-28) in anesthetized rats. Radioactivity in plasma was characterized by trichloroacetic acid solubility and high-pressure liquid chromatography. C-ANF-(4-23) (1 and 10 micrograms.min-1.kg body wt-1) led to marked dose-dependent increases in initial plasma concentration of administered 125I-ANF-(1-28) and decreases in its volume of distribution at steady state (Vss), metabolic clearance rate (MCR), and appearance of hydrolytic products ((125I)monoiodotyrosine and free 125I) in plasma (Pm). At the highest dose, C-ANF-(4-23) decreased Vss from 97 +/- 12 to 36 +/- 2 ml/100 g body wt, MCR from 50 +/- 4 to 12 +/- 1 ml.min-1.100 g body wt-1, and Pm from 54 +/- 8 to 11 +/- 2% of initial plasma 125I-ANF-(1-28). The data demonstrate that C-ANF receptors are mainly responsible for the very large volume of distribution and fast MCR of ANF in the rat. In this manner, C-ANF receptors are likely to play an important role in the homeostasis of circulating ANF.

  16. B‐type natriuretic peptide identifies silent myocardial ischaemia in stroke survivors

    PubMed Central

    Wong, K Y K; McSwiggan, S; Kennedy, N S J; MacWalter, R S; Struthers, A D

    2006-01-01

    Objective To test the hypothesis that B‐type natriuretic peptide (BNP) predicts reversible myocardial ischaemia in stroke survivors who do not have chest pain or previous myocardial infarction. Methods 56 stroke survivors (mean (SE) age 68 (8) years) underwent tetrofosmin myocardial perfusion scanning with dipyridamole as the stressor. The degree of ischaemia was assessed by a scoring system (out of 64) by an experienced observer blinded to the results of BNP. Results In the whole cohort, BNP was significantly correlated with the degree of myocardial ischaemia on stress scanning (Spearman's r  =  −0.475, p < 0.001). BNP also correlated with the degree of reversible ischaemia (stress score − rest score; Spearman's r  =  0.28, two tailed p  =  0.049). In the cohort who did not have left ventricular systolic dysfunction (n  =  44), BNP remained higher in patients with relevant myocardial ischaemia (mean (SE) BNP 20.9 pg/ml, 95% confidence interval (CI) 15.2 to 26.5 v 12.2 pg/ml, 95% CI 5.95 to 18.5; p  =  0.046); 33 of the 44 patients had no chest pain or history of myocardial infarction. The relation between resting BNP and both inducible ischaemia and dipyridamole stress score remained significant (Spearman's r  =  0.37 and −0.38, respectively). Conclusions BNP correlates with the degree of reversible myocardial ischaemia in patients who do not have chest pain or a history of myocardial infarction or evidence of left ventricular systolic dysfunction. Stroke survivors with a high BNP deserve further investigations to rule out significant reversible myocardial ischaemia, in order to reduce their risk of cardiac death. PMID:16216865

  17. The Origin of Olivine B-Type Fabric in Naturally Deformed Peridotite: Insight from the Ronda Large-Scale Mantle Shear Zone (spain)

    NASA Astrophysics Data System (ADS)

    Précigout, J.; Hirth, G.

    2011-12-01

    Strain-induced olivine Lattice Preferred Orientation (LPO) mostly controls the propagation of seismic waves in the mantle. Hence, it strongly affects the imaging of mantle structures through analyzing of elastic waves coming from deep earthquakes (Ismaïl and Mainprice, 1998). Understanding the relationships between mantle deformation and olivine LPO is thus crucial to objectively interpret the deep mantle structures. Here, based on detailed documentation of olivine LPOs in the Ronda peridotite (southern Spain), we provide evidences of flow-normal a-axis LPO, i.e., B-type fabric, within a kilometer-scale ductile shear zone. This fabric occurs upon entering the shear zone and describes a progressive transition from A-type fabric (parallel-flow a-axis LPO) to B-type fabric. While B-type fabrics have been described from several localities, to our knowledge this is the first olivine fabric transition ever observed in naturally deformed peridotites. Furthermore, while the olivine fabric strength (Jindex) increases in the A-type fabric domain towards the center of the shear zone, the Jindex progressively decreases in the B-type fabric domain. Based on deformation experiments, A-type fabric occurs during high-temperature/low-stress deformation of anhydrous olivine aggregates (Jung and Karato, 2001). In contrast, the B-type fabrics have been observed under a wide range of conditions: 1) at high-temperature/low stress conditions in the presence of melt (Kohlstedt and Holtzman, 2009); 2) at high-stress in the presence of water (Jung and Karato, 2001); 3) under dry conditions at very high pressure (> 3 GPa; Jung et al., 2009); and 4) during diffusion-creep in the presence of orthopyroxene (Sundberg and Cooper, 2008). In our natural example, we conclude that the B-type fabric arises from enhancing diffusion creep at the expense of dislocation creep, because: 1) the B-type fabric is observed to overprint the typical fabric of anhydrous peridotite (A-type), 2) the Ronda

  18. Pulsations in B-type supergiants with masses M<20 M_{⊙} before and after core helium ignition

    NASA Astrophysics Data System (ADS)

    Ostrowski, J.; Daszyńska-Daszkiewicz, J.

    2015-03-01

    Evolutionary tracks and pulsational analysis of models with masses of 13-18 M⊙ are presented. We address two important questions. The first one deals with one of the most unresolved problems in astrophysics, i.e. the existence of a blue loop after core helium ignition; the so-called to loop or not to loop problem. We show that inward overshooting from the outer convective zone in the red giant phase is prerequisite for the development of the blue loop. Our second question concerns pulsational instability of models in the core helium burning phase. We present for the first time that models on the blue loop can have unstable modes driven by the κ mechanism operating in the Z-bump. Contrary to post-main-sequence models in the shell hydrogen burning phases, pulsational instability of the blue loop models depends mainly on effective temperature and metallicity is of secondary importance. Finally, we try to interpret the oscillation spectrum of the blue supergiant HD 163899, the only member of the slowly pulsating B-type supergiant class and to get some clue on the evolutionary status of the star.

  19. Improvement of enantioselectivity of the B-type halohydrin hydrogen-halide-lyase from Corynebacterium sp. N-1074.

    PubMed

    Watanabe, Fumiaki; Yu, Fujio; Ohtaki, Akashi; Yamanaka, Yasuaki; Noguchi, Keiichi; Odaka, Masafumi; Yohda, Masafumi

    2016-09-01

    Halohydrin hydrogen-halide-lyase (H-Lyase) is a bacterial enzyme involved in the degradation of halohydrins. This enzyme catalyzes the intramolecular nucleophilic displacement of a halogen by a vicinal hydroxyl group in halohydrins, producing the corresponding epoxides. The H-Lyases have been classified into A, B and C subtypes based on amino acid sequence similarities. These enzymes have attracted much attention as industrial catalysts in the synthesis of chiral chemicals from prochiral halohydrins. In the present study, we constructed mutants of B-type H-Lyase from Corynebacterium sp. N-1074 (HheB) displaying higher enantioselectivity by structure-based site-directed mutagenesis and random mutagenesis. A triple mutant of HheB exhibited 98.5% enantioselectivity, the highest ever reported, toward (R)-4-chloro-3-hydroxy-butyronitrile production, with the yield reaching approximately two-fold that of the wild-type enzyme. We discuss the structural basis of the high enantioselectivity and productivity of the mutant by comparing the crystal structures of the mutant HheB and the wild-type enzyme in complex with or without the substrate analogue.

  20. Improvement of enantioselectivity of the B-type halohydrin hydrogen-halide-lyase from Corynebacterium sp. N-1074.

    PubMed

    Watanabe, Fumiaki; Yu, Fujio; Ohtaki, Akashi; Yamanaka, Yasuaki; Noguchi, Keiichi; Odaka, Masafumi; Yohda, Masafumi

    2016-09-01

    Halohydrin hydrogen-halide-lyase (H-Lyase) is a bacterial enzyme involved in the degradation of halohydrins. This enzyme catalyzes the intramolecular nucleophilic displacement of a halogen by a vicinal hydroxyl group in halohydrins, producing the corresponding epoxides. The H-Lyases have been classified into A, B and C subtypes based on amino acid sequence similarities. These enzymes have attracted much attention as industrial catalysts in the synthesis of chiral chemicals from prochiral halohydrins. In the present study, we constructed mutants of B-type H-Lyase from Corynebacterium sp. N-1074 (HheB) displaying higher enantioselectivity by structure-based site-directed mutagenesis and random mutagenesis. A triple mutant of HheB exhibited 98.5% enantioselectivity, the highest ever reported, toward (R)-4-chloro-3-hydroxy-butyronitrile production, with the yield reaching approximately two-fold that of the wild-type enzyme. We discuss the structural basis of the high enantioselectivity and productivity of the mutant by comparing the crystal structures of the mutant HheB and the wild-type enzyme in complex with or without the substrate analogue. PMID:27215832

  1. Myocardin-Related Transcription Factor A Is a Common Mediator of Mechanical Stress- and Neurohumoral Stimulation-Induced Cardiac Hypertrophic Signaling Leading to Activation of Brain Natriuretic Peptide Gene Expression▿ †

    PubMed Central

    Kuwahara, Koichiro; Kinoshita, Hideyuki; Kuwabara, Yoshihiro; Nakagawa, Yasuaki; Usami, Satoru; Minami, Takeya; Yamada, Yuko; Fujiwara, Masataka; Nakao, Kazuwa

    2010-01-01

    Subjecting cardiomyocytes to mechanical stress or neurohumoral stimulation causes cardiac hypertrophy characterized in part by reactivation of the fetal cardiac gene program. Here we demonstrate a new common mechanism by which these stimuli are transduced to a signal activating the hypertrophic gene program. Mechanically stretching cardiomyocytes induced nuclear accumulation of myocardin-related transcription factor A (MRTF-A), a coactivator of serum response factor (SRF), in a Rho- and actin dynamics-dependent manner. Expression of brain natriuretic peptide (BNP) and other SRF-dependent fetal cardiac genes in response to acute mechanical stress was blunted in mice lacking MRTF-A. Hypertrophic responses to chronic pressure overload were also significantly attenuated in mice lacking MRTF-A. Mutation of a newly identified, conserved and functional SRF-binding site within the BNP promoter, or knockdown of MRTF-A, reduced the responsiveness of the BNP promoter to mechanical stretch. Nuclear translocation of MRTF-A was also involved in endothelin-1- and angiotensin-II-induced activation of the BNP promoter. Moreover, mice lacking MRTF-A showed significantly weaker hypertrophic responses to chronic angiotensin II infusion than wild-type mice. Collectively, these findings point to nuclear translocation of MRTF-A as a novel signaling mechanism mediating both mechanical stretch- and neurohumoral stimulation-induced BNP gene expression and hypertrophic responses in cardiac myocytes. PMID:20606005

  2. Lack of association between serum paraoxonase-1 activity and residual platelet aggregation during dual anti-platelet therapy.

    PubMed

    Ohmori, Tsukasa; Yano, Yuichiro; Sakata, Asuka; Ikemoto, Tomokazu; Shimpo, Masahisa; Madoiwa, Seiji; Katsuki, Takaaki; Mimuro, Jun; Shimada, Kazuyuki; Kario, Kazuomi; Sakata, Yoichi

    2012-04-01

    High residual platelet aggregability during thienopyridine treatment occurs because of low levels of the active drug metabolite, and is associated with an increased rate of major adverse cardiovascular events. Recent findings suggest that paraoxonase-1 (PON1) is a major determinant for clopidogrel efficacy. The aim of this study was to assess the impact of serum PON1 activity on platelet aggregability in thienopyridine-treated patients. In 72 patients receiving treatment with aspirin and ticlopidine after acute coronary syndrome, various laboratory data including the formation of platelet aggregations induced by agonists were compared with serum PON1 activities, measured as paraoxonase and homocysteine thiolactone hydrolase (HTLase). Serum paraoxonase activity was significantly associated with HTLase activity (R=0.4487, P<0.0001). These PON1 activities were not correlated with any parameters for platelet aggregation, hypertension, sleep apnea, and diabetes mellitus. In contrast, serum PON1 activities seemed to be involved in cardiac function, with brain natriuretic peptide and ejection fraction being significantly correlated with serum HTLase activity (R=-0.2767, P=0.0214) and paraoxonase activity (R=0.2558, P=0.0339), respectively. Paraoxonase activity also demonstrated a significant association with increased levels of ankle-brachial index (R=0.267, P=0.0255). Serum PON1 activities did not influence platelet aggregability during treatment with thienopyridine. However, they might modulate cardiac function after acute coronary syndrome and progression of atherosclerosis. PMID:22115701

  3. Comparison of treatment effects of bevantolol and metoprolol on cardiac function and natriuretic peptides in patients with dilated cardiomyopathy.

    PubMed

    Hara, Yuji; Hamada, Mareomi; Ohtsuka, Tomoaki; Ogimoto, Akiyoshi; Saeki, Hideyuki; Matsunaka, Tsuyoshi; Suzuki, Jun; Shigematsu, Yuji

    2002-12-01

    This study was designed to compare the efficacy of bevantolol, a beta(1)-selective blocker with alpha-blockade and vasodilating activity, with that of metoprolol, a beta(1)-selective receptor blocker, for the treatment of idiopathic dilated cardiomyopathy (DCM). Forty-one patients with DCM were enrolled to receive either bevantolol or metoprolol in addition to the standard therapy for DCM. They were classified into two groups: 16 patients were treated with bevantolol and 25 were treated with metoprolol. Echocardiographic parameters and atrial and brain natriuretic peptides (ANP, BNP) were measured before treatment and after 6 months of treatment. Left ventricular dimension at end-diastole and end-systole was significantly lower and fractional shortening was significantly higher after treatment than before treatment in both groups. The plasma ANP and BNP levels were significantly decreased in both groups. Changes in all variables, except for systolic blood pressure, showed no significant differences between the two groups. In conclusion, bevantolol showed parallel beneficial effects to those of metoprolol on cardiac function and natriuretic peptides in patients with DCM.

  4. Cloning and sequence analysis of an Ophiophagus hannah cDNA encoding a precursor of two natriuretic peptide domains.

    PubMed

    Lei, Weiwei; Zhang, Yong; Yu, Guoyu; Jiang, Ping; He, Yingying; Lee, Wenhui; Zhang, Yun

    2011-04-01

    The king cobra (Ophiophagus hannah) is the largest venomous snake. Despite the components are mainly neurotoxins, the venom contains several proteins affecting blood system. Natriuretic peptide (NP), one of the important components of snake venoms, could cause local vasodilatation and a promoted capillary permeability facilitating a rapid diffusion of other toxins into the prey tissues. Due to the low abundance, it is hard to purify the snake venom NPs. The cDNA cloning of the NPs become a useful approach. In this study, a 957 bp natriuretic peptide-encoding cDNA clone was isolated from an O. hannah venom gland cDNA library. The open-reading frame of the cDNA encodes a 210-amino acid residues precursor protein named Oh-NP. Oh-NP has a typical signal peptide sequence of 26 amino acid residues. Surprisingly, Oh-NP has two typical NP domains which consist of the typical sequence of 17-residue loop of CFGXXDRIGC, so it is an unusual NP precursor. These two NP domains share high amino acid sequence identity. In addition, there are two homologous peptides of unknown function within the Oh-NP precursor. To our knowledge, Oh-NP is the first protein precursor containing two NP domains. It might belong to another subclass of snake venom NPs. PMID:21334357

  5. Cloning and sequence analysis of an Ophiophagus hannah cDNA encoding a precursor of two natriuretic peptide domains.

    PubMed

    Lei, Weiwei; Zhang, Yong; Yu, Guoyu; Jiang, Ping; He, Yingying; Lee, Wenhui; Zhang, Yun

    2011-04-01

    The king cobra (Ophiophagus hannah) is the largest venomous snake. Despite the components are mainly neurotoxins, the venom contains several proteins affecting blood system. Natriuretic peptide (NP), one of the important components of snake venoms, could cause local vasodilatation and a promoted capillary permeability facilitating a rapid diffusion of other toxins into the prey tissues. Due to the low abundance, it is hard to purify the snake venom NPs. The cDNA cloning of the NPs become a useful approach. In this study, a 957 bp natriuretic peptide-encoding cDNA clone was isolated from an O. hannah venom gland cDNA library. The open-reading frame of the cDNA encodes a 210-amino acid residues precursor protein named Oh-NP. Oh-NP has a typical signal peptide sequence of 26 amino acid residues. Surprisingly, Oh-NP has two typical NP domains which consist of the typical sequence of 17-residue loop of CFGXXDRIGC, so it is an unusual NP precursor. These two NP domains share high amino acid sequence identity. In addition, there are two homologous peptides of unknown function within the Oh-NP precursor. To our knowledge, Oh-NP is the first protein precursor containing two NP domains. It might belong to another subclass of snake venom NPs.

  6. Proton Transfer in the K-Channel Analog of B-Type Cytochrome c Oxidase from Thermus thermophilus

    PubMed Central

    Woelke, Anna Lena; Wagner, Anke; Galstyan, Gegham; Meyer, Tim; Knapp, Ernst-Walter

    2014-01-01

    A key enzyme in aerobic metabolism is cytochrome c oxidase (CcO), which catalyzes the reduction of molecular oxygen to water in the mitochondrial and bacterial membranes. Substrate electrons and protons are taken up from different sides of the membrane and protons are pumped across the membrane, thereby generating an electrochemical gradient. The well-studied A-type CcO uses two different entry channels for protons: the D-channel for all pumped and two consumed protons, and the K-channel for the other two consumed protons. In contrast, the B-type CcO uses only a single proton input channel for all consumed and pumped protons. It has the same location as the A-type K-channel (and thus is named the K-channel analog) without sharing any significant sequence homology. In this study, we performed molecular-dynamics simulations and electrostatic calculations to characterize the K-channel analog in terms of its energetic requirements and functionalities. The function of Glu-15B as a proton sink at the channel entrance is demonstrated by its rotational movement out of the channel when it is deprotonated and by its high pKA value when it points inside the channel. Tyr-244 in the middle of the channel is identified as the valve that ensures unidirectional proton transfer, as it moves inside the hydrogen-bond gap of the K-channel analog only while being deprotonated. The electrostatic energy landscape was calculated for all proton-transfer steps in the K-channel analog, which functions via proton-hole transfer. Overall, the K-channel analog has a very stable geometry without large energy barriers. PMID:25418102

  7. NLTE carbon abundance determination in selected A- and B-type stars and the interpretation of C I emission lines

    NASA Astrophysics Data System (ADS)

    Alexeeva, S. A.; Ryabchikova, T. A.; Mashonkina, L. I.

    2016-10-01

    We constructed a comprehensive model atom for C I-C II using the most up-to-date atomic data available and evaluated the non-local thermodynamic equilibrium (NLTE) line formation for C I and C II in classical 1D models representing the atmospheres of A- and late B-type stars. Our NLTE calculations predict the emission that appears at effective temperature of 9250 to 10 500 K depending on log g in the C I 8335, 9405 Å singlet lines and at Teff> 15 000 K (log g = 4) in the C I 9061-9111 Å, 9603-9658 Å triplet lines. A pre-requisite of the emission phenomenon is the overionization-recombination mechanism resulting in a depopulation of the lower levels of C I to a greater extent than the upper levels. Extra depopulation of the lower levels of the transitions corresponding to the near-infrared lines, is caused by photon loss in the UV lines C I 2479, 1930, and 1657 Å. We analysed the lines of C I and C II in Vega, HD 73666, Sirius, 21 Peg, π Cet, HD 22136, and ι Her taking advantage of their observed high-resolution spectra. The C I emission lines were detected in the four hottest stars, and they were well reproduced in our NLTE calculations. For each star, the mean NLTE abundances from lines of the two ionization stages, C I and C II, including the C I emission lines, were found to be consistent. We show that the predicted C I emission phenomenon depends strongly on whether accurate or approximate electron-impact excitation rates are applied.

  8. Expression and regulation of scavenger receptor class B type 1 in the rat ovary and uterus during the estrous cycle.

    PubMed

    Wang, Yalei; Meng, Chenling; Wei, Quanwei; Shi, Fangxiong; Mao, Dagan

    2015-04-01

    Scavenger receptor class B type 1 (SR-B1) preferentially mediates the selective uptake of high density lipoprotein-cholesterol ester and the delivery of cholesterol for steroidogenesis. Although multiple analyses have investigated the function of SR-B1 in the liver, adrenal and ovary, its expression in rat ovary and uterus during the estrous cycle is lacking. In the present study, real-time PCR, western blot and immunohistochemistry (IHC) were used to investigate SR-B1 expression in the rat ovary and uterus during the estrous cycle. The results demonstrated that ovarian SR-B1 expression was in a stage-dependent manner, continuously increased from proestrus and kept elevated during metoestrus, while uterine SR-B1 expression decreased from proestrus to diestrus. To determine whether ovarian and uterine SR-B1 expression were affected by sex steroid hormones, immature rats were treated with 17 β-estradiol (E2), progesterone (P4), or their antagonists from postnatal days 24-26. Results showed that the levels of SR-B1 mRNA and protein were significantly up-regulated by E2 in both the ovary and uterus. IHC results showed that SR-B1 was primarily localized in the oocytes, theca internal cells (T-I) of follicles, interstitial cells (IC) as well as corpus luteum (CL), but not granulosa cells (GC) in the ovary during the estrous cycle. Uterine SR-B1 was highly expressed in the endometrial luminal epithelial cells (LEC) and glandular epithelial cells (GEC) as well as in the circular muscle (CM) cells, and weak staining in stromal cells (SC) through estrous cycle. Taken together, SR-B1 expression in the ovary and uterus across the estrous cycle demonstrate that SR-B1 may be involved in uterine function, follicular development as well as luteal function.

  9. Oxygen abundance determination of B-type stars with the O I 7771-5 Å lines*

    NASA Astrophysics Data System (ADS)

    Takeda, Yoichi; Honda, Satoshi

    2016-06-01

    Oxygen abundances of 34 B-type stars in the effective temperature range of Teff ˜ 10000-28000 K with diversified rotational velocities (vesin i ˜ 0-250 km s-1) were determined from the O I triplet lines at 7771-5 Å, with an aim of examining whether this O I feature can be a reliable abundance indicator for such high-temperature stars including rapid rotators. It revealed that the required non-local thermodynamic equilibrium (LTE) abundance correction is distinctly large (ranging from ˜-0.6 dex to ˜-1.7 dex) and its consideration is indispensable. On the condition that the non-LTE effect is taken into account, this triplet is a useful O abundance indicator (with a precision of ≲ 0.2 dex) up to Teff ≲ 25000 K, since its total equivalent width is sufficiently large ( ≳ 200 mÅ). In contrast, it is not adequate for abundance derivation for stars at Teff ≳ 25000 K, where its strength rapidly drops down toward a hardly detectable level (except for sharp-lined stars) and its sensitivity to Teff or log g becomes considerably large. The resulting non-LTE oxygen abundances turned out to be almost normal (i.e., near-solar around ˜8.7-8.8 within ˜±0.2 dex) for most stars without any dependence upon projected rotational velocity as well as luminosity (or mass), which is consistent with the prediction of recent stellar evolution calculations.

  10. Proton transfer in the K-channel analog of B-type Cytochrome c oxidase from Thermus thermophilus.

    PubMed

    Woelke, Anna Lena; Wagner, Anke; Galstyan, Gegham; Meyer, Tim; Knapp, Ernst-Walter

    2014-11-01

    A key enzyme in aerobic metabolism is cytochrome c oxidase (CcO), which catalyzes the reduction of molecular oxygen to water in the mitochondrial and bacterial membranes. Substrate electrons and protons are taken up from different sides of the membrane and protons are pumped across the membrane, thereby generating an electrochemical gradient. The well-studied A-type CcO uses two different entry channels for protons: the D-channel for all pumped and two consumed protons, and the K-channel for the other two consumed protons. In contrast, the B-type CcO uses only a single proton input channel for all consumed and pumped protons. It has the same location as the A-type K-channel (and thus is named the K-channel analog) without sharing any significant sequence homology. In this study, we performed molecular-dynamics simulations and electrostatic calculations to characterize the K-channel analog in terms of its energetic requirements and functionalities. The function of Glu-15B as a proton sink at the channel entrance is demonstrated by its rotational movement out of the channel when it is deprotonated and by its high pKA value when it points inside the channel. Tyr-244 in the middle of the channel is identified as the valve that ensures unidirectional proton transfer, as it moves inside the hydrogen-bond gap of the K-channel analog only while being deprotonated. The electrostatic energy landscape was calculated for all proton-transfer steps in the K-channel analog, which functions via proton-hole transfer. Overall, the K-channel analog has a very stable geometry without large energy barriers.

  11. Water exit pathways and proton pumping mechanism in B-type cytochrome c oxidase from molecular dynamics simulations.

    PubMed

    Yang, Longhua; Skjevik, Åge A; Han Du, Wen-Ge; Noodleman, Louis; Walker, Ross C; Götz, Andreas W

    2016-09-01

    Cytochrome c oxidase (CcO) is a vital enzyme that catalyzes the reduction of molecular oxygen to water and pumps protons across mitochondrial and bacterial membranes. While proton uptake channels as well as water exit channels have been identified for A-type CcOs, the means by which water and protons exit B-type CcOs remain unclear. In this work, we investigate potential mechanisms for proton transport above the dinuclear center (DNC) in ba3-type CcO of Thermus thermophilus. Using long-time scale, all-atom molecular dynamics (MD) simulations for several relevant protonation states, we identify a potential mechanism for proton transport that involves propionate A of the active site heme a3 and residues Asp372, His376 and Glu126(II), with residue His376 acting as the proton-loading site. The proposed proton transport process involves a rotation of residue His376 and is in line with experimental findings. We also demonstrate how the strength of the salt bridge between residues Arg225 and Asp287 depends on the protonation state and that this salt bridge is unlikely to act as a simple electrostatic gate that prevents proton backflow. We identify two water exit pathways that connect the water pool above the DNC to the outer P-side of the membrane, which can potentially also act as proton exit transport pathways. Importantly, these water exit pathways can be blocked by narrowing the entrance channel between residues Gln151(II) and Arg449/Arg450 or by obstructing the entrance through a conformational change of residue Tyr136, respectively, both of which seem to be affected by protonation of residue His376. PMID:27317965

  12. Serum bactericidal test.

    PubMed Central

    Stratton, C W

    1988-01-01

    The serum bactericidal test represents one of the few in vitro tests performed in the clinical microbiology laboratory that combines the interaction of the pathogen, the antimicrobial agent, and the patient. Although the use of such a test antedates the antimicrobial era, its performance, results, and interpretation have been subject to question and controversy. Much of the confusion concerning the serum bactericidal test can be avoided by an understanding of the various factors which influence bactericidal testing. In addition, the methodologic aspects of the serum bactericidal test have recently been addressed and should place this test on firmer ground. New information on the clinical utility of this test is becoming available; additional data are needed to establish more clearly the usefulness of the serum bactericidal test in specific infections. Such clinical trials from multiple centers will enable firmer recommendations for the future use of the serum bactericidal test. PMID:3060242

  13. Perioperative application of N-terminal pro-brain natriuretic peptide in patients undergoing cardiac surgery

    PubMed Central

    2013-01-01

    Background The purpose of the research was to find out the factors which influence plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, then to assess whether preoperative plasma NT-proBNP levels could predict postoperative outcomes of cardiac surgery. Methods Between November 2008 and February 2010,225 patients who underwent cardiac surgery in our department were included in the study. The mean age was 61.25 ± 12.54 years, and 156 (69.3%) patients were male. NT-proBNP, CK-MB, cTnT and creatinine levels were measured preoperatively and 24 hours after operation. Postoperatively outcomes including ventilation time, length of stay in ICU and hospital, and mortality were closely monitored. The endpoints includes: 1) use of inotropic agents or intra-aortic balloon pump ≥24 h; 2) creatinine level elevated to hemodialysis; 3) cardiac events; 4) ICU stay ≥5d; 5) ventilation dependence ≥ 72 h; 6) deaths within 30 days of surgery. Results NT-proBNP concentrations (median [interquartile range]) increased from 728.4 pg/ml (IQR 213.5 to 2551 pg/ml) preoperatively to 1940.5 pg/ml (IQR 995.9 to 3892 pg/ml) postoperatively (P = 0.015). Preoperative atrial fibrillation, NYHA class III/IV, ejection fraction, pulmonary arterial pressure, left ventricle end-diastolic diameter (LVEDD), preoperative plasma creatinine and cTnT levels were significantly associated with preoperative NT-proBNP levels in univariate analysis. The preoperative NT-proBNP was closely related to ventilation time (P = 0.009), length of stay in ICU (P = 0.004) and length of stay in hospital (P = 0.019). Receiver operating characteristic curves demonstrated a cut-off value above 2773.5 pg/ml was the best cutoff (sensitivity of 63.6% and specificity of 80.8%) to predict the mortality within 30d of surgery. Conclusions Preoperative plasma NT-proBNP level presents a high individual variability in patients undergoing cardiac surgery. NYHA classification, ejection

  14. B-type receptor for platelet-derived growth factor mediates a chemotactic response by means of ligand-induced activation of the receptor protein-tyrosine kinase.

    PubMed Central

    Westermark, B; Siegbahn, A; Heldin, C H; Claesson-Welsh, L

    1990-01-01

    Porcine aorta endothelial cells are devoid of receptors for platelet-derived growth factor (PDGF). We have transfected such cells with cDNA for the PDGF B-type receptor, both the wild-type receptor and a mutant form of the receptor (K634A), in which the putative nucleotide-binding lysine of the protein-tyrosine domain has been changed to alanine. Immunoprecipitation studies of metabolically labeled cells showed that both types of receptors were synthesized and processed to the mature form of Mr 190,000. In cells expressing the wild-type receptor, PDGF-BB, the natural ligand for the B-type receptor, induced membrane ruffling and reorganization of actin. Such a response has previously been seen in cells expressing the natural PDGF B-type receptor in response to PDGF-BB. No such effect was induced in nontransfected cells or in cells expressing the K634A mutant receptor. PDGF was also shown to be chemotactic for cells expressing the wild-type receptor, whereas no chemotactic response was elicited in control cells or in cells expressing the K634A mutant receptor. Our study thus provides formal evidence that the PDGF B-type receptor mediates a motility response including actin reorganization and chemotaxis. Furthermore, the results establish a role for the receptor-associated protein-tyrosine kinase in the transduction of the chemotactic signal. Images PMID:2153283

  15. The B-type Channel Is a Major Route for Iron Entry into the Ferroxidase Center and Central Cavity of Bacterioferritin*

    PubMed Central

    Wong, Steve G.; Grigg, Jason C.; Le Brun, Nick E.; Moore, Geoffrey R.; Murphy, Michael E. P.; Mauk, A. Grant

    2015-01-01

    Bacterioferritin is a bacterial iron storage and detoxification protein that is capable of forming a ferric oxyhydroxide mineral core within its central cavity. To do this, iron must traverse the bacterioferritin protein shell, which is expected to occur through one or more of the channels through the shell identified by structural studies. The size and negative electrostatic potential of the 24 B-type channels suggest that they could provide a route for iron into bacterioferritin. Residues at the B-type channel (Asn-34, Glu-66, Asp-132, and Asp-139) of E. coli bacterioferritin were substituted to determine if they are important for iron core formation. A significant decrease in the rates of initial oxidation of Fe(II) at the ferroxidase center and subsequent iron mineralization was observed for the D132F variant. The crystal structure of this variant shows that substitution of residue 132 with phenylalanine caused a steric blockage of the B-type channel and no other material structural perturbation. We conclude that the B-type channel is a major route for iron entry into both the ferroxidase center and the iron storage cavity of bacterioferritin. PMID:25512375

  16. Serum and Glucocorticoid Regulated Kinase 1 in Sodium Homeostasis

    PubMed Central

    Lou, Yiyun; Zhang, Fan; Luo, Yuqin; Wang, Liya; Huang, Shisi; Jin, Fan

    2016-01-01

    The ubiquitously expressed serum and glucocorticoid regulated kinase 1 (SGK1) is tightly regulated by osmotic and hormonal signals, including glucocorticoids and mineralocorticoids. Recently, SGK1 has been implicated as a signal hub for the regulation of sodium transport. SGK1 modulates the activities of multiple ion channels and carriers, such as epithelial sodium channel (ENaC), voltage-gated sodium channel (Nav1.5), sodium hydrogen exchangers 1 and 3 (NHE1 and NHE3), sodium-chloride symporter (NCC), and sodium-potassium-chloride cotransporter 2 (NKCC2); as well as the sodium-potassium adenosine triphosphatase (Na+/K+-ATPase) and type A natriuretic peptide receptor (NPR-A). Accordingly, SGK1 is implicated in the physiology and pathophysiology of Na+ homeostasis. Here, we focus particularly on recent findings of SGK1’s involvement in Na+ transport in renal sodium reabsorption, hormone-stimulated salt appetite and fluid balance and discuss the abnormal SGK1-mediated Na+ reabsorption in hypertension, heart disease, edema with diabetes, and embryo implantation failure. PMID:27517916

  17. Serum and Glucocorticoid Regulated Kinase 1 in Sodium Homeostasis.

    PubMed

    Lou, Yiyun; Zhang, Fan; Luo, Yuqin; Wang, Liya; Huang, Shisi; Jin, Fan

    2016-01-01

    The ubiquitously expressed serum and glucocorticoid regulated kinase 1 (SGK1) is tightly regulated by osmotic and hormonal signals, including glucocorticoids and mineralocorticoids. Recently, SGK1 has been implicated as a signal hub for the regulation of sodium transport. SGK1 modulates the activities of multiple ion channels and carriers, such as epithelial sodium channel (ENaC), voltage-gated sodium channel (Nav1.5), sodium hydrogen exchangers 1 and 3 (NHE1 and NHE3), sodium-chloride symporter (NCC), and sodium-potassium-chloride cotransporter 2 (NKCC2); as well as the sodium-potassium adenosine triphosphatase (Na⁺/K⁺-ATPase) and type A natriuretic peptide receptor (NPR-A). Accordingly, SGK1 is implicated in the physiology and pathophysiology of Na⁺ homeostasis. Here, we focus particularly on recent findings of SGK1's involvement in Na⁺ transport in renal sodium reabsorption, hormone-stimulated salt appetite and fluid balance and discuss the abnormal SGK1-mediated Na⁺ reabsorption in hypertension, heart disease, edema with diabetes, and embryo implantation failure. PMID:27517916

  18. Circumstellar discs in Galactic centre clusters: Disc-bearing B-type stars in the Quintuplet and Arches clusters

    NASA Astrophysics Data System (ADS)

    Stolte, A.; Hußmann, B.; Olczak, C.; Brandner, W.; Habibi, M.; Ghez, A. M.; Morris, M. R.; Lu, J. R.; Clarkson, W. I.; Anderson, J.

    2015-06-01

    We investigate the circumstellar disc fraction as determined from L-band excess observations of the young, massive Arches and Quintuplet clusters residing in the central molecular zone of the Milky Way. The Quintuplet cluster was searched for L-band excess sources for the first time. We find a total of 26 excess sources in the Quintuplet cluster, and 21 sources with L-band excesses in the Arches cluster, of which 13 are new detections. With the aid of proper motion membership samples, the disc fraction of the Quintuplet cluster could be derived for the first time to be 4.0 ± 0.7%. There is no evidence for a radially varying disc fraction in this cluster. In the case of the Arches cluster, a disc fraction of 9.2 ± 1.2% approximately out to the cluster's predicted tidal radius, r< 1.5 pc, is observed. This excess fraction is consistent with our previously found disc fraction in the cluster in the radial range 0.3 B-type stars, 2

  19. Serum globulin electrophoresis

    MedlinePlus

    ... may indicate: Acute infection Bone marrow cancer called multiple myeloma Chronic inflammatory disease (for example, rheumatoid arthritis and ... test Hemoglobin Hyperimmunization Immunoelectrophoresis - ... electrophoresis - serum Rheumatoid arthritis Systemic lupus erythematosus ...

  20. Serum free hemoglobin test

    MedlinePlus

    Blood hemoglobin; Serum hemoglobin ... Hemoglobin (Hb) is the main component of red blood cells. It is a protein that carries oxygen. ... people may contain up to 5 mg/dL hemoglobin. Normal value ranges may vary slightly among different ...

  1. Evidence for a further stimulation of atrial natriuretic factor release by atrial pacing in patients with mitral stenosis.

    PubMed

    Malatino, L S; Stancanelli, B; Greco, G; Polizzi, G; Leonardi, C; Russo, G; Tamburino, C; Greco, G; Giuffrida, G; Tamburino, G

    1989-12-01

    To investigate the release of atrial natriuretic factor (ANF) in mitral stenosis and the effect of an increased atrial contraction frequency on atrial distension and ANF secretion, we studied 14 patients [New York Heart Association (NYHA) grades II-III] in sinus rhythm, undergoing cardiac catheterization for mitral stenosis. Echocardiographic tracings, repeat determinations of mean pulmonary artery wedge pressure and blood samples from the pulmonary artery for ANF measurements were taken at baseline, during atrial pacing (125 beats/min for 5 min) and 5 min after pacing. After pacing, ANF levels rose markedly with a parallel increase in mean pulmonary artery wedge pressure and left atrial size. These data indicate that atrial pacing is capable of further stimulating ANF release, even in patients with elevated baseline ANF and left atrial pressure and an increased left atrial dimension. PMID:2534411

  2. Increased atrial natriuretic peptide (6-33) binding sites in the subfornical organ of water deprived and Brattleboro rats

    SciTech Connect

    Saavedra, J.M.; Israel, A.; Correa, F.M.A.; Kurihara, M.

    1986-09-01

    Binding sites for rat atrial natriuretic eptide (6-33) (ANP) were quantitated in the subfornical organ of chronically dehydrated homozygous Brattleboro rats unable to synthesize vasopressin; heterozygous Brattleboro rats, their controls, Long Evans rats and Long Evans rats after 4 days of water deprivation. Brain sections were incubated in the presence of /sup 125/I-ANP and the results analyzed by autoradiography coupled to computerized microdensitometry and comparison to /sup 125/I-standards. Brattleboro rats and water deprived Long Evans rats presented a higher number of ANP binding sites than their normally hydrated controls. The results suggest a role of ANP binding sites in the subfornical organ in the central regulation of fluid balance and vasopressin secretion.

  3. Alpha-human atrial natriuretic polypeptide (. cap alpha. -hANP) specific binding sites in bovine adrenal gland

    SciTech Connect

    Higuchi, K.; Nawata, H.; Kato, K.I.; Ibayashi, H.; Matsuo, H.

    1986-06-13

    The effects of synthetic ..cap alpha..-human atrial natriuretic polypeptide (..cap alpha..-hANP) on steroidogenesis in bovine adrenocortical cells in primary monolayer culture were investigated. ..cap alpha..-hANP did not inhibit basal aldosterone secretion. ..cap alpha..-hANP induced a significant dose-dependent inhibition of basal levels of cortisol and dehydroepiandrosterone (DHEA) secretion and also of aCTH (10/sup -8/M)-stimulated increases in aldosterone, cortisol and DHEA secretion. Visualization of (/sup 125/I) ..cap alpha..-hANP binding sites in bovine adrenal gland by an in vitro autoradiographic technique demonstrated that these sites were highly localized in the adrenal cortex, especially the zona glomerulosa. These results suggest that the adrenal cortex may be a target organ for direct receptor-mediated actions of ..cap alpha..-hANP.

  4. Atrial natriuretic peptide inhibits cell cycle activity of embryonic cardiac progenitor cells via its NPRA receptor signaling axis.

    PubMed

    Hotchkiss, Adam; Feridooni, Tiam; Baguma-Nibasheka, Mark; McNeil, Kathleen; Chinni, Sarita; Pasumarthi, Kishore B S

    2015-04-01

    The biological effects of atrial natriuretic peptide (ANP) are mediated by natriuretic peptide receptors (NPRs), which can either activate guanylyl cyclase (NPRA and NPRB) or inhibit adenylyl cyclase (NPRC) to modulate intracellular cGMP or cAMP, respectively. During cardiac development, ANP serves as an early maker of differentiating atrial and ventricular chamber myocardium. As development proceeds, expression of ANP persists in the atria but declines in the ventricles. Currently, it is not known whether ANP is secreted or the ANP-NPR signaling system plays any active role in the developing ventricles. Thus the primary aims of this study were to 1) examine biological activity of ANP signaling systems in embryonic ventricular myocardium, and 2) determine whether ANP signaling modulates proliferation/differentiation of undifferentiated cardiac progenitor cells (CPCs) and/or cardiomyocytes. Here, we provide evidence that ANP synthesized in embryonic day (E)11.5 ventricular myocytes is actively secreted and processed to its biologically active form. Notably, NPRA and NPRC were detected in E11.5 ventricles and exogenous ANP stimulated production of cGMP in ventricular cell cultures. Furthermore, we showed that exogenous ANP significantly decreased cell number and DNA synthesis of CPCs but not cardiomyocytes and this effect could be reversed by pretreatment with the NPRA receptor-specific inhibitor A71915. ANP treatment also led to a robust increase in nuclear p27 levels in CPCs compared with cardiomyocytes. Collectively, these data provide evidence that in the developing mammalian ventricles ANP plays a local paracrine role in regulating the balance between CPC proliferation and differentiation via NPRA/cGMP-mediated signaling pathways.

  5. Relationship between natriuresis and changes in plasma atrial natriuretic factor, renin activity and aldosterone levels in fasting obese subjects.

    PubMed

    Donckier, J E; Kolanowski, J; Berbinschi, A; Gerard, G; Ketelslegers, J M

    1990-01-01

    This study was conducted to assess whether changes in atrial natriuretic factor (ANF) secretion could account for the natriuresis of the early phase of fasting. To this end, 8 AM (supine) and 10 AM (standing) plasma ANF concentrations were determined daily and compared with plasma renin activity and aldosterone levels in 8 obese subjects submitted to a 7-day total fast. Depiste constant daily sodium intake (51 mmol), urinary sodium excretion increased from 35 +/- 7 to 109 +/- 8 mmol/day after 4 days of fast (p less than 0.001) and declined thereafter. Urinary ketone excretion progressively increased over the whole period of fasting (p less than 0.001). Interestingly, fasting induced a decrease in plasma ANF concentrations (p less than 0.05). A contrast analysis revealed no significant change in ANF during the initial natriuretic phase of fasting but a decrease at the end of fasting averaging 36% (p less than 0.05) and 18% (p less than 0.05) at 8 and 10 AM respectively. In contrast, plasma aldosterone rose during fasting (p less than 0.05), the difference being significant at the end of fasting (p less than 0.01). Plasma renin activity and cortisol did not change significantly over the fasting period. Postural and/or diurnal changes of ANF, aldosterone, renin and cortisol were preserved during fasting (p less than 0.01). Postural changes of ANF were, however, attenuated at the end of fasting (p less than 0.05). These data indicate that the fasting natriuresis cannot be explained by changes in ANF levels but that the loss of sodium may contribute to a decline of basal ANF levels, with an attenuation of their physiological postural changes, and to a stimulation of the aldosterone secretion.

  6. Atrial Natriuretic Peptide Stimulates Dopamine Tubular Transport by Organic Cation Transporters: A Novel Mechanism to Enhance Renal Sodium Excretion

    PubMed Central

    Kouyoumdzian, Nicolás M.; Rukavina Mikusic, Natalia L.; Kravetz, María C.; Lee, Brenda M.; Carranza, Andrea; Del Mauro, Julieta S.; Pandolfo, Marcela; Gironacci, Mariela M.; Gorzalczany, Susana; Toblli, Jorge E.; Fernández, Belisario E.

    2016-01-01

    The aim of this study was to demonstrate the effects of atrial natriuretic peptide (ANP) on organic cation transporters (OCTs) expression and activity, and its consequences on dopamine urinary levels, Na+, K+-ATPase activity and renal function. Male Sprague Dawley rats were infused with isotonic saline solution during 120 minutes and randomized in nine different groups: control, pargyline plus tolcapone (P+T), ANP, dopamine (DA), D-22, DA+D-22, ANP+D-22, ANP+DA and ANP+DA+D-22. Renal functional parameters were determined and urinary dopamine concentration was quantified by HPLC. Expression of OCTs and D1-receptor in membrane preparations from renal cortex tissues were determined by western blot and Na+, K+-ATPase activity was determined using in vitro enzyme assay. 3H-DA renal uptake was determined in vitro. Compared to P+T group, ANP and dopamine infusion increased diuresis, urinary sodium and dopamine excretion significantly. These effects were more pronounced in ANP+DA group and reversed by OCTs blockade by D-22, demonstrating that OCTs are implied in ANP stimulated-DA uptake and transport in renal tissues. The activity of Na+, K+-ATPase exhibited a similar fashion when it was measured in the same experimental groups. Although OCTs and D1-receptor protein expression were not modified by ANP, OCTs-dependent-dopamine tubular uptake was increased by ANP through activation of NPR-A receptor and protein kinase G as signaling pathway. This effect was reflected by an increase in urinary dopamine excretion, natriuresis, diuresis and decreased Na+, K+-ATPase activity. OCTs represent a novel target that links the activity of ANP and dopamine together in a common mechanism to enhance their natriuretic and diuretic effects. PMID:27392042

  7. Guanylyl cyclase/natriuretic peptide receptor-A signaling antagonizes phosphoinositide hydrolysis, Ca2+ release, and activation of protein kinase C

    PubMed Central

    Pandey, Kailash N.

    2014-01-01

    Thus far, three related natriuretic peptides (NPs) and three distinct sub-types of cognate NP receptors have been identified and characterized based on the specific ligand binding affinities, guanylyl cyclase activity, and generation of intracellular cGMP. Atrial and brain natriuretic peptides (ANP and BNP) specifically bind and activate guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA), and C-type natriuretic peptide (CNP) shows specificity to activate guanylyl cyclase/natriuretic peptide receptor-B (GC-B/NPRB). All three NPs bind to natriuretic peptide receptor-C (NPRC), which is also known as clearance or silent receptor. The NPRA is considered the principal biologically active receptor of NP family; however, the molecular signaling mechanisms of NP receptors are not well understood. The activation of NPRA and NPRB produces the intracellular second messenger cGMP, which serves as the major signaling molecule of all three NPs. The activation of NPRB in response to CNP also produces the intracellular cGMP; however, at lower magnitude than that of NPRA, which is activated by ANP and BNP. In addition to enhanced accumulation of intracellular cGMP in response to all three NPs, the levels of cAMP, Ca2+ and inositol triphosphate (IP3) have also been reported to be altered in different cells and tissue types. Interestingly, ANP has been found to lower the concentrations of cAMP, Ca2+, and IP3; however, NPRC has been proposed to increase the levels of these metabolic signaling molecules. The mechanistic studies of decreased and/or increased levels of cAMP, Ca2+, and IP3 in response to NPs and their receptors have not yet been clearly established. This review focuses on the signaling mechanisms of ANP/NPRA and their biological effects involving an increased level of intracellular accumulation of cGMP and a decreased level of cAMP, Ca2+, and IP3 in different cells and tissue systems. PMID:25202235

  8. Serum neutrophil gelatinase-associated lipocalin concentration reflects severity of coronary artery disease in patients without heart failure and chronic kidney disease.

    PubMed

    Katagiri, Mikako; Takahashi, Masao; Doi, Kent; Myojo, Masahiro; Kiyosue, Arihiro; Ando, Jiro; Hirata, Yasunobu; Komuro, Issei

    2016-10-01

    Serum neutrophil gelatinase-associated lipocalin (NGAL) is recognized as a useful biomarker for acute kidney injury. Recently, elevated NGAL levels were reported in patients with heart failure and cardiac events, but the association between serum NGAL and severity of coronary artery disease (CAD) has not been investigated adequately. This study aimed to evaluate the association between serum NGAL concentration and CAD severity in patients without heart failure and chronic kidney disease. Two-hundred thirteen patients [mean age: 66.2 ± 9.2 (SD)] without heart failure and chronic kidney disease (estimated glomerular filtration rate >60 mL/min/1.73 m(2)) who underwent coronary angiography were retrospectively analyzed using the SYNTAX score. The mean concentration of serum NGAL was 134.3 ± 111.3 ng/mL. A statistically significant correlation was observed between serum NGAL levels and the SYNTAX score (R = 0.18, P = 0.0091). Multivariable analysis also showed elevated serum NGAL as an independent risk factor for a high SYNTAX score (P < 0.01). Moreover, we evaluated the association of serum NGAL and brain natriuretic peptide (BNP) with the SYNTAX score. Patients with high levels of serum NGAL (>100 ng/mL) and high levels of BNP (>25 pg/mL) had a higher SYNTAX score (low-low vs. high-high: 13.8 ± 13.4 vs. 20.8 ± 18.9, P < 0.05). Serum NGAL levels were positively and significantly associated with CAD severity, and the evaluation of both serum NGAL and BNP was useful for predicting CAD in patients without renal dysfunction and heart failure. Serum NGAL might be a biomarker for CAD severity.

  9. Regulation of serum phosphate

    PubMed Central

    Lederer, Eleanor

    2014-01-01

    The regulation of serum phosphate, an acknowledged risk factor for chronic kidney disease and cardiovascular mortality, is poorly understood. The discovery of fibroblast growth factor 23 (FGF23) as a key regulator of renal phosphate handling and activation of vitamin D has revolutionized our comprehension of phosphate homeostasis. Through as yet undetermined mechanisms, circulating and dietary phosphate appear to have a direct effect on FGF23 release by bone cells that, in turn, causes renal phosphate excretion and decreases intestinal phosphate absorption through a decrease in vitamin D production. Thus, the two major phosphaturic hormones, PTH and FGF23, have opposing effects on vitamin D production, placing vitamin D at the nexus of phosphate homeostasis. While our understanding of phosphate homeostasis has advanced, the factors determining regulation of serum phosphate level remain enigmatic. Diet, time of day, season, gender, age and genetics have all been identified as significant contributors to serum phosphate level. The effects of these factors on serum phosphate have major implications for what is understood as ‘normal’ and for studies of phosphate homeostasis and metabolism. Moreover, other hormonal mediators such as dopamine, insulin-like growth factor, and angiotensin II also affect renal handling of phosphate. How the major hormone effects on phosphate handling are regulated and how the effect of these other factors are integrated to yield the measurable serum phosphate are only now beginning to be studied. PMID:24973411

  10. Preparation of A-type proanthocyanidin dimers from peanut skins and persimmon pulp and comparison of the antioxidant activity of A-type and B-type dimers.

    PubMed

    Dong, Xiao-qian; Zou, Bo; Zhang, Ying; Ge, Zhen-zhen; Du, Jing; Li, Chun-mei

    2013-12-01

    We have established a simple method for preparing large quantities of A-type dimers from peanut skin and persimmon for further structure-activity relationship study. Peanut skins were defatted with hexane and oligomeric proanthocyanidins were extracted from it with 20% of methanol, and the extract was fractionated with ethyl acetate. Persimmon tannin was extracted from persimmon with methanol acidified with 1% hydrochloric acid, after removing the sugar and small phenols, the high molecular weight persimmon tannin was partially cleaved with 6.25% hydrochloric acid in methanol. The ethyl acetate fraction from peanut skins and persimmon tannin cleaved products was chromatographed on AB-8 macroporous resin followed by Toyopearl HW-50F resin to yield about 378.3mg of A-type (epi)catechin (EC) dimer from 1 kg dry peanut skins and 34.3mg of A-type (epi)catechin-3-O-gallate (ECG) dimer and 37.7 mg of A-type (epi)gallocatechin-3-O-gallate (EGCG) dimer from 1 kg fresh persimmon fruit. The antioxidant properties of the A-type and B-type dimers were compared in five different assays, namely, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, 2,2-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical, hydroxyl radical, lipid peroxidation in mice liver homogenate and erythrocyte hemolysis in rat blood. Our results showed that both A-type and B-type dimers showed high antioxidant potency in a dose-dependent manner. In general, B-type dimers showed higher radical scavenging potency than A-type ones with the same subunits in aqueous systems. But in tissue or lipid systems, A-type dimers showed similar or even higher antioxidant potency than B-type ones.

  11. A-type and B-type lamins initiate layer assembly at distinct areas of the nuclear envelope in living cells

    SciTech Connect

    Furukawa, Kazuhiro; Ishida, Kazuya; Tsunoyama, Taka-aki; Toda, Suguru; Osoda, Shinichi; Horigome, Tsuneyoshi; Fisher, Paul A.; Sugiyama, Shin

    2009-04-15

    To investigate nuclear lamina re-assembly in vivo, Drosophila A-type and B-type lamins were artificially expressed in Drosophila lamin Dm{sub 0}null mutant brain cells. Both exogenous lamin C (A-type) and Dm{sub 0} (B-type) formed sub-layers at the nuclear periphery, and efficiently reverted the abnormal clustering of the NPC. Lamin C initially appeared where NPCs were clustered, and subsequently extended along the nuclear periphery accompanied by the recovery of the regular distribution of NPCs. In contrast, lamin Dm{sub 0} did not show association with the clustered NPCs during lamina formation and NPC spacing recovered only after completion of a closed lamin Dm{sub 0} layer. Further, when lamin Dm{sub 0} and C were both expressed, they did not co-polymerize, initiating layer formation in separate regions. Thus, A and B-type lamins reveal differing properties during lamina assembly, with A-type having the primary role in organizing NPC distribution. This previously unknown complexity in the assembly of the nuclear lamina could be the basis for intricate nuclear envelope functions.

  12. [The National Serum Bank].

    PubMed

    Magos-López, C; Sánchez-Villarreal, F; Gutiérrez, G; Tapia-Conyer, R

    1992-01-01

    A National Serum Bank was established to store sera obtained during the National Seroepidemiological Survey performed in Mexico in 1987. More than 70,000 serum samples were obtained from subjects of either sex 1-99 years of age in each of the 32 states of the country. The current collection of sera includes 28,704 male samples and 40,629 female samples. This paper describes the procedures for handling serum samples, including reception registry, storage and distribution to several laboratories for detection of measles, rubella, poliomyelitis, AIDS, diphtheria, pertussis, tetanus, brucella, salmonella, amoeba, toxoplasma, American trypanosomiasis and cysticercus. Determinations of total cholesterol were also made in order to describe its distribution and to identify the prevalence of hypercholesterolemia.

  13. Inhibition of dehydration-induced water intake by glucocorticoids is associated with activation of hypothalamic natriuretic peptide receptor-A in rat.

    PubMed

    Liu, Chao; Guan, Jing; Kang, Yunxiao; Xiu, Heming; Chen, Ying; Deng, Bao; Liu, Kunshen

    2010-12-20

    Atrial natriuretic peptide (ANP) provides a potent defense mechanism against volume overload in mammals. Its primary receptor, natriuretic peptide receptor-A (NPR-A), is localized mostly in the kidney, but also is found in hypothalamic areas involved in body fluid volume regulation. Acute glucocorticoid administration produces potent diuresis and natriuresis, possibly by acting in the renal natriuretic peptide system. However, chronic glucocorticoid administration attenuates renal water and sodium excretion. The precise mechanism underlying this paradoxical phenomenon is unclear. We assume that chronic glucocorticoid administration may activate natriuretic peptide system in hypothalamus, and cause volume depletion by inhibiting dehydration-induced water intake. Volume depletion, in turn, compromises renal water excretion. To test this postulation, we determined the effect of dexamethasone on dehydration-induced water intake and assessed the expression of NPR-A in the hypothalamus. The rats were deprived of water for 24 hours to have dehydrated status. Prior to free access to water, the water-deprived rats were pretreated with dexamethasone or vehicle. Urinary volume and water intake were monitored. We found that dexamethasone pretreatment not only produced potent diuresis, but dramatically inhibited the dehydration-induced water intake. Western blotting analysis showed the expression of NPR-A in the hypothalamus was dramatically upregulated by dexamethasone. Consequently, cyclic guanosine monophosphate (the second messenger for the ANP) content in the hypothalamus was remarkably increased. The inhibitory effect of dexamethasone on water intake presented in a time- and dose-dependent manner, which emerged at least after 18-hour dexamethasone pretreatment. This effect was glucocorticoid receptor (GR) mediated and was abolished by GR antagonist RU486. These results indicated a possible physiologic role for glucocorticoids in the hypothalamic control of water intake

  14. Diabetes-induced loss of gastric ICC accompanied by up-regulation of natriuretic peptide signaling pathways in STZ-induced diabetic mice.

    PubMed

    Wu, Yi-Song; Lu, Hong-Li; Huang, Xu; Liu, Dong-Hai; Meng, Xiang-Min; Guo, Xin; Kim, Young-chul; Xu, Wen-Xie

    2013-02-01

    Our previous study demonstrated that natriuretic peptides (NPs) play an inhibitory role in regulation of gastric smooth muscle motility. However, it is not clear whether NPs are involved in diabetics-induced loss of gastric interstitial cell of Cajal (ICC). The present study was designed to investigate the relationship between diabetics-induced loss of gastric ICC and natriuretic peptide signaling pathway in streptozotocin (STZ)-induced diabetic mice. The results showed that the protein expression levels of c-Kit and membrane-bound stem cell factor (mSCF) in gastric smooth muscle layers were decreased in STZ-induced diabetic mice. However, both mRNA and protein expression levels of natriuretic peptide receptor (NPR)-A, B and C were increased in the same place of the diabetic mice. The amplitude of spontaneous contraction in gastric antral smooth muscles was inhibited by C-type natriuretic peptide (CNP) dose-dependently and the inhibitory effect was potentiated in diabetic mice. Pretreatment of the cultured gastric smooth muscle cells (GSMCs) with different concentration of CNP can significantly decrease the mSCF expression level. 8-Bromoguanosine-3',5'-cyclomo-nophosphate (8-Br-cGMP), a membrane permeable cGMP analog, mimicked the effect of CNP but not cANF (a specific NPR-C agonist). Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay showed that high concentration of cANF (10(-6) mol/L) inhibited cell proliferation in cultured GSMCs. These findings suggest that up-regulation of NPs/NPR-A, B/cGMP and NPs/NPR-C signaling pathways may be involved in diabetes-induced loss of gastric ICC.

  15. Histone Deacetylase Inhibitors Modulate the Transcriptional Regulation of Guanylyl Cyclase/Natriuretic Peptide Receptor-A Gene

    PubMed Central

    Kumar, Prerna; Tripathi, Satyabha; Pandey, Kailash N.

    2014-01-01

    Atrial natriuretic peptide (ANP) binds guanylyl cyclase-A/natriuretic peptide receptor-A (GC-A/NPRA) and produces the intracellular second messenger, cGMP, which regulates cardiovascular homeostasis. We sought to determine the function of histone deacetylases (HDACs) in regulating Npr1 (coding for GC-A/NPRA) gene transcription, using primary mouse mesangial cells treated with class-specific HDAC inhibitors (HDACi). Trichostatin A, a pan inhibitor, and mocetinostat (MGCD0103), a class I HDAC inhibitor, significantly enhanced Npr1 promoter activity (by 8- and 10-fold, respectively), mRNA levels (4- and 5.3-fold, respectively), and NPRA protein (2.7- and 3.5-fold, respectively). However, MC1568 (class II HDAC inhibitor) had no discernible effect. Overexpression of HDAC1 and HDAC2 significantly attenuated Npr1 promoter activity, whereas HDAC3 and HDAC8 had no effect. HDACi-treated cultured cells in vitro and intact animals in vivo showed significantly reduced binding of HDAC1 and -2 and increased accumulation of acetylated H3-K9/14 and H4-K12 at the Npr1 promoter. Deletional analyses of the Npr1 promoter along with ectopic overexpression and inhibition of Sp1 confirmed that HDACi-induced Npr1 gene transcription is accomplished by Sp1 activation. Furthermore, HDACi attenuated the interaction of Sp1 with HDAC1/2 and promoted Sp1 association with p300 and p300/cAMP-binding protein-associated factor; it also promoted the recruitment of p300 and p300/cAMP-binding protein-associated factor to the Npr1 promoter. Our results demonstrate that trichostatin A and MGCD0103 enhanced Npr1 gene expression through inhibition of HDAC1/2 and increased both acetylation of histones (H3-K9/14, H4-K12) and Sp1 by p300, and their recruitment to Npr1 promoter. Our findings define a novel epigenetic regulatory mechanism that governs Npr1 gene transcription. PMID:24451378

  16. NPR-B natriuretic peptide receptors in human corneal epithelium: mRNA, immunohistochemistochemical, protein, and biochemical pharmacology studies

    PubMed Central

    Katoli, Parvaneh; Sule, Anupam; Dimitrijevich, Slobodan D.

    2010-01-01

    Purpose To demonstrate the presence of natriuretic peptide receptors (NPRs) in primary human corneal epithelial cells (p-CEPI), SV40-immortalized CEPI cells (CEPI-17-CL4) and in human corneal epithelium, and to define the pharmacology of natriuretic peptide (NP)-induced cGMP accumulation. Methods NPR presence was shown by RT–PCR, western blot analysis, and indirect immunofluoresence. cGMP accumulation was determined using an enzyme immunoassay. Results p-CEPI and CEPI-17-CL4 cells expressed mRNAs for NPR-A and NPR-B. Proteins for both NPRs were present in these cells and in human corneal epithelium. C-type NP (CNP), atrial NP (ANP) and brain NP (BNP) stimulated the accumulation of cGMP in a concentration-dependent manner in p-CEPI cells (potency; EC50s): CNP (1–53 amino acids) EC50=24±5 nM; CNP fragment (32–53 amino acids) EC50=51±8 nM; ANP (1–28 amino acids) EC50=>10 µM; BNP (32 amino acids) EC50>10 µM (all n=3–4). While the NPs were generally more potent in the CEPI-17-CL4 cells than in p-CEPI cells (n=4–9; p<0.01), the rank order of potency of the peptides was essentially the same in both cell types. Effects of CNP fragment in p-CEPI and CEPI-17-CL4 cells were potently blocked by HS-142–1, an NPR-B receptor subtype-selective antagonist (Ki=0.25±0.05 µM in CEPI-CL4–17; Ki=0.44±0.09 µM in p-CEPIs; n=6–7) but less so by an NPR-A receptor antagonist, isatin (Ki=5.3–7.8 µM, n=3–7). Conclusions Our studies showed the presence of NPR-A and NPR-B (mRNAs and protein) in p-CEPI and CEPI-17-CL4 cells and in human corneal epithelial tissue. However, detailed pharmacological studies revealed NPR-B to be the predominant functionally active receptor in both cell-types whose activation leads to the generation of cGMP. While the physiologic role(s) of the NP system in corneal function remains to be delineated, our multidisciplinary findings pave the way for such future investigations. PMID:20664698

  17. Impaired sinoatrial node function and increased susceptibility to atrial fibrillation in mice lacking natriuretic peptide receptor C

    PubMed Central

    Egom, Emmanuel E; Vella, Kimberly; Hua, Rui; Jansen, Hailey J; Moghtadaei, Motahareh; Polina, Iuliia; Bogachev, Oleg; Hurnik, Rhea; Mackasey, Martin; Rafferty, Sara; Ray, Gibanananda; Rose, Robert A

    2015-01-01

    Natriuretic peptides (NPs) are critical regulators of the cardiovascular system that are currently viewed as possible therapeutic targets for the treatment of heart disease. Recent work demonstrates potent NP effects on cardiac electrophysiology, including in the sinoatrial node (SAN) and atria. NPs elicit their effects via three NP receptors (NPR-A, NPR-B and NPR-C). Among these receptors, NPR-C is poorly understood. Accordingly, the goal of this study was to determine the effects of NPR-C ablation on cardiac structure and arrhythmogenesis. Cardiac structure and function were assessed in wild-type (NPR-C+/+) and NPR-C knockout (NPR-C−/−) mice using echocardiography, intracardiac programmed stimulation, patch clamping, high-resolution optical mapping, quantitative polymerase chain reaction and histology. These studies demonstrate that NPR-C−/− mice display SAN dysfunction, as indicated by a prolongation (30%) of corrected SAN recovery time, as well as an increased susceptibility to atrial fibrillation (6% in NPR-C+/+ vs. 47% in NPR-C−/−). There were no differences in SAN or atrial action potential morphology in NPR-C−/− mice; however, increased atrial arrhythmogenesis in NPR-C−/− mice was associated with reductions in SAN (20%) and atrial (15%) conduction velocity, as well as increases in expression and deposition of collagen in the atrial myocardium. No differences were seen in ventricular arrhythmogenesis or fibrosis in NPR-C−/− mice. This study demonstrates that loss of NPR-C results in SAN dysfunction and increased susceptibility to atrial arrhythmias in association with structural remodelling and fibrosis in the atrial myocardium. These findings indicate a critical protective role for NPR-C in the heart. Key points Natriuretic peptides (NPs) elicit their effects via multiple NP receptors (including NPR-A, NPR-B and NPR-C, with NPR-C being relatively poorly understood). We have studied the effects of NPR-C ablation on cardiac structure

  18. Canine Recombinant Adenovirus Vector Induces an Immunogenicity-Related Gene Expression Profile in Skin-Migrated CD11b+ -Type DCs

    PubMed Central

    Jouneau, Luc; Bourge, Mickael; Bouet-Cararo, Coraline; Bonneau, Michel; Zientara, Stephan; Klonjkowski, Bernard; Schwartz-Cornil, Isabelle

    2012-01-01

    Gene expression profiling of the blood cell response induced early after vaccination has previously been demonstrated to predict the immunogenicity of vaccines. In this study, we evaluated whether the analysis of the gene expression profile of skin-migrated dendritic cells (DCs) could be informative for the in vitro prediction of immunogenicity of vaccine, using canine adenovirus serotype 2 (CAV2) as vaccine vector. CAV2 has been shown to induce immunity to transgenes in several species including sheep and is an interesting alternative to human adenovirus-based vectors, based on the safety records of the parental strain in dogs and the lack of pre-existing immunity in non-host species. Skin-migrated DCs were collected from pseudo-afferent lymph in sheep. Both the CD11b+ -type and CD103+ -type skin-migrated DCs were transduced by CAV2. An analysis of the global gene response to CAV2 in the two skin DC subsets showed that the gene response in CD11b+ -type DCs was far higher and broader than in the CD103+ -type DCs. A newly released integrative analytic tool from Ingenuity systems revealed that the CAV2-modulated genes in the CD11b+ -type DCs clustered in several activated immunogenicity-related functions, such as immune response, immune cell trafficking and inflammation. Thus gene profiling in skin-migrated DC in vitro indicates that the CD11b+ DC type is more responsive to CAV2 than the CD103+ DC type, and provides valuable information to help in evaluating and possibly improving viral vector vaccine effectiveness. PMID:23300693

  19. The Human Serum Metabolome

    PubMed Central

    Psychogios, Nikolaos; Hau, David D.; Peng, Jun; Guo, An Chi; Mandal, Rupasri; Bouatra, Souhaila; Sinelnikov, Igor; Krishnamurthy, Ramanarayan; Eisner, Roman; Gautam, Bijaya; Young, Nelson; Xia, Jianguo; Knox, Craig; Dong, Edison; Huang, Paul; Hollander, Zsuzsanna; Pedersen, Theresa L.; Smith, Steven R.; Bamforth, Fiona; Greiner, Russ; McManus, Bruce; Newman, John W.; Goodfriend, Theodore; Wishart, David S.

    2011-01-01

    Continuing improvements in analytical technology along with an increased interest in performing comprehensive, quantitative metabolic profiling, is leading to increased interest pressures within the metabolomics community to develop centralized metabolite reference resources for certain clinically important biofluids, such as cerebrospinal fluid, urine and blood. As part of an ongoing effort to systematically characterize the human metabolome through the Human Metabolome Project, we have undertaken the task of characterizing the human serum metabolome. In doing so, we have combined targeted and non-targeted NMR, GC-MS and LC-MS methods with computer-aided literature mining to identify and quantify a comprehensive, if not absolutely complete, set of metabolites commonly detected and quantified (with today's technology) in the human serum metabolome. Our use of multiple metabolomics platforms and technologies allowed us to substantially enhance the level of metabolome coverage while critically assessing the relative strengths and weaknesses of these platforms or technologies. Tables containing the complete set of 4229 confirmed and highly probable human serum compounds, their concentrations, related literature references and links to their known disease associations are freely available at http://www.serummetabolome.ca. PMID:21359215

  20. [Plasma atrial natriuretic peptide level and urinary fractional sodium excretion (FENa) in patients with chronic renal failure].

    PubMed

    Czekalski, S

    1990-12-01

    The aim of the study was the search for the correlation between the degree of impairment renal function (measured by creatinine clearance) and plasma concentration of atrial natriuretic peptide (ANP) and urinary fractional sodium excretion (FENa) in patients with chronic renal diseases. Forty seven patients were studied: 10 with diminished renal reserve (group I), 10 with renal insufficiency (group II), 27 with renal failure (group III) and 10 chronically haemodialysed before dialysis (group IV). Control group consisted of 27 healthy persons. All patients and controls were on the diet containing 100-120 mmol sodium daily. Plasma ANP levels were significantly higher in all groups of patients (I--16.5 +/- 5.7; II--40.7 +/- 18.6; III--86.2 +/- 49.9; IV--196.1 +/- 51.3 pmol/l, respectively) than in controls (10.8 +/- 6.0 pmol/l). A significant correlation (r = 0.85; p less than 0.01) between plasma ANP concentration and FENa was found when the patients from all groups were pooled together. The results confirm the important role of ANP in the adaptation of reduced kidney mass to the excretion of sodium load.

  1. Pharmacological Therapy in the Heart as an Alternative to Cellular Therapy: A Place for the Brain Natriuretic Peptide?

    PubMed Central

    Rosenblatt-Velin, Nathalie; Badoux, Suzanne; Liaudet, Lucas

    2016-01-01

    The discovery that stem cells isolated from different organs have the ability to differentiate into mature beating cardiomyocytes has fostered considerable interest in developing cellular regenerative therapies to treat cardiac diseases associated with the loss of viable myocardium. Clinical studies evaluating the potential of stem cells (from heart, blood, bone marrow, skeletal muscle, and fat) to regenerate the myocardium and improve its functional status indicated that although the method appeared generally safe, its overall efficacy has remained modest. Several issues raised by these studies were notably related to the nature and number of injected cells, as well as the route and timing of their administration, to cite only a few. Besides the direct administration of cardiac precursor cells, a distinct approach to cardiac regeneration could be based upon the stimulation of the heart's natural ability to regenerate, using pharmacological approaches. Indeed, differentiation and/or proliferation of cardiac precursor cells is controlled by various endogenous mediators, such as growth factors and cytokines, which could thus be used as pharmacological agents to promote regeneration. To illustrate such approach, we present recent results showing that the exogenous administration of the natriuretic peptide BNP triggers “endogenous” cardiac regeneration, following experimental myocardial infarction. PMID:26880973

  2. C-type Natriuretic Peptide: a novel biomarker of steroid induced bone toxicity in children with acute lymphoblastic leukemia (ALL).

    PubMed

    Prickett, Timothy C R; Lyver, Amanda; Wilson, Rachel; Espiner, Eric A; Sullivan, Michael J

    2012-07-01

    Impaired bone growth and mineralization, and osteonecrosis are significant and common long-term sequelae of chemotherapy for childhood acute lymphoblastic leukemia (ALL). Here we have evaluated the relationship between linear bone growth during chemotherapy for ALL and bone derived C-type Natriuretic Peptide (CNP). CNP is known to be critical to normal endochondral bone growth in both rodents and humans, and plasma concentration of the amino terminal pro CNP (NTproCNP) is strongly correlated with concurrent height velocity in children. Plasma NTproCNP and CNP were measured by radio-immunoassay in 12 children aged 2-9 years during induction and maintenance chemotherapy for children with ALL. Height velocity was calculated from stadiometer readings at intervals of 3-12 months and related to plasma NTproCNP during each growth interval. Plasma NTproCNP was markedly suppressed in all subjects during induction chemotherapy. Brief periods of NTproCNP decline and rapid rebound during maintenance treatment coincided with the use of dexamethasone but not with other chemotherapeutics. Height velocity was markedly reduced during ALL induction but unaffected in maintenance phase, and these changes in growth were strongly correlated with plasma NTproCNP concentration. Plasma NTproCNP has potential use as a biomarker of glucocorticoid-induced bone toxicity.

  3. Modification of the diuretic and natriuretic effects of a dopamine infusion by fluid loading in preoperative cardiac surgical patients.

    PubMed

    Bryan, A G; Bolsin, S N; Vianna, P T; Haloush, H

    1995-04-01

    An intravenous infusion of dopamine at 2.5 microgram/kg/min was administered for 40 minutes to anesthetized cardiac surgical patients, and their renal function was measured. Five patients had the usual preoperative regimen of reduced fluid intake for the night and morning before surgery (nonhydrated), and five patients received normal saline, 2 mL/kg/hr intravenously, for 6 hours before anesthesia (hydrated). Renal function (measured by urine output, sodium excretion, free water clearance, and fractional excretion of sodium) was similar immediately before starting the dopamine infusion. All four variables were significantly higher in the hydrated group after 10 minutes; this difference becoming maximal after 40 minutes. Twenty minutes after stopping the dopamine infusion, renal function was similar in the two groups. This study indicates that preoperatively fluid-restricted patients demonstrate powerful salt and water conservation with reduced natriuretic and diuretic responses to a low-dose dopamine infusion when compared with hydrated patients. Patients with adequate fluid loading and intravascular volume will demonstrate a marked natriuresis and diuresis in response to low-dose dopamine infusion.

  4. Molecular pathology of natriuretic peptides in the myocardium with special regard to fatal intoxication, hypothermia, and hyperthermia.

    PubMed

    Chen, Jian-Hua; Michiue, Tomomi; Ishikawa, Takaki; Maeda, Hitoshi

    2012-09-01

    The present study investigated the molecular pathology of atrial and brain natriuretic peptides (ANP and BNP) in the myocardium to evaluate terminal cardiac function in routine forensic casework with particular regard to fatal drug intoxication (n = 18; sedative-hypnotics, n = 10; methamphetamine, n = 8), hypothermia (cold exposure, n = 13), and hyperthermia (heatstroke, n = 10), compared with that in acute ischemic heart disease (AIHD, n = 35) and congestive heart disease (CHD, n = 11) as controls (total n = 87; within 48 h postmortem). Quantitative analyses of myocardial ANP and BNP messenger RNA demonstrated that their expressions in bilateral atrial and ventricular walls were high in methamphetamine intoxication and hypothermia, comparable to those in AIHD and CHD, but were low in sedative-hypnotic intoxication and hyperthermia. In pericardial fluid, both ANP and BNP levels were increased in hypothermia, while CHD cases had an elevated BNP level, and ANP level showed a tendency to increase in hyperthermia; however, immunohistochemistry showed no evident differences in myocardial ANP and BNP among the causes of death. These findings suggest terminal high cardiac strain in methamphetamine intoxication, decreased cardiac strain in sedative-hypnotic intoxication and hyperthermia (heatstroke), and persistent congestion in hypothermia (cold exposure).

  5. Atrial natriuretic peptide down-regulates neutrophil recruitment on inflamed endothelium by reducing cell deformability and resistance to detachment force

    PubMed Central

    Morikis, Vasilios A.; Radecke, Chris; Jiang, Yanyan; Heinrich, Volkmar; Curry, Fitz-Roy; Simon, Scott I.

    2016-01-01

    BACKGROUND Recombinant atrial natriuretic peptide (ANP) is administered in patients with acute heart failure in Japan to improve renal function and hemodynamics, but its anti-inflammatory effect on activated leukocytes may also contribute to its therapeutic efficacy. OBJECTIVE Examine unconventional role of ANP in neutrophil adhesion to inflamed endothelium. METHODS Human neutrophils were perfused over endothelial monolayers in a microfluidic lab-chip assay. Cell rheology was assessed by micropipette aspiration to assess changes in cortical tension and viscosity. Fluorescence microscopy was applied to measure adhesive contact area and β2-integrin focal bond formation. RESULTS ANP inhibited neutrophil rolling and firm adhesion without influencing the upregulation of cellular adhesion molecules on endothelium or the regulation of high affinity CD18 and shedding of L-selectin during neutrophil activation. Exposed to fluid shear, integrin mediated arrest was disrupted with ANP treatment, which elicited formation of long tethers and diminished cell spreading and contact. This correlated with a ~40% increase in neutrophil viscosity and a reduction in the adhesive footprint. CONCLUSIONS A decrease in cell deformation and neutrophil flattening with ANP results in fewer integrin bond clusters, which translates to higher tensile forces and impaired adhesion strengthening and cell detachment. PMID:26639357

  6. Sustained increases in plasma C-type natriuretic peptides fail to increase concentrations in cerebrospinal fluid: Evidence from pregnant sheep.

    PubMed

    Wilson, Michele O; Barrell, Graham K; Prickett, Timothy C R; Espiner, Eric A

    2015-07-01

    C-type natriuretic peptide (CNP) is a paracrine growth factor with high abundance in CNS tissues and cerebrospinal fluid (CSF). Consistent with findings of CNP transcripts in the cerebral microvasculature and hypothalamus, CNP increases the permeability of the blood-brain barrier and reduces food intake when administered intracerebroventricularly in rodents. Whether high concentrations of CNP in plasma can affect CSF levels is unknown. Accordingly we have studied changes (days 4, 87 and 116) in concurrent plasma and CSF concentrations of CNP peptides in pregnant sheep - a physiologically unique setting in which plasma CNP is elevated for prolonged periods. Preliminary studies in non pregnant sheep showed stable CNP levels in CSF during repetitive sampling. Compared with values in non pregnant controls, plasma concentrations of CNP peptides were markedly raised (30-fold) at days 87 and 116 in pregnant sheep, yet CSF levels in the two groups did not differ. CNP peptides in CSF decreased from day 4 to day 87 in pregnant sheep, possibly reflecting an adaptive response of the cerebral vasculature to increased hemodynamic load. We conclude that sustained high concentrations of CNP - far exceeding levels encountered in human pathophysiology - fail to affect CNP peptide levels in CSF.

  7. [Effects of xinshuaikang granule on cardiac function and atrial natriuretic polypeptide levels in rabbits with experimental congestive heart failure].

    PubMed

    Jin, X C; Sun, J Z; Wang, X

    1996-07-01

    Xinshuaikang (XSK) granule mainly consisted of Radix Ginseng, Aconifum carmichaeli, Ligustici wallichii, Semen Lepidii seu Descurainiae, etc. Thirty-five white rabbits of Japanese strain with big ears were used and five groups were divided randomly. The models of chronic heart failure (CHF) was made by injection of adriamycin through the marginal vein of rabbit's ear. Only one group without adriamycin injection was taken as blank group. After the making of models, Xinbao (XB) was used to treat one group which was regarded as control group, XSK was used to treat two model groups, one used higher dose, the other one used lower dose. Fifteen days was taken as a course of treatment. The results were: the body weight of all model groups was heavier than that without adriamycin. After a course of treatment, the body weight of the groups treated by XSK or XB decreased rapidly, the general conditions of the three groups were improved; the two drugs could reduce heart rate and enhance heart function, at the same time they reduced the level of atrial natriuretic polypeptide (ANP) in plasma. The best results was obtained in XSK group with higher dose, the effect of XSK group with lower dose was equivalent to that of XB group. Hence, XSK granule could enhance the CHF rabbits' heart function, improve their heart endocrine activity, this drug had a reliable effect on CHF.

  8. Atrial natriuretic peptide degradation by CPA47 cells - Evidence for a divalent cation-independent cell-surface proteolytic activity

    NASA Technical Reports Server (NTRS)

    Frost, S. J.; Chen, Y. M.; Whitson, P. A.

    1992-01-01

    Atrial natriuretic peptide (ANP) is rapidly cleared and degraded in vivo. Nonguanylate-cyclase receptors (C-ANPR) and a metalloproteinase, neutral endopeptidase (EC 3.4.24.11) (NEP 24.11), are thought to be responsible for its metabolism. We investigated the mechanisms of ANP degradation by an endothelial-derived cell line, CPA47. CPA47 cells degraded 88 percent of 125I-ANP after 1 h at 37 degrees C as determined by HPLC. Medium preconditioned by these cells degraded 41 percent of the 125I-ANP, and this activity was inhibited by a divalent cation chelator, EDTA. Furthermore, a cell-surface proteolytic activity degraded 125I-ANP in the presence of EDTA when receptor-mediated endocytosis was inhibited either by low temperature (4 degrees C) or by hyperosmolarity at 37 degrees C. The metalloproteinase, NEP 24.11, is unlikely to be the cell-surface peptidase because 125I-ANP is degraded by CPA47 cells at 4 degrees C in the presence of 5 mM EDTA. These data indicate that CPA47 cells can degrade ANP by a novel divalent cation-independent cell-surface proteolytic activity.

  9. Brain natriuretic peptide levels in six basic underwater demolitions/SEAL recruits presenting with swimming induced pulmonary edema (SIPE).

    PubMed

    Shearer, Damon; Mahon, Richard

    2009-01-01

    Swimming induced pulmonary edema (SIPE) is associated with both SCUBA diving and strenuous surface swimming; however, the majority of reported cases and clinically observed cases tend to occur during or after aggressive surface swimming. Capillary stress failure appears to be central to the pathophysiology of this disorder. Regional pulmonary capillaries are exposed to relatively high pressures secondary to increased vascular volume, elevation of pulmonary vascular resistance, and regional differences in perfusion secondary to forces of gravity and high cardiac output. Acute pulmonary edema can be classified as either cardiogenic or noncardiogenic or both. Cardiogenic pulmonary edema occurs when the pulmonary capillary hydrostatic pressure exceeds plasma oncotic pressure. Noncardiogenic pulmonary edema occurs when pulmonary capillary permeability is increased. Given the pathophysiology noted above, SIPE can be described as a cardiogenic pulmonary edema, at least in part, since an increased transalveolar pressure gradient has been implicated in the pathogenesis of SIPE. Brain natriuretic peptide (BNP) is used in the clinical setting to differentiate cardiac from pulmonary sources of dyspnea, specifically to diagnose cardiogenic pulmonary edema. During clinical management, BNP levels were drawn on six BUD/S recruits simultaneously presenting with pulmonary complaints consistent with SIPE, after an extended surface bay swim. This paper analyzes that data after de-identification and reviews the pathophysiology and clinical management of SIPE.

  10. Sensitive radioimmunoassay of. cap alpha. human atrial natriuretic polypeptide using monoclonal antibody recognizing human form ring structure

    SciTech Connect

    Naomi, S.; Umeda, T.; Iwaoka, T.; Miura, F.; Ohno, M.; Sasaki, M.; Oishi, S.; Sato, T.; Takatsu, K.

    1988-01-01

    A monoclonal antibody (C351) against ..cap alpha.. human atrial natriuretic polypeptide (..cap alpha..hANP) recognizing human form ring structure was established and applied to a radioimmunoassay of plasma ..cap alpha..hANP. The minimum detectable amount in terms of 10 % radioligand displacement relative to zero dose were 0.28 fmol/tube, corresponding to 0.7 fmol/ml in plasma after extraction using Sep-Pak C18 cartridges. When the mean plasma levels at recumbent position in fasted morning were compared in 10 young (<30 years) and 10 elderly (greater than or equal to50 years) healthy subjects taking normal sodium diet, it was slightly higher in the latter. After i.v. infusion of hypertonic saline at a rate of 0.24 ml/kg/min for 20 min in 6 normal subjects (26 to 35 years), it was increased from 4.1 +/- 0.4 to 5.9 +/- 0.7 fmol/ml (p<0.01). In 6 patients with essential hypertension (34 to 57 years), it was elevated with high salt intake. From these results, the radioimmunoassay of plasma IR-..cap alpha..hANP using MAb C351 seems to be quite suitable to detect rather small changes at low plasma concentrations and to investigate a physiological importance of ..cap alpha..hANP in man.

  11. Beta-adrenergic modulation of the release of atrial natriuretic factor from rat cardiac atria in vitro

    SciTech Connect

    Brown, A.; Imada, T.; Takayanagi, B.; Inagami, T.

    1986-03-01

    Several stimulatory factors for the release of atrial natriuretic factor, such as atrial stretch, atrial pacing and vasopressin, have been reported. We studied the effects of the adrenergic nervous system on the release of ANF using an in vitro perfusion system. Right and left atria from Sprague-Dawley rats were quartered and perfused with Krebs-Ringer bicarbonate solution gassed with 95% CO/sub 2//5% O/sub 2/ at 37/sup 0/C. Perfusate factions were collected every 2 minutes. Fractions were collected 20 minutes before and for 2 hours during the administration of test agents. ANF was measured by radioimmunoassay. Within 10 minutes of exposure to 10/sup -6/M isoproterenol, ANF secretion fell to less than 50% of its baseline level. However, beta agonists showed a stimulatory effect of 4-5 fold. Carbachol, in a concentration of 10/sup -2/M was used to demonstrate the viability of the atria exposed to isoproterenol, and produced a stimulation of ANF release of 4-6 times the basal level. The adrenergic nervous system can modulate ANF release in vitro. Further studies are being performed with selective beta agonists and antagonists to elucidate these results.

  12. An analogue of atrial natriuretic peptide (C-ANP4-23) modulates glucose metabolism in human differentiated adipocytes.

    PubMed

    Ruiz-Ojeda, Francisco Javier; Aguilera, Concepción María; Rupérez, Azahara Iris; Gil, Ángel; Gomez-Llorente, Carolina

    2016-08-15

    The present study was undertaken to investigate the effects of C-atrial natriuretic peptide (C-ANP4-23) in human adipose-derived stem cells differentiated into adipocytes over 10 days (1 μM for 4 h). The intracellular cAMP, cGMP and protein kinase A levels were determined by ELISA and gene and protein expression were determined by qRT-PCR and Western blot, respectively, in the presence or absence of C-ANP4-23. The levels of lipolysis and glucose uptake were also determined. C-ANP4-23 treatment significantly increased the intracellular cAMP levels and the gene expression of glucose transporter type 4 (GLUT4) and protein kinase, AMP-activated, alpha 1 catalytic subunit (AMPK). Western blot showed a significant increase in GLUT4 and phosphor-AMPKα levels. Importantly, the adenylate cyclase inhibitor SQ22536 abolished these effects. Additionally, C-ANP4-23 increased glucose uptake by 2-fold. Our results show that C-ANP4-23 enhances glucose metabolism and might contribute to the development of new peptide-based therapies for metabolic diseases. PMID:27181211

  13. Receptors for atrial natriuretic peptide (ANP) and regulation of thyroglobulin secretion by ANP in human thyroid cells

    SciTech Connect

    Sellitti, D.F.; Tseng, Y.C.L.; Wartofsky, L. Walter Reed Army Medical Center, Washington, DC )

    1989-01-01

    Specific binding sites for atrial natriuretic peptide (ANP) were identified and characterized in primary cultures of human thyroid cells. Saturation analysis using ({sup 125}I) {alpha} rat (1-28) ANP as the ligand showed a single class of high affinity binding which was inhibited by atriopeptin I and the {alpha} -human form of ANP, but not by a C-terminal fragment (13-28) of the peptide. The number of ANP binding sites in these cultures was not altered by the thyroid hormone concentration of the medium. In a dose-response experiment, thyroglobulin secretion was significantly reduced in the presence of 0.01 nM ANP and was maximally reduced with 10 nM ANP. Cyclic GMP production was increased threefold in the presence of 100 nM ANP, but was unchanged with lower doses of the peptides. The finding of receptors in thyroid follicular cells suggests a hitherto unrecognized role of ANP in the thyroid gland.

  14. Volume Assessment in Mechanically Ventilated Critical Care Patients Using Bioimpedance Vectorial Analysis, Brain Natriuretic Peptide, and Central Venous Pressure

    PubMed Central

    House, Andrew A.; Haapio, Mikko; Lentini, Paolo; Bobek, Ilona; de Cal, Massimo; Cruz, Dinna N.; Virzì, Grazia M.; Carraro, Rizzieri; Gallo, Giampiero; Piccinni, Pasquale; Ronco, Claudio

    2011-01-01

    Purpose. Strategies for volume assessment of critically ill patients are limited, yet early goal-directed therapy improves outcomes. Central venous pressure (CVP), Bioimpedance Vectorial Analysis (BIVA), and brain natriuretic peptide (BNP) are potentially useful tools. We studied the utility of these measures, alone and in combination, to predict changing oxygenation. Methods. Thirty-four mechanically ventilated patients, 26 of whom had data beyond the first study day, were studied. Relationships were assessed between CVP, BIVA, BNP, and oxygenation index (O2I) in a cross-sectional (baseline) and longitudinal fashion using both univariate and multivariable modeling. Results. At baseline, CVP and O2I were positively correlated (R = 0.39; P = .021), while CVP and BIVA were weakly correlated (R = −0.38; P = .025). The association between slopes of variables over time was negligible, with the exception of BNP, whose slope was correlated with O2I (R = 0.40; P = .044). Comparing tertiles of CVP, BIVA, and BNP slopes with the slope of O2I revealed only modest agreement between BNP and O2I (kappa = 0.25; P = .067). In a regression model, only BNP was significantly associated with O2I; however, this was strengthened by including CVP in the model. Conclusions. BNP seems to be a valuable noninvasive measure of volume status in critical care and should be assessed in a prospective manner. PMID:21151535

  15. B-type nuclear lamin and the nuclear pore complex Nup107-160 influences maintenance of the spindle envelope required for cytokinesis in Drosophila male meiosis

    PubMed Central

    Hayashi, Daisuke; Tanabe, Karin; Katsube, Hiroka

    2016-01-01

    ABSTRACT In higher eukaryotes, nuclear envelope (NE) disassembly allows chromatin to condense and spindle microtubules to access kinetochores. The nuclear lamina, which strengthens the NE, is composed of a polymer meshwork made of A- and B-type lamins. We found that the B-type lamin (Lam) is not fully disassembled and continues to localize along the spindle envelope structure during Drosophila male meiosis I, while the A-type lamin (LamC) is completely dispersed throughout the cytoplasm. Among the nuclear pore complex proteins, Nup107 co-localized with Lam during this meiotic division. Surprisingly, Lam depletion resulted in a higher frequency of cytokinesis failure in male meiosis. We also observed the similar meiotic phenotype in Nup107-depleted cells. Abnormal localization of Lam was found in the Nup-depleted cells at premeiotic and meiotic stages. The central spindle microtubules became abnormal and recruitment of a contractile ring component to the cleavage sites was disrupted in Lam-depleted cells and Nup107-depleted cells. Therefore, we speculate that both proteins are required for a reinforcement of the spindle envelope, which supports the formation of central spindle microtubules essential for cytokinesis in Drosophila male meiosis. PMID:27402967

  16. B-type nuclear lamin and the nuclear pore complex Nup107-160 influences maintenance of the spindle envelope required for cytokinesis in Drosophila male meiosis.

    PubMed

    Hayashi, Daisuke; Tanabe, Karin; Katsube, Hiroka; Inoue, Yoshihiro H

    2016-08-15

    In higher eukaryotes, nuclear envelope (NE) disassembly allows chromatin to condense and spindle microtubules to access kinetochores. The nuclear lamina, which strengthens the NE, is composed of a polymer meshwork made of A- and B-type lamins. We found that the B-type lamin (Lam) is not fully disassembled and continues to localize along the spindle envelope structure during Drosophila male meiosis I, while the A-type lamin (LamC) is completely dispersed throughout the cytoplasm. Among the nuclear pore complex proteins, Nup107 co-localized with Lam during this meiotic division. Surprisingly, Lam depletion resulted in a higher frequency of cytokinesis failure in male meiosis. We also observed the similar meiotic phenotype in Nup107-depleted cells. Abnormal localization of Lam was found in the Nup-depleted cells at premeiotic and meiotic stages. The central spindle microtubules became abnormal and recruitment of a contractile ring component to the cleavage sites was disrupted in Lam-depleted cells and Nup107-depleted cells. Therefore, we speculate that both proteins are required for a reinforcement of the spindle envelope, which supports the formation of central spindle microtubules essential for cytokinesis in Drosophila male meiosis.

  17. Studies of peptide a- and b-type fragment ions using stable isotope labeling and integrated ion mobility/tandem mass spectrometry.

    PubMed

    Riba Garcia, Isabel; Giles, Kevin; Bateman, Robert H; Gaskell, Simon J

    2008-12-01

    The structures of peptide a- and b-type fragment ions were studied using synthetic peptides including a set of isomeric peptides, differing in the sequence location of an alanine residue labeled with (15)N and uniformly with (13)C. The pattern of isotope labeling of second-generation fragment ions derived via a(n) and b(n) ions (where n = 4 or 5) suggested that these intermediates existed in part as macrocyclic structures, where alternative sites of ring opening gave rise to different linear forms whose simple cleavage might give rise to the observed final products. Similar conclusions were derived from combined ion mobility/tandem MS analyses where different fragmentation patterns were observed for isomeric a- or b-type ions that display different ion mobilities. These analyses were facilitated by a new approach to the processing of ion mobility/tandem MS data, from which distinct and separate product ion spectra are derived from ions that are incompletely separated by ion mobility. Finally, an example is provided of evidence for a macrocyclic structure for b(n) ions where n = 8 or 9.

  18. Three novel B-type mannose-specific lectins of Cynoglossus semilaevis possess varied antibacterial activities against Gram-negative and Gram-positive bacteria.

    PubMed

    Sun, Yuan-yuan; Liu, Li; Li, Jun; Sun, Li

    2016-02-01

    Lectins are a group of sugar-binding proteins that are important factors of the innate immune system. In this study, we examined, in a comparative manner, the expression and function of three Bulb-type (B-type) mannose-specific lectins (named CsBML1, CsBML2, and CsBML3) from tongue sole. All three lectins possess three repeats of the conserved mannose binding motif QXDXNXVXY. Expression of CsBML1, CsBML2, and CsBML3 was most abundant in liver and upregulated by bacterial infection. Recombinant (r) CsBML1, CsBML2, and CsBML3 bound to a wide arrange of bacteria in a dose-dependent manner and with different affinities. All three lectins displayed mannose-specific and calcium-dependent agglutinating capacities but differed in agglutinating profiles. rCsBML1 and rCsBML2, but not rCsBML3, killed target bacteria in vitro and inhibited bacterial dissemination in fish tissues in vivo. These results indicate for the first time that in teleost, different members of B-type mannose-specific lectins likely play different roles in antibacterial immunity. PMID:26455466

  19. Structure of Serum Albumin

    NASA Technical Reports Server (NTRS)

    Carter, Daniel C.; Ho, Joseph X.

    1994-01-01

    Because of its availability, low cost, stability, and unusual ligand-binding properties, serum albumin has been one of the mst extensively studied and applied proteins in biochemistry. However, as a protein, albumin is far from typical, and the widespread interest in and application of albumin have not been balanced by an understanding of its molecular structure. Indeed, for more than 30 years structural information was surmised based solely on techniques such as hydrodynamics, low-angle X-ray scattering, and predictive methods.

  20. Interpreting serum risperidone concentrations.

    PubMed

    Boerth, Joel M; Caley, Charles F; Goethe, John W

    2005-02-01

    Risperidone is an atypical antipsychotic commonly used for treatment of schizophrenia and other psychotic disorders. Although therapeutic drug monitoring is not routine for any of the atypical antipsychotics, serum antipsychotic concentrations are measured routinely to assess treatment nonadherence. In humans, risperidone is metabolized by cytochrome P450 2D6 to 9-hydroxyrisperidone; together these constitute the active moiety. Dose-proportional increases in serum concentrations have not been reported for the parent drug, but have been reported for 9-hydroxyrisperidone and the active moiety (i.e., the combined concentrations of risperidone and 9-hydroxyrisperidone). We describe a 34-year-old Caucasian man of Sicilian descent with a history of schizophrenia, disorganized type. He was suspected to be noncompliant with his risperidone therapy. Initially, active moiety risperidone concentrations increased linearly with prescribed dosage increases. However, with continued increases, active moiety concentrations adjusted downward and remained 17-36% below anticipated levels. We propose a method for estimating target active moiety concentrations of risperidone based on dosage-a method that may be used to guide clinicians in assessing nonadherence to risperidone treatment.

  1. Involvement of insulin-degrading enzyme in insulin- and atrial natriuretic peptide-sensitive internalization of amyloid-β peptide in mouse brain capillary endothelial cells.

    PubMed

    Ito, Shingo; Ohtsuki, Sumio; Murata, Sho; Katsukura, Yuki; Suzuki, Hiroya; Funaki, Miho; Tachikawa, Masanori; Terasaki, Tetsuya

    2014-01-01

    Cerebral clearance of amyloid-β peptide (Aβ), which is implicated in Alzheimer's disease, involves elimination across the blood-brain barrier (BBB), and we previously showed that an insulin-sensitive process is involved in the case of Aβ1-40. The purpose of this study was to clarify the molecular mechanism of the insulin-sensitive Aβ1-40 elimination across mouse BBB. An in vivo cerebral microinjection study demonstrated that [125I]hAβ1-40 elimination from mouse brain was inhibited by human natriuretic peptide (hANP), and [125I]hANP elimination was inhibited by hAβ1-40, suggesting that hAβ1-40 and hANP share a common elimination process. Internalization of [125I]hAβ1-40 into cultured mouse brain capillary endothelial cells (TM-BBB4) was significantly inhibited by either insulin, hANP, other natriuretic peptides or insulin-degrading enzyme (IDE) inhibitors, but was not inhibited by phosphoramidon or thiorphan. Although we have reported the involvement of natriuretic peptide receptor C (Npr-C) in hANP internalization, cells stably expressing Npr-C internalized [125I]hANP but not [125I]hAβ1-40, suggesting that there is no direct interaction between Npr-C and hAβ1-40. IDE was detected in plasma membrane of TM-BBB4 cells, and internalization of [125I]hAβ1-40 by TM-BBB4 cells was reduced by IDE-targeted siRNAs. We conclude that elimination of hAβ1-40 from mouse brain across the BBB involves an insulin- and ANP-sensitive process, mediated by IDE expressed in brain capillary endothelial cells.

  2. 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

  3. Food intake and body positional change alter the circadian rhythm of atrial natriuretic peptides excretion into human urine.

    PubMed

    Vesely, D L; Giordano, A T

    1991-01-01

    The 98 amino acid (a.a.) N-terminus of the 126 a.a. atrial natriuretic factor prohormone contains two natriuretic and vasodilatory peptides consisting of a.a. 1-30 (proANF 1-30) and a.a. 31-67 (proANF 31-67). The N-terminus and C-terminus (a.a. 99-126, i.e., ANF--also a vasodilatory peptide) circulate normally in humans with a circadian peak at 04:00 h in plasma. To determine if the N-terminus and C-terminus of the ANF prohormone are present in urine and possibly have a circadian variation in urine, six healthy volunteers had urine samples hourly while awake and every 3 h during sleep for five consecutive days obtained for radioimmunoassay. The sleep-awake pattern was varied so that after 2 days of normal sleep (supine)-awake (upright) positions, these volunteers were supine from 15:00 h on the third day until 10:00 h of the fourth day. They were then upright until 19:00 h that day when they became supine again until 02:30 h, and then were upright until 10:00 h of day 5. Three radioimmunoassays that immunologically recognize (a) the whole N-terminus (i.e., amino acids 1-98), (b) the midportion of the N-terminus (amino acids 31-67), and (c) the C-terminus of the ANF prohormone were utilized. ProANF 1-98, proANF 31-67, and the ANF radioimmunoassays each detected their respective peptides in urine. A circadian peak for each of these peptides was detected at 04:00 to 05:00 h whether the person was supine or upright during the night, which were significantly (p less than 0.001) higher than their concentrations in the afternoon of the previous days. Assuming a supine position during the day caused a significant (p less than 0.01) two- to threefold increase in these peptides in the urine. Food intake also increased the concentrations of proANF 1-98, proANF 31-67, and ANF in urine (p less than 0.001). Fluid intake when abstaining from food throughout the day lowered the concentration of these peptides in the urine. It was concluded that there is a circadian rhythm in both

  4. Influence of operation factors on brittle fracture initiation and critical local normal stress in SE(B) type specimens of VVER reactor pressure vessel steels

    NASA Astrophysics Data System (ADS)

    Kuleshova, E. A.; Erak, A. D.; Kiselev, A. S.; Bubyakin, S. A.; Bandura, A. P.

    2015-12-01

    A complex of mechanical tests and fractographic studies of VVER-1000 RPV SE(B) type surveillance specimens was carried out: the brittle fracture origins were revealed (non-metallic inclusions and structural boundaries) and the correlation between fracture toughness parameters (CTOD) and fracture surface parameters (CID) was established. A computational and experimental method of the critical local normal stress determination for different origin types was developed. The values of the critical local normal stress for the structural boundary origin type both for base and weld metal after thermal exposure and neutron irradiation are lower than that for initial state due to the lower cohesive strength of grain boundaries as a result of phosphorus segregation.

  5. Defective stretch-induced release of atrial natriuretic peptide from aging hypertensive rat heart: possible role of phosphatidylinositol pathway.

    PubMed

    Brunner, F; Mouton, R; Lochner, A; Opie, L H

    1995-01-01

    Because the phosphatidylinositol pathway may be part of the signaling system associated with stretch-induced release of atrial natriuretic peptide (ANP), we tested the hypothesis that formation of the intermediate inositol-1,4,5-trisphosphate (IP3) is impaired when ANP release is decreased in response to atrial stretch in hearts from aging genetically hypertensive (GH) rats. Immunoreactive ANP release into the coronary effluent and IP3 levels were studied in cardiac tissues of isolated perfused hearts from normotensive control (WAG) or GH rats aged 4, 11, or 16 months. Left atria were repeatedly distended and released with a latex balloon. ANP was measured in coronary effluent, and IP3 was measured in cardiac tissues. In all age groups, stretch and relief of stretch evoked considerably less ANP release in spontaneously beating hearts from GH than from WAG rats. Hearts from GH rats aged 16 months released no ANP, but electrical pacing restored some stretch-induced ANP secretion. With repeated stretch and release of stretch of the left atrium for 2 min, IP3 levels increased in left atrial tissue in WAG but not in GH hearts of all age groups. IP3 levels in (unstretched) left ventricles were much lower than in left atria and were unaltered by atrial stretch. In aging GH rats, the capacity to release ANP on atrial stretch is largely lost, in association with complete suppression of stimulus-induced increase in IP3 levels. These data support a role for IP3 in stretch-mediated atrial ANP secretion and suggest a progressive uncoupling of this signaling pathway in aging hypertensive rats. PMID:7723347

  6. Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes

    PubMed Central

    Bordicchia, Marica; Liu, Dianxin; Amri, Ez-Zoubir; Ailhaud, Gerard; Dessì-Fulgheri, Paolo; Zhang, Chaoying; Takahashi, Nobuyuki; Sarzani, Riccardo; Collins, Sheila

    2012-01-01

    The ability of mammals to resist body fat accumulation is linked to their ability to expand the number and activity of “brown adipocytes” within white fat depots. Activation of β-adrenergic receptors (β-ARs) can induce a functional “brown-like” adipocyte phenotype. As cardiac natriuretic peptides (NPs) and β-AR agonists are similarly potent at stimulating lipolysis in human adipocytes, we investigated whether NPs could induce human and mouse adipocytes to acquire brown adipocyte features, including a capacity for thermogenic energy expenditure mediated by uncoupling protein 1 (UCP1). In human adipocytes, atrial NP (ANP) and ventricular NP (BNP) activated PPARγ coactivator-1α (PGC-1α) and UCP1 expression, induced mitochondriogenesis, and increased uncoupled and total respiration. At low concentrations, ANP and β-AR agonists additively enhanced expression of brown fat and mitochondrial markers in a p38 MAPK–dependent manner. Mice exposed to cold temperatures had increased levels of circulating NPs as well as higher expression of NP signaling receptor and lower expression of the NP clearance receptor (Nprc) in brown adipose tissue (BAT) and white adipose tissue (WAT). NPR-C–/– mice had markedly smaller WAT and BAT depots but higher expression of thermogenic genes such as Ucp1. Infusion of BNP into mice robustly increased Ucp1 and Pgc-1α expression in WAT and BAT, with corresponding elevation of respiration and energy expenditure. These results suggest that NPs promote “browning” of white adipocytes to increase energy expenditure, defining the heart as a central regulator of adipose tissue biology. PMID:22307324

  7. Natriuretic Peptide Receptor-C is Up-Regulated in the Intima of Advanced Carotid Artery Atherosclerosis

    PubMed Central

    Zayed, Mohamed A; Harring, Scott D; Abendschein, Dana R; Vemuri, Chandu; Lu, Dongsi; Detering, Lisa; Liu, Yongjian; Woodard, Pamela K

    2016-01-01

    Objective Natriuretic peptide receptor-C (NPR-C/NPR-3) is a cell surface protein involved in vascular remodelling that is up-regulated in atherosclerosis. NPR-C expression has not been well characterized in human carotid artery occlusive lesions. We hypothesized that NPR-C expression correlates with intimal features of vulnerable atherosclerotic carotid artery plaque. Methods To test this hypothesis, we evaluated NPR-C expression by immunohistochemistry (IHC) in carotid endarterectomy (CEA) specimens isolated from 18 patients. The grade, location, and co-localization of NPR-C in CEA specimens were evaluated using two tissue analysis techniques. Results Relative to minimally diseased CEA specimens, we observed avid NPR-C tissue staining in the intima of maximally diseased CEA specimens (65%; p=0.06). Specifically, maximally diseased CEA specimens demonstrated increased NPR-C expression in the superficial intima (61%, p=0.17), and deep intima (138% increase; p=0.05). In the superficial intima, NPR-C expression significantly co-localized with vascular smooth muscle cells (VSMCs) and macrophages. The intensity of NPR-C expression was also higher in the superficial intima plaque shoulder and cap regions, and significantly correlated with atheroma and fibroatheroma vulnerable plaque regions (β=1.04, 95% CI=0.46, 1.64). Conclusion These findings demonstrate significant NPR-C expression in the intima of advanced carotid artery plaques. Furthermore, NPR-C expression was higher in vulnerable carotid plaque intimal regions, and correlate with features of advanced disease. Our findings suggest that NPR-C may serve as a potential biomarker for carotid plaque vulnerability and progression, in patients with advanced carotid artery occlusive disease. PMID:27547837

  8. Onset and Regression of Pregnancy-Induced Cardiac Alterations in Gestationally Hypertensive Mice: The Role of the Natriuretic Peptide System.

    PubMed

    Ventura, Nicole M; Li, Terry Y; Tse, M Yat; Andrew, R David; Tayade, Chandrakant; Jin, Albert Y; Pang, Stephen C

    2015-12-01

    Pregnancy induces cardiovascular adaptations in response to increased volume overload. Aside from the hemodynamic changes that occur during pregnancy, the maternal heart also undergoes structural changes. However, cardiac modulation in pregnancies complicated by gestational hypertension is incompletely understood. The objectives of the current investigation were to determine the role of the natriuretic peptide (NP) system in pregnancy and to assess alterations in pregnancy-induced cardiac hypertrophy between gestationally hypertensive and normotensive dams. Previously we have shown that mice lacking the expression of atrial NP (ANP; ANP(-/-)) exhibit a gestational hypertensive phenotype. In the current study, female ANP(+/+) and ANP(-/-) mice were mated with ANP(+/+) males. Changes in cardiac size and weight were evaluated across pregnancy at Gestational Days 15.5 and 17.5 and Postnatal Days 7, 14, and 28. Nonpregnant mice were used as controls. Physical measurement recordings and histological analyses demonstrated peak cardiac hypertrophy occurring at 14 days postpartum in both ANP(+/+) and ANP(-/-) dams with little to no change during pregnancy. Additionally, left ventricular expression of the renin-angiotensin system (RAS) and NP system was quantified by real-time quantitative polymerase chain reaction. Up-regulation of Agt and AT(1a) genes was observed late in pregnancy, while Nppa and Nppb genes were significantly up-regulated postpartum. Our data suggest that pregnancy-induced cardiac hypertrophy may be influenced by the RAS throughout gestation and by the NP system postpartum. Further investigations are required to gain a complete understanding of the mechanistic aspects of pregnancy-induced cardiac hypertrophy.

  9. Vascular Relaxation Induced by C-Type Natriuretic Peptide Involves the Ca2+/NO-Synthase/NO Pathway

    PubMed Central

    Andrade, Fernanda A.; Restini, Carolina B. A.; Grando, Marcella D.; Ramalho, Leandra N. Z.; Bendhack, Lusiane M.

    2014-01-01

    Aims C-type natriuretic peptide (CNP) and nitric oxide (NO) are endothelium-derived factors that play important roles in the regulation of vascular tone and arterial blood pressure. We hypothesized that NO produced by the endothelial NO-synthase (NOS-3) contributes to the relaxation induced by CNP in isolated rat aorta via activation of endothelial NPR-C receptor. Therefore, the aim of this study was to investigate the putative contribution of NO through NPR-C activation in the CNP induced relaxation in isolated conductance artery. Main Methods Concentration-effect curves for CNP were constructed in aortic rings isolated from rats. Confocal microscopy was used to analyze the cytosolic calcium mobilization induced by CNP. The phosphorylation of the residue Ser1177 of NOS was analyzed by Western blot and the expression and localization of NPR-C receptors was analyzed by immunohistochemistry. Key Findings CNP was less potent in inducing relaxation in denuded endothelium aortic rings than in intact ones. L-NAME attenuated the potency of CNP and similar results were obtained in the presence of hydroxocobalamin, an intracellular NO0 scavenger. CNP did not change the phosphorylation of Ser1177, the activation site of NOS-3, when compared with control. The addition of CNP produced an increase in [Ca2+]c in endothelial cells and a decrease in [Ca2+]c in vascular smooth muscle cells. The NPR-C-receptors are expressed in endothelial and adventitial rat aortas. Significance These results suggest that CNP-induced relaxation in intact aorta isolated from rats involves NO production due to [Ca2+]c increase in endothelial cells possibly through NPR-C activation expressed in these cells. The present study provides a breakthrough in the understanding of the close relationship between the vascular actions of nitric oxide and CNP. PMID:24787693

  10. The effects of atrial natriuretic peptide and glucagon on proximal glomerulo-tubular balance in anaesthetized rats.

    PubMed

    Harris, P J; Skinner, S L; Zhuo, J

    1988-08-01

    1. The renal actions of ANP (average dose 30 ng kg-1 min-1 and glucagon (50 ng kg-1 min-1) were compared using fractional lithium reabsorption as the index of proximal reabsorption in groups of seven rats. Doses were chosen to cause similar increases in glomerular filtration rate (GFR). Time controls were included. 2. Glucagon raised GFR 32% and absolute proximal reabsorption (APR) 26% producing 81% effective proximal glomerulo-tubular balance (GTB) which was not significantly different from the 100% expected for perfect GTB. ANP raised GFR 33% and APR 10% indicating only 30% effective GTB (P less than 0.01). This was a significantly different effect from glucagon (P less than 0.005). 3. Sodium output increased 10-fold with ANP and 3-fold with glucagon. Filtration fraction increased 33% (P less than 0.04) above the pre-treatment value with ANP but was unchanged with glucagon. Plasma renin concentration was suppressed similarly by each hormone (46 and 36%, P less than 0.05, compared with pre-treatment values). 4. Despite a change in peritubular physical factors favouring reabsorption, there was almost complete attenuation of the increase expected in APR with the ANP-induced increase in GFR. In contrast, a similar change in GFR with glucagon resulted in an almost parallel increase in APR demonstrating maintenance of proximal GTB. 5. It is concluded that in the anaesthetized rat, ANP but not glucagon profoundly inhibits the increase in proximal reabsorption that normally follows an increase in filtered load. Such an action would contribute to the more potent natriuretic activity of ANP compared with glucagon.

  11. Catecholamines, cardiac natriuretic peptides and chromogranin A: evolution and physiopathology of a 'whip-brake' system of the endocrine heart.

    PubMed

    Tota, Bruno; Cerra, Maria Carmela; Gattuso, Alfonsina

    2010-09-15

    In the past 50 years, extensive evidence has shown the ability of vertebrate cardiac non-neuronal cells to synthesize and release catecholamines (CA). This formed the mindset behind the search for the intrinsic endocrine heart properties, culminating in 1981 with the discovery of the natriuretic peptides (NP). CA and NP, co-existing in the endocrine secretion granules and acting as major cardiovascular regulators in health and disease, have become of great biomedical relevance for their potent diagnostic and therapeutic use. The concept of the endocrine heart was later enriched by the identification of a growing number of cardiac hormonal substances involved in organ modulation under normal and stress-induced conditions. Recently, chromogranin A (CgA), a major constituent of the secretory granules, and its derived cardio-suppressive and antiadrenergic peptides, vasostatin-1 and catestatin, were shown as new players in this framework, functioning as cardiac counter-regulators in 'zero steady-state error' homeostasis, particularly under intense excitatory stimuli, e.g. CA-induced myocardial stress. Here, we present evidence for the hypothesis that is gaining support, particularly among human cardiologists. The actions of CA, NP and CgA, we argue, may be viewed as a hallmark of the cardiac capacity to organize 'whip-brake' connection-integration processes in spatio-temporal networks. The involvement of the nitric oxide synthase (NOS)/nitric oxide (NO) system in this configuration is discussed. The use of fish and amphibian paradigms will illustrate the ways that incipient endocrine-humoral agents have evolved as components of cardiac molecular loops and important intermediates during evolutionary transitions, or in a distinct phylogenetic lineage, or under stress challenges. This may help to grasp the old evolutionary roots of these intracardiac endocrine/paracrine networks and how they have evolved from relatively less complicated designs. The latter can also be used

  12. Hypergravity differentially modulates cGMP efflux in human melanocytic cells stimulated by nitric oxide and natriuretic peptides

    NASA Astrophysics Data System (ADS)

    Ivanova, K.; Stieber, C.; Lambers, B.; Block, I.; Krieg, R.; Wellmann, A.; Gerzer, R.

    Nitric oxide NO plays a key role in many patho physiologic processes including inflammation and skin cancer The diverse cellular effects of NO are mainly mediated by activation of the soluble guanylyl cyclase sGC isoform that leads to increases in intracellular cGMP levels whereas the membrane-bound isoforms serve as receptors for natriuretic peptides e g ANP In human skin epidermal melanocytes represent the principal cells for skin pigmentation by synthesizing the pigment melanin Melanin acts as a scavenger for free radicals that may arise during metabolic stress as a result of potentially harmful effects of the environment In previous studies we found that long-term exposure to hypergravity stimulated cGMP efflux in normal human melanocytes NHMs and non-metastatic melanoma cells at least partly by an enhanced expression of the multidrug resistance proteins MRP and cGMP transporters MRP4 5 The present study investigated whether hypergravity generated by centrifugal acceleration may modulate the cGMP efflux in NO-stimulated NHMs and melanoma cells MCs with different metastatic potential The NONOates PAPA-NO and DETA-NO were used as direct NO donors for cell stimulation In the presence of 0 1 mM DETA-NO t 1 2 sim 20 h long-term application of hypergravity up to 5 g for 24 h reduced intracellular cGMP levels by stimulating cGMP efflux in NHMs and non-metastatic MCs in comparison to 1 g whereas exposure to 5 g for 6 h in the presence of 0 1 mM PAPA-NO t 1 2 sim 30 min was not effective The hypergravity-stimulated

  13. Natriuretic Peptides as Cardiovascular Safety Biomarkers in Rats: Comparison With Blood Pressure, Heart Rate, and Heart Weight.

    PubMed

    Engle, Steven K; Watson, David E

    2016-02-01

    Cardiovascular (CV) toxicity is an important cause of failure during drug development. Blood-based biomarkers can be used to detect CV toxicity during preclinical development and prioritize compounds at lower risk of causing such toxicities. Evidence of myocardial degeneration can be detected by measuring concentrations of biomarkers such as cardiac troponin I and creatine kinase in blood; however, detection of functional changes in the CV system, such as blood pressure, generally requires studies in animals with surgically implanted pressure transducers. This is a significant limitation because sustained changes in blood pressure are often accompanied by changes in heart rate and together can lead to cardiac hypertrophy and myocardial degeneration in animals, and major adverse cardiovascular events (MACE) in humans. Increased concentrations of NPs in blood correlate with higher risk of cardiac mortality, all-cause mortality, and MACE in humans. Their utility as biomarkers of CV function and toxicity in rodents was investigated by exploring the relationships between plasma concentrations of NTproANP and NTproBNP, blood pressure, heart rate, and heart weight in Sprague Dawley rats administered compounds that caused hypotension or hypertension, including nifedipine, fluprostenol, minoxidil, L-NAME, L-thyroxine, or sunitinib for 1-2 weeks. Changes in NTproANP and/or NTproBNP concentrations were inversely correlated with changes in blood pressure. NTproANP and NTproBNP concentrations were inconsistently correlated with relative heart weights. In addition, increased heart rate was associated with increased heart weights. These studies support the use of natriuretic peptides and heart rate to detect changes in blood pressure and cardiac hypertrophy in short-duration rat studies. PMID:26609138

  14. Guanylyl cyclase/natriuretic peptide receptor-A gene disruption causes increased adrenal angiotensin II and aldosterone levels.

    PubMed

    Zhao, Di; Vellaichamy, Elangovan; Somanna, Naveen K; Pandey, Kailash N

    2007-07-01

    Disruption of the guanylyl cyclase-A/natriuretic peptide receptor-A (GC-A/NPRA) gene leads to elevated arterial blood pressure and congestive heart failure in mice lacking NPRA. This study was aimed at determining whether Npr1 (coding for GC-A/NPRA) gene copy number affects adrenal ANG II and aldosterone (Aldo) levels in a gene-dose-dependent manner in Npr1 gene-targeted mice. Adrenal ANG II and Aldo levels increased in 1-copy mice compared with 2-copy mice, but decreased in 3-copy and 4-copy mice. In contrast, renal ANG II levels decreased in 1-copy (25%), 3-copy (38%), and 4-copy (39%) mice compared with 2-copy mice. The low-salt diet stimulated adrenal ANG II and Aldo levels in 1-copy (20 and 2,441%), 2-copy (15 and 2,339%), 3-copy (20 and 424%), and 4-copy (31 and 486%) mice, respectively. The high-salt diet suppressed adrenal ANG II and Aldo levels in 1-copy (46 and 29%) and 2-copy (38 and 17%) mice. On the other hand, the low-salt diet stimulated renal ANG II levels in 1-copy (45%), 2-copy (45%), 3-copy (59%), and 4-copy (48%) mice. However, the high-salt diet suppressed renal ANG II levels in 1-copy (28%) and 2-copy (27%) mice. In conclusion, NPRA signaling antagonizes adrenal ANG II and Aldo levels in a gene-dose dependent manner. Increased adrenal ANG II and Aldo levels may play an important role in elevated arterial blood pressure and progressive hypertension, leading to renal and vascular injury in Npr1 gene-disrupted mice.

  15. 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

  16. Renal Overexpression of Atrial Natriuretic Peptide and Hypoxia Inducible Factor-1α as Adaptive Response to a High Salt Diet

    PubMed Central

    Della Penna, Silvana Lorena; Cao, Gabriel; Carranza, Andrea; Zotta, Elsa; Gorzalczany, Susana; Cerrudo, Carolina Susana; Rukavina Mikusic, Natalia Lucía; Correa, Alicia; Trida, Verónica; Toblli, Jorge Eduardo; Fernández, Belisario Enrique

    2014-01-01

    In the kidney, a high salt intake favors oxidative stress and hypoxia and causes the development of fibrosis. Both atrial natriuretic peptide (ANP) and hypoxia inducible factor (HIF-1α) exert cytoprotective effects. We tested the hypothesis that renal expression of ANP and HIF-1α is involved in a mechanism responding to the oxidative stress produced in the kidneys of rats chronically fed a high sodium diet. Sprague-Dawley rats were fed with a normal salt (0.4% NaCl) (NS) or a high salt (8% NaCl) (HS) diet for 3 weeks, with or without the administration of tempol (T), an inhibitor of oxidative stress, in the drinking water. We measured the mean arterial pressure (MAP), glomerular filtration rate (GFR), and urinary sodium excretion (UVNa). We evaluated the expression of ANP, HIF-1α, and transforming growth factor (TGF-β1) in renal tissues by western blot and immunohistochemistry. The animals fed a high salt diet showed increased MAP and UVNa levels and enhanced renal immunostaining of ANP, HIF-1α, and TGF-β1. The administration of tempol together with the sodium overload increased the natriuresis further and prevented the elevation of blood pressure and the increased expression of ANP, TGF-β1, and HIF-1α compared to their control. These findings suggest that HIF-1α and ANP, synthesized by the kidney, are involved in an adaptive mechanism in response to a sodium overload to prevent or attenuate the deleterious effects of the oxidative stress and the hypoxia on the development of fibrosis. PMID:24689065

  17. 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

  18. Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism.

    PubMed

    Lankeit, Mareike; Jiménez, David; Kostrubiec, Maciej; Dellas, Claudia; Kuhnert, Katherina; Hasenfuß, Gerd; Pruszczyk, Piotr; Konstantinides, Stavros

    2014-06-01

    The optimal N-terminal pro-brain natriuretic peptide (NT-proBNP) cut-off value for risk stratification of pulmonary embolism remains controversial. In this study we validated and compared different proposed NT-proBNP cut-off values in 688 normotensive patients with pulmonary embolism. During the first 30 days, 28 (4.1%) patients reached the primary outcome (pulmonary embolism-related death or complications) and 29 (4.2%) patients died. Receiver operating characteristic analysis yielded an area under the curve of 0.70 (0.60-0.80) for NT-proBNP. A cut-off value of 600 pg·mL(-1) was associated with the best prognostic performance (sensitivity 86% and specificity 50%) and the highest odds ratio (6.04 (95% CI 2.07-17.59), p=0.001) compared to the cut-off values of 1000, 500 or 300 pg·mL(-1). Using multivariable logistic regression analysis, NT-proBNP ≥ 600 pg·mL(-1) had a prognostic impact on top of that of the simplified Pulmonary Embolism Severity Index and right ventricular dysfunction on echocardiography (OR 4.27 (95% CI 1.22-15.01); p=0.024, c-index 0.741). The use of a stepwise approach based on the simplified Pulmonary Embolism Severity Index, NT-proBNP ≥ 600 pg·mL(-1) and echocardiography helped optimise risk assessment. Our findings confirm the prognostic value of NT-proBNP and suggest that a cut-off value of 600 pg·mL(-1) is most appropriate for risk stratification of normotensive patients with pulmonary embolism. NT-proBNP should be used in combination with a clinical score and an imaging procedure for detecting right ventricular dysfunction.

  19. During Cytochrome c Maturation CcmI Chaperones the Class I Apocytochromes until the Formation of Their b-Type Cytochrome Intermediates.

    PubMed

    Verissimo, Andreia F; Shroff, Namita P; Daldal, Fevzi

    2015-07-01

    The c-type cytochromes are electron transfer proteins involved in energy transduction. They have heme-binding (CXXCH) sites that covalently ligate heme b via thioether bonds and are classified into different classes based on their protein folds and the locations and properties of their cofactors. Rhodobacter capsulatus produces various c-type cytochromes using the cytochrome c maturation (Ccm) System I, formed from the CcmABCDEFGHI proteins. CcmI, a component of the heme ligation complex CcmFHI, interacts with the heme-handling protein CcmE and chaperones apocytochrome c2 by binding its C-terminal helix. Whether CcmI also chaperones other c-type apocytochromes, and the effects of heme on these interactions were unknown previously. Here, we purified different classes of soluble and membrane-bound c-type apocytochromes (class I, c2 and c1, and class II c') and investigated their interactions with CcmI and apoCcmE. We report that, in the absence of heme, CcmI and apoCcmE recognized different classes of c-type apocytochromes with different affinities (nM to μM KD values). When present, heme induced conformational changes in class I apocytochromes (e.g. c2) and decreased significantly their high affinity for CcmI. Knowing that CcmI does not interact with mature cytochrome c2 and that heme converts apocytochrome c2 into its b-type derivative, these findings indicate that CcmI holds the class I apocytochromes (e.g. c2) tightly until their noncovalent heme-containing b-type cytochrome-like intermediates are formed. We propose that these intermediates are subsequently converted into mature cytochromes following the covalent ligation of heme via the remaining components of the Ccm complex.

  20. Present-day cosmic abundances. A comprehensive study of nearby early B-type stars and implications for stellar and Galactic evolution and interstellar dust models

    NASA Astrophysics Data System (ADS)

    Nieva, M.-F.; Przybilla, N.

    2012-03-01

    Context. Early B-type stars are ideal indicators for present-day cosmic abundances since they preserve their pristine abundances and typically do not migrate far beyond their birth environments over their short lifetimes, in contrast to older stars like the Sun. They are also unaffected by depletion onto dust grains, unlike the cold/warm interstellar medium (ISM) or H ii regions. Aims: A carefully selected sample of early B-type stars in OB associations and the field within the solar neighbourhood is studied comprehensively. Quantitative spectroscopy is used to characterise their atmospheric properties in a self-consistent way. Present-day abundances for the astrophysically most interesting chemical elements are derived in order to investigate whether a present-day cosmic abundance standard can be established. Methods: High-resolution and high-S/N FOCES, FEROS and ELODIE spectra of well-studied sharp-lined early B-type stars are analysed in non-LTE. Line-profile fits based on extensive model grids and an iterative analysis methodology are used to constrain stellar parameters and elemental abundances at high accuracy and precision. Atmospheric parameters are derived from the simultaneous establishment of independent indicators, from multiple ionization equilibria and the Stark-broadened hydrogen Balmer lines, and they are confirmed by reproduction of the stars' global spectral energy distributions. Results: Effective temperatures are constrained to 1-2% and surface gravities to less than 15% uncertainty, along with accurate rotational, micro- and macroturbulence velocities. Good agreement of the resulting spectroscopic parallaxes with those from the new reduction of the Hipparcos catalogue is obtained. Absolute values for abundances of He, C, N, O, Ne, Mg, Si and Fe are determined to better than 25% uncertainty. The synthetic spectra match the observations reliably over almost the entire visual spectral range. Three sample stars, γ Ori, o Per and θ1 Ori D, are

  1. Molecular classification of an elasmobranch angiotensin receptor: quantification of angiotensin receptor and natriuretic peptide receptor mRNAs in saltwater and freshwater populations of the Atlantic stingray.

    PubMed

    Evans, Andrew N; Henning, Toni; Gelsleichter, James; Nunez, B Scott

    2010-12-01

    Among the most conserved osmoregulatory hormone systems in vertebrates are the renin-angiotensin system (RAS) and the natriuretic peptides (NPs). We examined the RAS and NP system in the euryhaline Atlantic stingray, Dasyatis sabina (Lesueur). To determine the relative sensitivity of target organs to these hormonal systems, we isolated cDNA sequences encoding the D. sabina angiotensin receptor (AT) and natriuretic peptide type-B receptor (NPR-B). We then determined the tissue-specific expression of their mRNAs in saltwater D. sabina from local Texas waters and an isolated freshwater population in Lake Monroe, Florida. AT mRNA was most abundant in interrenal tissue from both populations. NPR-B mRNA was most abundant in rectal gland tissue from both populations, and also highly abundant in the kidney of saltwater D. sabina. This study is the first to report the sequence of an elasmobranch angiotensin receptor, and phylogenetic analysis indicates that the D. sabina receptor is more similar to AT(1) vs. AT(2) proteins. This classification is further supported by molecular analysis of AT(1) and AT(2) proteins demonstrating conservation of AT(1)-specific amino acid residues and motifs in D. sabina AT. Molecular classification of the elasmobranch angiotensin receptor as an AT(1)-like protein provides fundamental insight into the evolution of the vertebrate RAS. PMID:20869458

  2. Molecular classification of an elasmobranch angiotensin receptor: quantification of angiotensin receptor and natriuretic peptide receptor mRNAs in saltwater and freshwater populations of the Atlantic stingray.

    PubMed

    Evans, Andrew N; Henning, Toni; Gelsleichter, James; Nunez, B Scott

    2010-12-01

    Among the most conserved osmoregulatory hormone systems in vertebrates are the renin-angiotensin system (RAS) and the natriuretic peptides (NPs). We examined the RAS and NP system in the euryhaline Atlantic stingray, Dasyatis sabina (Lesueur). To determine the relative sensitivity of target organs to these hormonal systems, we isolated cDNA sequences encoding the D. sabina angiotensin receptor (AT) and natriuretic peptide type-B receptor (NPR-B). We then determined the tissue-specific expression of their mRNAs in saltwater D. sabina from local Texas waters and an isolated freshwater population in Lake Monroe, Florida. AT mRNA was most abundant in interrenal tissue from both populations. NPR-B mRNA was most abundant in rectal gland tissue from both populations, and also highly abundant in the kidney of saltwater D. sabina. This study is the first to report the sequence of an elasmobranch angiotensin receptor, and phylogenetic analysis indicates that the D. sabina receptor is more similar to AT(1) vs. AT(2) proteins. This classification is further supported by molecular analysis of AT(1) and AT(2) proteins demonstrating conservation of AT(1)-specific amino acid residues and motifs in D. sabina AT. Molecular classification of the elasmobranch angiotensin receptor as an AT(1)-like protein provides fundamental insight into the evolution of the vertebrate RAS.

  3. Effect of short-term endurance training on exercise capacity, haemodynamics and atrial natriuretic peptide secretion in heart transplant recipients.

    PubMed

    Geny, B; Saini, J; Mettauer, B; Lampert, E; Piquard, F; Follenius, M; Epailly, E; Schnedecker, B; Eisenmann, B; Haberey, P; Lonsdorfer, J

    1996-01-01

    Exercise tolerance of heart transplant patients is often limited. Central and peripheral factors have been proposed to explain such exercise limitation but, to date, the leading factors remain to be determined. We examined how a short-term endurance exercise training programme may improve exercise capacity after heart transplantation, and whether atrial natriuretic peptide (ANP) release may contribute to the beneficial effects of exercise training by minimizing ischaemia and/or cardiac and circulatory congestion through its vasodilatation and haemoconcentration properties. Seven heart transplant recipients performed a square-wave endurance exercise test before and after 6 weeks of supervised training, while monitoring haemodynamic parameters, ANP and catecholamine concentrations. After training, the maximal tolerated power and the total mechanical work load increased from 130.4 (SEM 6.5) to 150.0 (SEM 6.0) W (P < 0.05) and from 2.05 (SEM 0.1) to 3.58 (SEM 0.14) kJ.kg-1 (P < 0.001). Resting heart rate decreased from 100.0 (SEM 3.4) to 92.4 (SEM 3.5) beats.min-1 (P < 0.05) but resting and exercise induced increases in cardiac output, stroke volume, right atrial, pulmonary capillary wedge, systemic and pulmonary artery pressures were not significantly changed by training. Exercise-induced decrease of systemic vascular resistance was similar before and after training. After training arterio-venous differences in oxygen content were similar but maximal lactate concentrations decreased from 6.20 (SEM 0.55) to 4.88 (SEM 0.6) mmol.l-1 (P < 0.05) during exercise. Similarly, maximal exercise noradrenaline concentration tended to decrease from 2060 (SEM 327) to 1168 (SEM 227) pg.ml-1. A significant correlation was observed between lactate and catecholamines concentrations. The ANP concentration at rest and the exercise-induced ANP concentration did not change throughout the experiment [104.8 (SEM 13.1) pg.ml-1 vs 116.0 (SEM 13.5) pg.ml-1 and 200.0 (SEM 23.0) pg.ml-1 vs 206

  4. All-Trans Retinoic Acid and Sodium Butyrate Enhance Natriuretic Peptide Receptor A Gene Transcription: Role of Histone Modification

    PubMed Central

    Kumar, Prerna; Periyasamy, Ramu; Das, Subhankar; Neerukonda, Smitha; Mani, Indra

    2014-01-01

    The objective of the present study was to delineate the mechanisms of GC-A/natriuretic peptide receptor-A (GC-A/NPRA) gene (Npr1) expression in vivo. We used all-trans retinoic acid (ATRA) and histone deacetylase (HDAC) inhibitor, sodium butyrate (NaBu) to examine the expression and function of Npr1 using gene-disrupted heterozygous (1-copy; +/−), wild-type (2-copy; +/+), and gene-duplicated heterozygous (3-copy; ++/+) mice. Npr1+/− mice exhibited increased renal HDAC and reduced histone acetyltransferase (HAT) activity; on the contrary, Npr1++/+ mice showed decreased HDAC and enhanced HAT activity compared with Npr1+/+ mice. ATRA and NaBu promoted global acetylation of histones H3-K9/14 and H4-K12, reduced methylation of H3-K9 and H3-K27, and enriched accumulation of active chromatin marks at the Npr1 promoter. A combination of ATRA-NaBu promoted recruitment of activator-complex containing E26 transformation–specific 1, retinoic acid receptor α, and HATs (p300 and p300/cAMP response element–binding protein-binding protein–associated factor) at the Npr1 promoter, and significantly increased renal NPRA expression, GC activity, and cGMP levels. Untreated 1-copy mice showed significantly increased systolic blood pressure and renal expression of α-smooth muscle actin (α-SMA) and proliferating cell nuclear antigen (PCNA) compared with 2- and 3-copy mice. Treatment with ATRA and NaBu synergistically attenuated the expression of α-SMA and PCNA and reduced systolic blood pressure in Npr1+/− mice. Our findings demonstrate that epigenetic upregulation of Npr1 gene transcription by ATRA and NaBu leads to attenuation of renal fibrotic markers and systolic blood pressure in mice with reduced Npr1 gene copy number, which will have important implications in prevention and treatment of hypertension-related renal pathophysiological conditions. PMID:24714214

  5. Brain natriuretic peptide predicts forced vital capacity of the lungs, oxygen pulse and peak oxygen consumption in physiological condition.

    PubMed

    Popovic, Dejana; Ostojic, Miodrag C; Popovic, Bojana; Petrovic, Milan; Vujisic-Tesic, Bosiljka; Kocijancic, Aleksandar; Banovic, Marko; Arandjelovic, Aleksandra; Stojiljkovic, Stanimir; Markovic, Vidan; Damjanovic, Svetozar S

    2013-05-01

    Brain natriuretic peptide (NT-pro-BNP) is used as marker of cardiac and pulmonary diseases. However, the predictive value of circulating NT-pro-BNP for cardiac and pulmonary performance is unclear in physiological conditions. Standard echocardiography, tissue Doppler and forced spirometry at rest were used to assess cardiac parameters and forced vital capacity (FVC) in two groups of athletes (16 elite male wrestlers (W), 21 water polo player (WP)), as different stress adaptation models, and 20 sedentary subjects (C) matched for age. Cardiopulmonary test on treadmill (CPET), as acute stress model, was used to measure peak oxygen consumption (peak VO2), maximal heart rate (HRmax) and peak oxygen pulse (peak VO2/HR). NT-pro-BNP was measured by immunoassey sandwich technique 10min before the test - at rest, at the beginning of the test, at maximal effort, at third minute of recovery. FVC was higher in athletes and the highest in W (WP 5.60±0.29 l; W 6.57±1.00 l; C 5.41±0.29 l; p<0.01). Peak VO2 and peak VO2/HR were higher in athletes and the highest in WP. HRmax was not different among groups. In all groups, NT-pro-BNP decreased from rest to the beginning phase, increased in maximal effort and stayed unchanged in recovery. NT-pro-BNP was higher in C than W in all phases; WP had similar values as W and C. On multiple regression analysis, in all three groups together, ΔNT-pro-BNP from rest to the beginning phase independently predicted both peak VO2 and peak VO2/HR (r=0.38, 0.35; B=37.40, 0.19; p=0.007, 0.000, respectively). NT-pro-BNP at rest predicted HRmax (r=-0.32, B=-0.22, p=0.02). Maximal NT-pro-BNP predicted FVC (r=-0.22, B=-0.07, p=0.02). These results show noticeable predictive value of NT-pro-BNP for both cardiac and pulmonary performance in physiological conditions suggesting that NT-pro-BNP could be a common regulatory factor coordinating adaptation of heart and lungs to stress condition.

  6. Expression of natriuretic peptides, nitric oxide synthase, and guanylate cyclase activity in frog mesonephros during the annual cycle.

    PubMed

    Fenoglio, Carla; Visai, Livia; Addario, Concetta; Gerzeli, Giuseppe; Milanesi, Gloria; Vaccarone, Rita; Barni, Sergio

    2004-06-01

    Natriuretic peptides (NPs), a family of structurally related hormones and nitric oxide (NO), generated by nitric oxide synthase (NOS), are believed to be involved in the regulation of fluid balance and sodium homeostasis. Differential expression and regulation of these factors depend on both physiological and pathological conditions. Both NPs and NO act in target organs through the activation of guanylate cyclase (GC) and the generation of guanosine 3',5'-cyclic monophosphate (cGMP), which is considered a common messenger for the action of these factors. The present study was designed to investigate--by histochemical methods--the expression of some NPs (proANP and ANP) and isoforms of NOS (neuronal NOS, nNOS, and inducible NOS, iNOS) in the mesonephros of Rana esculenta in different periods of the year including hibernation, to evaluate possible seasonal changes in their expression. We also studied the enzyme activity of NOS-related nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) and of GC. The experiments were performed on pieces of kidney of R. esculenta collected in their natural environment during active and hibernating life. The study was carried out using immunohistochemical techniques to demonstrate proANP, ANP, and some NOS isoforms. Antigen capture by enzyme linked immunosorbent assay (ELISA) was also performed to determine the presence of NPs in the frog kidney extract. Enzyme histochemistry was used to demonstrate the NOS-related NADPHd activity at light microscopy; GC activity was visualized at the electron microscope, using cerium as capture agent. The application of the immunohistochemical techniques demonstrated that frog mesonephros tubules express different patterns of distribution and/or expression of ANP and NOS during the annual cycle. Comparing the results obtained on active and hibernating frogs has provided interesting data; the NOS/NADPHd and GC activities showed some variations as well. Furthermore, the presence of NPs in

  7. The interaction of cadmium with atrial natriuretic factor: A study in in vivo and in vitro models

    SciTech Connect

    Giridhar, J.

    1990-01-01

    The involvement of atrial natriuretic factor (ANF) and its receptor in cadmium(Cd)-induced cardiovascular alterations and neurotoxicity is not known. This study examines the mechanisms underlying Cd-induced changes in the ANF peptide and its receptor in cardiovascular toxicity. In rats on short term Cd exposure (0.01, 0.1, 0.5 and 1.0 mg/kg, i.p., twice a day for 7 days and a maintenance period of 30 days), atrial ANF levels decreased significantly in the Cd 1 mg/kg group; plasma ANF levels were unchanged. Hypothalamic ANF content decreased significantly in 0.1-1.0 mg/kg Cd groups. Plasma renin activity and concentration were unchanged by Cd treatment. However, plasma aldosterone was significantly decreased in Cd 1.0 mg/kg group. Binding of [sup 125]I-ANF to its receptors in kidney, adrenals and aorta was not significantly altered. Cd treatment decreased urine volume indicating nephrotoxicity. Neuromodulation by ANF involved significant decrease in K[sup +] stimulated [[sup 3]H]NE release in rat hypothalamic slices. This action is proposed to be mediated by ANF-B receptors. 8Br-cGMP mimicked this action. In Cd treated animals (0.5 mg/kg twice a day for 7 days and maintained for 30 days), ANF neuromodulation in the hypothalmus was blocked, even though Cd content was undetectable. Cd preincubated (0.5 mM) slices showed a 49.1% block in neurotransmitter release indicating that Cd may block calcium channels leading to decreased K[sup +]-stimulated release of [[sup 3]H]NE. Hence, Cd-induced cardiovascular toxicity and neurotoxicity may be partly mediated by alteration in the release and possibly the synthesis of ANF peptide, disruption of ANF function through alterations in receptor dynamics and possibly alteration in cellular calcium homeostasis and membrane integrity. Central ANF function is sensitive to Cd and this effect may be partly resposible for the cardiovascular and neurotoxic responses to CD.

  8. Inefficient constitutive inhibition of P2X3 receptors by brain natriuretic peptide system contributes to sensitization of trigeminal sensory neurons in a genetic mouse model of familial hemiplegic migraine

    PubMed Central

    Marchenkova, Anna; Vilotti, Sandra; Ntamati, Niels; van den Maagdenberg, Arn MJM

    2016-01-01

    Background On trigeminal ganglion neurons, pain-sensing P2X3 receptors are constitutively inhibited by brain natriuretic peptide via its natriuretic peptide receptor-A. This inhibition is associated with increased P2X3 serine phosphorylation and receptor redistribution to non-lipid raft membrane compartments. The natriuretic peptide receptor-A antagonist anantin reverses these effects. We studied whether P2X3 inhibition is dysfunctional in a genetic familial hemiplegic migraine type-1 model produced by introduction of the human pathogenic R192Q missense mutation into the mouse CACNA1A gene (knock-in phenotype). This model faithfully replicates several properties of familial hemiplegic migraine type-1, with gain-of-function of CaV2.1 Ca2+ channels, raised levels of the algogenic peptide calcitonin gene-related peptide, and enhanced activity of P2X3 receptors in trigeminal ganglia. Results In knock-in neurons, anantin did not affect P2X3 receptor activity, membrane distribution, or serine phosphorylation level, implying ineffective inhibition by the constitutive brain natriuretic peptide/natriuretic peptide receptor-A pathway. However, expression and functional properties of this pathway remained intact together with its ability to downregulate TRPV1 channels. Reversing the familial hemiplegic migraine type-1 phenotype with the CaV2.1-specific antagonist, ω-agatoxin IVA restored P2X3 activity to wild-type level and enabled the potentiating effects of anantin again. After blocking calcitonin gene-related peptide receptors, P2X3 receptors exhibited wild-type properties and were again potentiated by anantin. Conclusions P2X3 receptors on mouse trigeminal ganglion neurons are subjected to contrasting modulation by inhibitory brain natriuretic peptide and facilitatory calcitonin gene-related peptide that both operate via complex intracellular signaling. In the familial hemiplegic migraine type-1 migraine model, the action of calcitonin gene-related peptide appears to

  9. Corynebacterium glutamicum CsoR acts as a transcriptional repressor of two copper/zinc-inducible P(1B)-type ATPase operons.

    PubMed

    Teramoto, Haruhiko; Inui, Masayuki; Yukawa, Hideaki

    2012-01-01

    The mechanism of regulation of the expression of copA and copB, encoding putative copper-translocating P(1B)-type ATPases in Corynebacterium glutamicum, was investigated. The levels of copA and copB mRNAs were upregulated in response to excess copper as well as excess zinc. Disruption of csoR, encoding a transcriptional regulator, resulted in constitutive expression of copA and copB. The CsoR protein bound to the promoter regions of the copA-csoR and the cgR_0124-copB-cgR_0126 operon. In vitro DNA binding activity was strongly inhibited by copper, but much less inhibited by zinc. A csoR-deficient mutant showed slightly increased resistance to copper, but slightly decreased resistance to zinc. These findings indicate that CsoR acts as a transcriptional repressor not only of the cognate copA-csoR operon but also of the cgR_0124-copB-cgR_0126 operon, which is not physically linked to csoR on the chromosome, and that CsoR plays a major role in copper homeostasis. PMID:23090582

  10. Different B-type methionine sulfoxide reductases in Chlamydomonas may protect the alga against high-light, sulfur-depletion, or oxidative stress.

    PubMed

    Zhao, Lei; Chen, Mei; Cheng, Dongmei; Yang, Haomeng; Sun, Yongle; Zhou, Heyi; Huang, Fang

    2013-11-01

    The genome of unicellular green alga Chlamydomonas reinhardtii contains four genes encoding B-type methionine sulfoxide reductases, MSRB1.1, MSRB1.2, MSRB2.1, and MSRB2.2, with functions largely unknown. To understand the cell defense system mediated by the methionine sulfoxide reductases in Chlamydomonas, we analyzed expression and physiological roles of the MSRBs under different abiotic stress conditions using immunoblotting and quantitative polymerase chain reaction (PCR) analyses. We showed that the MSRB2.2 protein was accumulated in cells treated with high light (1,300 µE/m² per s), whereas MSRB1.1 was accumulated in the cells under 1 mmol/L H₂O₂ treatment or sulfur depletion. We observed that the cells with the MSRB2.2 knockdown and overexpression displayed increased and decreased sensitivity to high light, respectively, based on in situ chlorophyll a fluorescence measures. We also observed that the cells with the MSRB1.1 knockdown and overexpression displayed decreased and increased tolerance to sulfur-depletion and oxidative stresses, respectively, based on growth and H₂-producing performance. The physiological implications revealed from the experimental data highlight the importance of MSRB2.2 and MSRB1.1 in protecting Chlamydomonas cells against adverse conditions such as high-light, sulfur-depletion, and oxidative stresses.

  11. The role of nonmagnetic d0 vs. d10B-type cations on the magnetic exchange interactions in osmium double perovskites

    NASA Astrophysics Data System (ADS)

    Feng, Hai L.; Yamaura, Kazunari; Tjeng, Liu Hao; Jansen, Martin

    2016-11-01

    Polycrystalline samples of double perovskites Ba2BOsO6 (B=Sc, Y, In) were synthesized by solid state reactions. They adopt the cubic double perovskite structures (space group, Fm-3m) with ordered B and Os arrangements. Ba2BOsO6 (B=Sc, Y, In) show antiferromagnetic transitions at 93 K, 69 K, and 28 K, respectively. The Weiss-temperatures are -590 K for Ba2ScOsO6, -571 K for Ba2YOsO6, and -155 K for Ba2InOsO6. Sc3+ and Y3+ have the open-shell d0 electronic configuration, while In3+ has the closed-shell d10. This indicates that a d0 B-type cation induces stronger overall magnetic exchange interactions in comparison to a d10. Comparison of Ba2BOsO6 (B=Sc, Y, In) to their Sr and Ca analogues shows that the structural distortions weaken the overall magnetic exchange interactions.

  12. Commercial-scale recycling of NdFeB-type magnets with grain boundary modification yields products with 'designer properties' that exceed those of starting materials.

    PubMed

    Zakotnik, M; Tudor, C O

    2015-10-01

    NdFeB-type magnets dominate the market for high performance magnetic materials, yet production of 'virgin' magnets via mining is environmentally, financially and energetically costly. Hence, interest is growing in 'magnet to magnet' recycling schemes that offer the potential for cheaper, more environmentally-friendly solutions to the world's growing appetite for rare-earth based magnetic materials. Unfortunately, previously described recycling processes only partially capitalise on this potential, because the methods described to date are limited to 'laboratory scale' or operate only under ideal conditions and result in products that fail to recapture the coercivity of the starting, scrap materials. Herein, we report a commercial scale process (120 kg batches) that completely recovers the properties of the starting scrap magnets. Indeed, 'grain boundary modification', via careful addition of a proprietary mix of blended elements, produces magnets with 'designer properties' that can exceed those of the starting materials and can be closely tailored to meet a wide variety of end-user applications, including high-coercivity (>2000 kA/m), sintered magnets suitable for motor applications.

  13. Chronic psychosocial stress in male mice causes an up-regulation of scavenger receptor class B type 1 protein in the adrenal glands.

    PubMed

    Füchsl, Andrea M; Uschold-Schmidt, Nicole; Reber, Stefan O

    2013-07-01

    Mice exposed to chronic subordinate colony housing (CSC, 19 days) show an exaggerated adrenal corticosterone response to an acute heterotypic stressor (elevated platform (EPF), 5 min) despite no difference from EPF-exposed single-housed control (SHC) mice in corticotropin (ACTH) secretion. In the present study, we asked the question whether this CSC-induced increase in adrenal capability to produce and secrete corticosterone is paralleled by an enhanced adrenal availability and/or mobilization capacity of the corticosterone precursor molecule cholesterol. Employing oil-red staining and western blot analysis we revealed comparable relative density of cortical lipid droplets and relative protein expression of hormone-sensitive lipase, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and low-density lipoprotein receptor (LDL-R) between CSC and SHC mice. However, relative protein expression of the scavenger receptor class B type 1 (SR-BI) was increased following CSC exposure. Moreover, analysis of plasma high-density lipoprotein-cholesterol (HDL-C) and LDL-cholesterol (LDL-C) revealed increased LDL-C levels in CSC mice. Together with the pronounced increase in adrenal weight, evidently mediated by hyperplasia of adrenocortical cells, these data strongly indicate an enhanced adrenal availability of and capacity to mobilize cholesterol in chronic psychosocially-stressed mice, contributing to their increased in vivo corticosterone response during acute heterotypic stressor exposure.

  14. Solitons, Bäcklund transformation and Lax pair for a (2+1)-dimensional B-type Kadomtsev-Petviashvili equation in the fluid/plasma mechanics

    NASA Astrophysics Data System (ADS)

    Lan, Zhong-Zhou; Gao, Yi-Tian; Yang, Jin-Wei; Su, Chuan-Qi; Wang, Qi-Min

    2016-09-01

    Under investigation in this paper is a (2+1)-dimensional B-type Kadomtsev-Petviashvili equation for the shallow water wave in a fluid or electrostatic wave potential in a plasma. Bilinear form, Bäcklund transformation and Lax pair are derived based on the binary Bell polynomials. Multi-soliton solutions are constructed via the Hirota’s method. Propagation and interaction of the solitons are illustrated graphically: (i) Through the asymptotic analysis, elastic and inelastic interactions between the two solitons are discussed analytically and graphically, respectively. The elastic interaction, amplitudes, velocities and shapes of the two solitons remain unchanged except for a phase shift. However, in the area of the inelastic interaction, amplitudes of the two solitons have a linear superposition. (ii) Elastic interactions among the three solitons indicate that the properties of the elastic interactions among the three solitons are similar to those between the two solitons. Moreover, oblique and overtaking interactions between the two solitons are displayed. Oblique interactions among the three solitons and interactions among the two parallel solitons and a single one are presented as well. (iii) Inelastic-elastic interactions imply that the interaction between the inelastic region and another one is elastic.

  15. Different B-type methionine sulfoxide reductases in Chlamydomonas may protect the alga against high-light, sulfur-depletion, or oxidative stress.

    PubMed

    Zhao, Lei; Chen, Mei; Cheng, Dongmei; Yang, Haomeng; Sun, Yongle; Zhou, Heyi; Huang, Fang

    2013-11-01

    The genome of unicellular green alga Chlamydomonas reinhardtii contains four genes encoding B-type methionine sulfoxide reductases, MSRB1.1, MSRB1.2, MSRB2.1, and MSRB2.2, with functions largely unknown. To understand the cell defense system mediated by the methionine sulfoxide reductases in Chlamydomonas, we analyzed expression and physiological roles of the MSRBs under different abiotic stress conditions using immunoblotting and quantitative polymerase chain reaction (PCR) analyses. We showed that the MSRB2.2 protein was accumulated in cells treated with high light (1,300 µE/m² per s), whereas MSRB1.1 was accumulated in the cells under 1 mmol/L H₂O₂ treatment or sulfur depletion. We observed that the cells with the MSRB2.2 knockdown and overexpression displayed increased and decreased sensitivity to high light, respectively, based on in situ chlorophyll a fluorescence measures. We also observed that the cells with the MSRB1.1 knockdown and overexpression displayed decreased and increased tolerance to sulfur-depletion and oxidative stresses, respectively, based on growth and H₂-producing performance. The physiological implications revealed from the experimental data highlight the importance of MSRB2.2 and MSRB1.1 in protecting Chlamydomonas cells against adverse conditions such as high-light, sulfur-depletion, and oxidative stresses. PMID:24034412

  16. Metabolism of /sup 125/I-atrial natriuretic factor by vascular smooth muscle cells. Evidence for a peptidase that specifically removes the COOH-terminal tripeptide

    SciTech Connect

    Johnson, G.R.; Arik, L.; Foster, C.J.

    1989-07-15

    The addition of 200 pM monoiodinated human atrial natriuretic factor-(99-126) (125I-hANF) to cultured bovine aortic smooth muscle cells at 37/degree/C resulted in a rapid clearance from the medium (t1/2 approximately 7.5 min). Within 5 min, (125I)iodotyrosine126 (125I-Y), Arg125-(125I)iodotyrosine126 (125I-RY) and Phe124-Arg-(125)iodotyrosine126 (125I-FRY) appeared in the medium. The identities of these degradation products were confirmed by (1) retention time on high performance liquid chromatography (HPLC) relative to standards, (2) products generated by digestion with aminopeptidase M, and (3) the absence of the Met110. Preincubation of the cells with ammonium chloride or chloroquine resulted in a significant increase in the intracellular accumulation of radiolabel, indicative of endocytosis and rapid delivery of 125I-hANF to an acidic intracellular compartment (endosome and/or lysosome). Neither ammonium chloride, chloroquine, nor excess unlabeled hANF blocked the rapid appearance in the medium of 125I-RY or 125I-FRY. Bestatin inhibited the generation of 125I-RY, with a concomitant increase in 125I-FRY, suggesting that the 125I-RY is produced by aminopeptidase action on 125I-FRY. The endopeptidase 24.11 (enkephalinase) inhibitor, SCH 39370, did not inhibit the formation of 125I-FRY. These results provide evidence of a peptidase capable of specifically removing the COOH-terminal tripeptide from 125I-hANF. The COOH-terminal tripeptide, Phe124-Arg-Tyr126, was also isolated from cell digests of hANF by HPLC and its identity confirmed by amino acid analysis. Since it is generally believed that the COOH-terminal tripeptide is critical to many of atrial natriuretic factor-(99-126)'s bioactivities, this enzyme may be involved in the inactivation of atrial natriuretic factor-(99-126) in target tissues.

  17. Agonistic induction of a covalent dimer in a mutant of natriuretic peptide receptor-A documents a juxtamembrane interaction that accompanies receptor activation.

    PubMed

    Labrecque, J; Deschênes, J; McNicoll, N; De Léan, A

    2001-03-16

    The natriuretic peptide receptor-A (NPR-A) is composed of an extracellular domain with a ligand binding site, a transmembrane-spanning domain, a kinase homology domain, and a guanylyl cyclase domain. In response to agonists (atrial natriuretic peptide (ANP) and brain natriuretic peptide), the kinase homology domain-mediated guanylate cyclase repression is removed, which allows the production of cyclic GMP. Previous work from our laboratory strongly indicated that agonists are exerting their effects through the induction of a juxtamembrane dimeric contact. However, a direct demonstration of this mechanism remains to be provided. As a tool, we are now using the properties of a new mutation, D435C. It introduces a cysteine at a position in NPR-A corresponding to a supplementary cysteine found in NPR-C6, another receptor of this family (a disulfide-linked dimer). Although this D435C mutation only leads to trace levels of NPR-A disulfide-linked dimer at basal state, covalent dimerization can be induced by a treatment with rat ANP or with other agonists. The NPR-A(D435C) mutant has not been subjected to significant structural alterations, since it shares with the wild type receptor a similar dose-response pattern of cellular guanylyl cyclase activation. However, a persistent activation accompanies NPR-A(D435C) dimer formation after the removal of the inducer agonist. On the other hand, a construction where the intracellular domain of NPR-A(D435C) has been truncated (DeltaKC(D435C)) displays a spontaneous and complete covalent dimerization. In addition, the elimination of the intracellular domain in wild type DeltaKC and DeltaKC(D435C) is associated with an increase of agonist binding affinity, this effect being more pronounced with the weak agonist pBNP. Also, a D435C secreted extracellular domain remains unlinked even after incubation with rat ANP. In summary, these results demonstrate, in a dynamic fashion, the agonistic induction of a dimeric contact in the

  18. Agonistic induction of a covalent dimer in a mutant of natriuretic peptide receptor-A documents a juxtamembrane interaction that accompanies receptor activation.

    PubMed

    Labrecque, J; Deschênes, J; McNicoll, N; De Léan, A

    2001-03-16

    The natriuretic peptide receptor-A (NPR-A) is composed of an extracellular domain with a ligand binding site, a transmembrane-spanning domain, a kinase homology domain, and a guanylyl cyclase domain. In response to agonists (atrial natriuretic peptide (ANP) and brain natriuretic peptide), the kinase homology domain-mediated guanylate cyclase repression is removed, which allows the production of cyclic GMP. Previous work from our laboratory strongly indicated that agonists are exerting their effects through the induction of a juxtamembrane dimeric contact. However, a direct demonstration of this mechanism remains to be provided. As a tool, we are now using the properties of a new mutation, D435C. It introduces a cysteine at a position in NPR-A corresponding to a supplementary cysteine found in NPR-C6, another receptor of this family (a disulfide-linked dimer). Although this D435C mutation only leads to trace levels of NPR-A disulfide-linked dimer at basal state, covalent dimerization can be induced by a treatment with rat ANP or with other agonists. The NPR-A(D435C) mutant has not been subjected to significant structural alterations, since it shares with the wild type receptor a similar dose-response pattern of cellular guanylyl cyclase activation. However, a persistent activation accompanies NPR-A(D435C) dimer formation after the removal of the inducer agonist. On the other hand, a construction where the intracellular domain of NPR-A(D435C) has been truncated (DeltaKC(D435C)) displays a spontaneous and complete covalent dimerization. In addition, the elimination of the intracellular domain in wild type DeltaKC and DeltaKC(D435C) is associated with an increase of agonist binding affinity, this effect being more pronounced with the weak agonist pBNP. Also, a D435C secreted extracellular domain remains unlinked even after incubation with rat ANP. In summary, these results demonstrate, in a dynamic fashion, the agonistic induction of a dimeric contact in the

  19. The value of Serum BNP for diagnosis of intracranial injury in minor head trauma

    PubMed Central

    2014-01-01

    Objective Head injury is the main cause of death among individuals younger than 45 years old. Cranial Computerized tomography (CT) is commonly used for diagnosis of head injury. Brain Natriuretic Peptide (BNP) is a peptide originally isolated from brain ventricles. The main aim of this study is to investigate BNP as an indicator of head injury among patients presenting to emergency department (ED) with minor head trauma. Methods This was a prospective study conducted at the emergency department of the Numune Training and Research Hospital. A total of 162 patients who presented to the ED with minor head injury were enrolled. The patients were categorized into 2 groups as the cranial CT-negative and positive groups. The normality of the data was tested using One Sample Kolmogorov Smirnov test. Mann–Whitney U test was used to compare 2 independent groups while the Kruskal-Wallis test was utilized for comparison of more than 2 groups. A p-value of <0.05 was considered to be significant. Results Ninety-six (59.3%) patients were male and 66 (40.7%) were female. The cranial CT-negative group had a median BNP level of 14.5 pg/ml while the cranial CT-positive group had a median BNP level of 13 pg/ml. There was no statistically significant difference between these two groups for serum BNP levels (p > 0.05). Conclusion This study suggested that serum BNP level wasn’t used in defined of intracranial injury. PMID:24512950

  20. An integrated view of redox and catalytic properties of B-type PpDyP from Pseudomonas putida MET94 and its distal variants.

    PubMed

    Mendes, Sónia; Brissos, Vânia; Gabriel, Antonieta; Catarino, Teresa; Turner, David L; Todorovic, Smilja; Martins, Lígia O

    2015-05-15

    PpDyP from Pseudomonas putida MET94 is an extremely versatile B-type dye-decolourising peroxidase (DyP) capable of efficient oxidation of a wide range of anthraquinonic and azo dyes, phenolic substrates, the non-phenolic veratryl alcohol and even manganese and ferrous ions. In reaction with H2O2 it forms a stable Compound I at a rate of (1.4±0.3)×10(6)M(-1)s(-1), comparable to those of classical peroxidases and other DyPs. We provide the first report of standard redox potential (E(0')) of the Compound I/Native redox couple in a DyP-type peroxidase. The value of E(0')Cpd I/N=1.10±0.04 (V) is similar to those found in peroxidases from the mammalian superfamily but higher than in peroxidases from the plant superfamily. Site-directed mutagenesis has been used to investigate the role of conserved distal residues, i.e. to replace aspartate 132 by asparagine, and arginine 214 and asparagine 136 by leucine. The structural, redox and catalytic properties of variants are addressed by spectroscopic, electrochemical and kinetic measurements. Our data point to the importance of the distal arginine in the catalytic mechanism of PpDyP, as also observed in DyPB from Rhodococcus jostii RHA1 but not in DyPs from the A and D subfamilies. This work reinforces the idea of existence of mechanistic variations among members of the different sub-families of DyPs with direct implications for their enzymatic properties and potential for biotechnological applications.

  1. Increased DNA methylation of scavenger receptor class B type I contributes to inhibitory effects of prenatal caffeine ingestion on cholesterol uptake and steroidogenesis in fetal adrenals.

    PubMed

    Wu, Dong-Mei; He, Zheng; Ma, Liang-Peng; Wang, Lin-Long; Ping, Jie; Wang, Hui

    2015-06-01

    Steroid hormones synthesized from cholesterol in the fetal adrenal are crucial for fetal development. We have observed the inhibited fetal adrenal corticosterone synthesis and increased intrauterine growth retardation (IUGR) rate in rats under prenatal caffeine ingestion. The aim of this study is to evaluate the effects of prenatal caffeine ingestion on cholesterol supply in fetal adrenal steroidogenesis in rats and explore the underlying epigenetic mechanisms. Pregnant Wistar rats were treated with 60 mg/kg · d caffeine from gestational day (GD) 7 to GD17. Histological changes of fetal adrenals and increased IUGR rates were observed in the caffeine group. There were significantly decreased steroid hormone contents and cholesterol supply in caffeine-treated fetal adrenals. Data from the gene expression array suggested that prenatal caffeine ingestion caused increased expression of genes related to DNA methylation and decreased expression of genes related to cholesterol uptake. The following conjoint analysis of DNA methylation array with these differentially expressed genes suggested that scavenger receptor class B type I (SR-BI) may play an important role in caffeine-induced cholesterol supply deficiency. Moreover, real-time RT-PCR and immunohistochemical detection certified the inhibitory effects of caffeine on both mRNA expression and protein expression of SR-BI in the fetal adrenal. And the increased DNA methylation frequency in the proximal promoter of SR-BI was confirmed by bisulfite-sequencing PCR. In conclusion, prenatal caffeine ingestion can induce DNA hypermethylation of the SR-BI promoter in the rat fetal adrenal. These effects may lead to decreased SR-BI expression and cholesterol uptake, which inhibits steroidogenesis in the fetal adrenal.

  2. Increased DNA methylation of scavenger receptor class B type I contributes to inhibitory effects of prenatal caffeine ingestion on cholesterol uptake and steroidogenesis in fetal adrenals

    SciTech Connect

    Wu, Dong-Mei; He, Zheng; Ma, Liang-Peng; Wang, Lin-Long; Ping, Jie; Wang, Hui

    2015-06-01

    Steroid hormones synthesized from cholesterol in the fetal adrenal are crucial for fetal development. We have observed the inhibited fetal adrenal corticosterone synthesis and increased intrauterine growth retardation (IUGR) rate in rats under prenatal caffeine ingestion. The aim of this study is to evaluate the effects of prenatal caffeine ingestion on cholesterol supply in fetal adrenal steroidogenesis in rats and explore the underlying epigenetic mechanisms. Pregnant Wistar rats were treated with 60 mg/kg·d caffeine from gestational day (GD) 7 to GD17. Histological changes of fetal adrenals and increased IUGR rates were observed in the caffeine group. There were significantly decreased steroid hormone contents and cholesterol supply in caffeine-treated fetal adrenals. Data from the gene expression array suggested that prenatal caffeine ingestion caused increased expression of genes related to DNA methylation and decreased expression of genes related to cholesterol uptake. The following conjoint analysis of DNA methylation array with these differentially expressed genes suggested that scavenger receptor class B type I (SR-BI) may play an important role in caffeine-induced cholesterol supply deficiency. Moreover, real-time RT-PCR and immunohistochemical detection certified the inhibitory effects of caffeine on both mRNA expression and protein expression of SR-BI in the fetal adrenal. And the increased DNA methylation frequency in the proximal promoter of SR-BI was confirmed by bisulfite-sequencing PCR. In conclusion, prenatal caffeine ingestion can induce DNA hypermethylation of the SR-BI promoter in the rat fetal adrenal. These effects may lead to decreased SR-BI expression and cholesterol uptake, which inhibits steroidogenesis in the fetal adrenal. - Highlights: • Prenatal caffeine ingestion inhibits steroid hormone production in the fetal adrenal. • Prenatal caffeine ingestion inhibits cholesterol uptake in the fetal adrenal. • Prenatal caffeine

  3. Toward a chemical mechanism of proton pumping by the B-type cytochrome c oxidases: Application of Density Functional Theory to cytochrome ba3 of Thermus thermophilus

    PubMed Central

    Fee, James A.; Case, David A.; Noodleman, Louis

    2009-01-01

    A mechanism for proton pumping by the B-type cytochrome c oxidases is presented in which one proton is pumped in conjunction with the weakly-exergonic, two-electron reduction of Fe-bound O2 to the Fe-Cu bridging peroxodianion, and three protons are pumped in conjunction with the highly-exergonic, two-electron reduction of Fe(III)-−O-O−-Cu(II) to form water and the active oxidized enzyme, Fe(III)-−OH, Cu(II). The scheme is based on the active site structure of cytochrome ba3 from Thermus thermophilus, which is considered to be both necessary and sufficient for coupled O2 reduction and proton pumping when appropriate gates are in place (not included in the model). Fourteen detailed structures obtained from DFT geometry optimization are presented that are reasonably thought to occur during the four-electron reduction of O2. Each proton pumping step takes place when a proton resides on the imidazole ring of I-His376 and the large active site cluster has a net charge of +1 due to an uncompensated, positive charge formally associated with CuB. Density functional theory (DFT) of four types was applied to determine the energy of each intermediate, and standard thermochemical approaches were used to obtain the reaction free energies for each step in the catalytic cycle. This application of DFT generally conforms with previously suggested criteria for a valid model [P. E. M. Siegbahn & M. A. R. Blomberg (2000) 100 421 - 437] and, shows how the chemistry of O2-reduction in the heme a3-CuB dinuclear center can be harnessed to generate an electrochemical proton gradient across the lipid bilayer. PMID:18928258

  4. Quantitative Studies of the Far-Ultraviolet, Ultraviolet, and Optical Spectra of Late O- and Early B-Type Supergiants in the Magellanic Clouds

    NASA Astrophysics Data System (ADS)

    Evans, C. J.; Crowther, P. A.; Fullerton, A. W.; Hillier, D. J.

    2004-08-01

    We present quantitative studies of eight late O- and early B-type supergiants in the Magellanic Clouds using far-ultraviolet Far Ultraviolet Spectroscopic Explorer, ultraviolet International Ultraviolet Explorer/Hubble Space Telescope, and optical VLT-UVES spectroscopy. Temperatures, mass-loss rates, and CNO abundances are obtained using the non-LTE, spherical, line-blanketed model atmosphere code of Hillier & Miller. We support recent results for lower temperatures of OB-type supergiants as a result of stellar winds and blanketing, which amounts to ~2000 K at B0 Ia. In general, Hα-derived mass-loss rates are consistent with UV and far-UV spectroscopy, although from consideration of the S IV λλ1063, 1073 doublet, clumped winds are preferred over homogenous models. AV 235 (B0 Iaw) is a notable exception, which has an unusually strong Hα profile that is inconsistent with the other Balmer lines and UV wind diagnostics. We also derive CNO abundances for our sample, revealing substantial nitrogen enrichment, with carbon and oxygen depletion. Our results are supported by comparison with the Galactic supergiant HD 2905 (BC0.7 Ia) for which near-solar CNO abundances are obtained. This bolsters previous suggestions that ``normal'' OB-type supergiants exhibit atmospheric compositions indicative of partial CNO processing. Based on observations made with the NASA-CNES-CSA Far Ultraviolet Spectroscopic Explorer. FUSE is operated by Johns Hopkins University under NASA contract NAS5-32985. Also based in part on observations collected at the European Southern Observatory Very Large Telescope in program 67.D-0238, plus archival data obtained with the NASA-ESA Hubble Space Telescope and the NASA-ESA-PPARC International Ultraviolet Explorer.

  5. Coxsackievirus group B type 3 infection upregulates expression of monocyte chemoattractant protein 1 in cardiac myocytes, which leads to enhanced migration of mononuclear cells in viral myocarditis.

    PubMed

    Shen, Yan; Xu, Wei; Chu, Yi-Wei; Wang, Ying; Liu, Quan-Sheng; Xiong, Si-Dong

    2004-11-01

    Coxsackievirus group B type 3 (CVB3) is an important cause of viral myocarditis. The infiltration of mononuclear cells into the myocardial tissue is one of the key events in viral myocarditis. Immediately after CVB3 infects the heart, the expression of chemokine(s) by infected myocardial cells may be the first trigger for inflammatory infiltration and immune response. However, it is unknown whether CVB3 can induce the chemokine expression in cardiac myocytes. Monocyte chemoattractant protein 1 (MCP-1) is a potent chemokine that stimulates the migration of mononuclear cells. The objective of the present study was to investigate the effect of CVB3 infection on MCP-1 expression in murine cardiac myocytes and the role of MCP-1 in migration of mononuclear cells in viral myocarditis. Our results showed that the expression of MCP-1 was significantly increased in cardiac myocytes after wild-type CVB3 infection in a time- and dose-dependent manner, which resulted in enhanced migration of mononuclear cells in mice with viral myocarditis. The migration of mononuclear cells was partially abolished by antibodies specific for MCP-1 in vivo and in vitro. Administration of anti-MCP-1 antibody prevented infiltration of mononuclear cells bearing the MCP-1 receptor CCR2 in mice with viral myocarditis. Infection by UV-irradiated CVB3 induced rapid and transient expression of MCP-1 in cardiac myocytes. In conclusion, our results indicate that CVB3 infection stimulates the expression of MCP-1 in myocardial cells, which subsequently leads to migration of mononuclear cells in viral myocarditis. PMID:15507642

  6. Atrial natriuretic peptide inhibits the expression of tissue factor and plasminogen activator inhibitor 1 induced by angiotensin II in cultured rat aortic endothelial cells.

    PubMed

    Yoshizumi, M; Tsuji, H; Nishimura, H; Kasahara, T; Sugano, T; Masuda, H; Nakagawa, K; Nakahara, Y; Kitamura, H; Yamada, K; Yoneda, M; Sawada, S; Nakagawa, M

    1998-03-01

    The pharmacological characteristics of atrial natriuretic peptide (ANP), such as natriuresis, vasodilation, or suppression of smooth muscle cell proliferation, are well investigated. However, this is the first study to report its role on blood coagulation and fibrinolysis mediated by vascular endothelial cells. In this study, the effects of ANP on the enhanced expression of tissue factor (TF) and plasminogen activator inhibitor 1 (PAI-1) by angiotensin II (Ang II) in cultured rat aortic endothelial cells (RAECs) were examined. The expressions of TF and PAI-1 mRNA were detected by northern blotting methods. The activities of TF on the surface of RAECs and PAI-1 in the culture media were measured by chromogenic assay. ANP suppressed mRNA expressions of TF and PAI-1 induced by Ang II in a concentration-dependent manner. This suppression was accompanied by the decreased activities of TF and PAI-1.

  7. Association of restriction fragment length polymorphism at the atrial natriuretic peptide gene locus with aldosterone responsiveness to angiotensin in aldosterone-producing adenoma.

    PubMed

    Tunny, T J; Jonsson, J R; Klemm, S A; Ballantine, D M; Stowasser, M; Gordon, R D

    1994-11-15

    Primary aldosteronism is an important, potentially curable, form of hypertension. We examined the possible association between restriction fragment length polymorphisms in the atrial natriuretic peptide (ANP) gene and responsiveness of aldosterone to angiotensin II in 59 patients with primary aldosteronism due to aldosterone-producing adenoma (APA). Significant differences in the allelic frequencies of the BglI, TaqI and XhoI polymorphic sites at the ANP gene locus (chromosome 1; 1p36) between angiotensin II-unresponsive and angiotensin II-responsive tumors were observed. Variation in the ANP gene between the two groups may result in altered expression of ANP within the adrenal gland, and may contribute to the biochemical regulation of aldosterone production of these two subgroups of patients with APA.

  8. Immunoreactive prohormone atrial natriuretic peptides 1-30 and 31-67 - Existence of a single circulating amino-terminal peptide

    NASA Technical Reports Server (NTRS)

    Chen, Yu-Ming; Whitson, Peggy A.; Cintron, Nitza M.

    1990-01-01

    Sep-Pak C18 extraction of human plasma and radioimmunoassay using antibodies which recognize atrial natriuretic peptide (99-128) and the prohormone sequences 1-30 and 31-67 resulted in mean values from 20 normal subjects of 26.2 (+/- 9.2), 362 (+/- 173) and 368 (+/- 160) pg/ml, respectively. A high correlation coefficient between values obtained using antibodies recognizing prohormone sequences 1-30 and 31-67 was observed (R = 0.84). Extracted plasma immunoreactivity of 1-30 and 31-67 both eluted at 46 percent acetonitrile. In contrast, chromatographic elution of synthetic peptides 1-30 and 31-67 was observed at 48 and 39 percent acetonitrile, respectively. Data suggest that the radioimmunoassay of plasma using antibodies recognizing prohormone sequences 1-30 and 31-67 may represent the measurement of a unique larger amino-terminal peptide fragment containing antigenic sites recognized by both antisera.

  9. Correlation between the compact regions predicted by the average distance map (ADM) and the biologically active sites in atrial natriuretic peptide.

    PubMed

    Kikuchi, T

    1992-10-01

    The prediction of the short-range compact regions of human atrial natriuretic peptide (alpha-hANP), one of the biologically active peptides, has been made by means of the Average Distance Map(ADM). We found out that the location of the predicted short-range compact regions is consistent with the structural units determined by the NMR analysis (Kobayashi et al., 1988). Furthermore, the short-range compact regions correspond well to the biologically active areas of atriopeptin (103-125)-amide (which is homologous peptide to alpha-hANP), detected by the glycine substitution technique (Konishi et al., 1987). The results suggest that a predicted short-range compact region can be regarded as a possible active site in a biologically active peptide.

  10. MAPK3/1 is conducive to luteinizing hormone-mediated C-type natriuretic peptide decrease in bovine granulosa cells

    PubMed Central

    YANG, Lei; WEI, Qiang; GE, Junbang; ZHAO, Xiaoe; MA, Baohua

    2015-01-01

    C-type natriuretic peptide (CNP) plays a role as an oocyte maturation inhibitor (OMI) in many species, including the bovine. However, the effects of luteinizing hormone (LH) on CNP expression and its potential mechanisms have not reported in the bovine. In the present study, we aimed to study the effects of LH on CNP expression and to illuminate the potential molecular mechanism in this process. Our results showed that LH induced epidermal growth factor receptor (EGFR) phosphorylation, mitogen-activated protein kinase3/1 (MAPK3/1) activation and CNP mRNA decrease in cultured bovine granulosa cells. Further study revealed that LH suppressed CNP expression via the MAPK3/1 signaling pathway, which was activated by the EGFR pathway. In conclusion, our research suggested that MAPK3/1 is involved in LH-mediated decrease of CNP and that this process is related to the EGFR and MAPK3/1 signal pathways. PMID:26655567

  11. Mechanism of vasodilation induced by alpha-human atrial natriuretic polypeptide in rabbit and guinea-pig renal arteries.

    PubMed Central

    Fujii, K; Ishimatsu, T; Kuriyama, H

    1986-01-01

    Effects of alpha-human atrial natriuretic polypeptide (alpha-HANP) on electrical and mechanical properties of smooth muscle cells of the guinea-pig and rabbit renal arteries and of the guinea-pig mesenteric artery were investigated. alpha-HANP (up to 10 nM) modified neither the membrane potential nor resistance of smooth muscle cells of the guinea-pig and rabbit renal arteries. In the guinea-pig mesenteric and renal arteries, alpha-HANP (up to 10 nM) had no effect on the amplitude and facilitation (mesenteric artery) or depression (renal artery) of excitatory junction potentials nor on action potentials. In the guinea-pig renal artery, alpha-HANP (up to 10 nM) had no effect on the depolarization induced by noradrenaline (NA) (up to 10 microM) but markedly inhibited NA-induced contraction. alpha-HANP (10 nM) slightly inhibited the K-induced contraction. In the rabbit renal artery, alpha-HANP (10 nM) inhibited the NA-induced contraction and to a lesser extent the K-induced contraction. In the rabbit renal artery, the effects of alpha-HANP on the release of Ca from the cellular storage by two applications of NA, and its re-storage, were investigated in Ca-free solution containing 2 mM-EGTA. When 5 nM-alpha-HANP was applied before and during the first application of 0.5 microM-NA, the contraction was markedly inhibited but the contraction to a second application of 10 microM-NA was potentiated. If the first dose of NA was 10 microM the effect was very small. Under the same experimental procedures, nitroglycerine (10 microM) showed almost the same effects as alpha-HANP on the NA-induced contractions. When both the first (3 mM) and second (10 mM) contractions were evoked by caffeine in Ca-free solution, alpha-HANP (5 nM) and nitroglycerine (10 microM) inhibited both contractions to the same extent. In the rabbit renal artery, applications of alpha-HANP or nitroglycerine increased the amount of guanosine 3',5'-phosphate (cyclic GMP) in a dose-dependent manner. However, a

  12. Prognostic Importance of Exercise Brain Natriuretic Peptide in Asymptomatic Chronic Organic Severe Mitral Regurgitation: An Observational Study

    PubMed Central

    Sinha, Santosh Kumar; Garg, Shalini; Thakur, Ramesh; Krishna, Vinay; Singh, Karandeep; Sachan, Mohit; Goel, Amit; Razi, Mahamdula; Pandey, Umeshwar; Varma, Chandra Mohan

    2016-01-01

    Background The optimal timing of surgery in patients with chronic organic severe mitral regurgitation (MR) continues to be debated, especially for those who are asymptomatic. The aim of the study was to determine independent and additive prognostic value of exercise brain natriuretic peptide (eBNP) in patients with severe asymptomatic MR and normal left ventricular ejection fraction (LVEF). Methods Two hundred twenty-three consecutive patients with severe MR defined by effective regurgitant orifice (ERO) area ≥ 40 mm2 and/or residual volume ≥ 60 mL, LVEF > 60%, and normal LV end-systolic diameter < 40 mm underwent symptom limited exercise treadmill test (TMT). Echocardiography was done immediately after exercise. Data were obtained within 3 minutes of peak exercise. BNP levels were assessed before echo (after 30 minutes of supine rest) and at exercise (i.e., within the 3 minutes of the end of effort). Patients were followed up every 3 months up to 15 months for major adverse cardiac events (MACEs) (cardiovascular death, need for mitral valve surgery and hospitalization for acute pulmonary edema or heart failure). Results Mean age was 31.2 ± 9 years (range: 18 - 40) with majority being male (n = 153; 68%). Etiologies were rheumatic (n = 201; 90%), mitral valve prolapse (n = 17; 7.6%) and hypertrophic cardiomyopathy (n = 5; 2.4%). BNP level significantly increased from rest (65.24 ± 43.92 pg/mL; median: 43.5 pg/mL) to exercise (100.24 ± 98.24 pg/mL; median: 66.5 pg/mL; P < 0.001). Patients were divided into three tertiles according to eBNP levels (T1 = 15 - 44; T2 = 45 - 104; T3 = 105 - 400). There was trend for significantly lower exercise time in T3. During TMT, 66 (29.5%) stopped exercise due to dyspnea. They had similar resting BNP level compared with others but had significantly higher eBNP level (136 ± 109.7 pg/mL vs. 84.88 ± 90.2 pg/mL; P < 0.001). During follow-up (15 months), MACE occurred in 83 patients (37.2%): mitral valve replacement (MVR) in 59

  13. Role of FQQI motif in the internalization, trafficking, and signaling of guanylyl-cyclase/natriuretic peptide receptor-A in cultured murine mesangial cells.

    PubMed

    Mani, Indra; Garg, Renu; Pandey, Kailash N

    2016-01-01

    Binding of the cardiac hormone atrial natriuretic peptide (ANP) to transmembrane guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA), produces the intracellular second messenger cGMP in target cells. To delineate the critical role of an endocytic signal in intracellular sorting of the receptor, we have identified a FQQI (Phe(790), Gln(791), Gln(792), and Ile(793)) motif in the carboxyl-terminal region of NPRA. Mouse mesangial cells (MMCs) were transiently transfected with the enhanced green fluorescence protein (eGFP)-tagged wild-type (WT) and mutant constructs of eGFP-NPRA. The mutation FQQI/AAAA, in the eGFP-NPRA cDNA sequence, markedly attenuated the internalization of mutant receptors by almost 49% compared with the WT receptor. Interestingly, we show that the μ1B subunit of adaptor protein-1 binds directly to a phenylalanine-based FQQI motif in the cytoplasmic tail of the receptor. However, subcellular trafficking indicated that immunofluorescence colocalization of the mutated receptor with early endosome antigen-1 (EEA-1), lysosome-associated membrane protein-1 (LAMP-1), and Rab 11 marker was decreased by 57% in early endosomes, 48% in lysosomes, and 42% in recycling endosomes, respectively, compared with the WT receptor in MMCs. The receptor containing the mutated motif (FQQI/AAAA) also produced a significantly decreased level of intracellular cGMP during subcellular trafficking than the WT receptor. The coimmunoprecipitation assay confirmed a decreased level of colocalization of the mutant receptor with subcellular compartments during endocytic processes. The results suggest that the FQQI motif is essential for the internalization and subcellular trafficking of NPRA during the hormone signaling process in intact MMCs.

  14. MicroRNAs 125a and 455 Repress Lipoprotein-Supported Steroidogenesis by Targeting Scavenger Receptor Class B Type I in Steroidogenic Cells

    PubMed Central

    Hu, Zhigang; Shen, Wen-Jun; Kraemer, Fredric B.

    2012-01-01

    We sought to identify and characterize microRNA (miRNAs) that posttranscriptionally regulate the expression of scavenger receptor class B type I (SR-BI) and SR-BI-linked selective high-density lipoprotein (HDL) cholesteryl ester (CE) transport and steroidogenesis. Four miRNAs (miRNA-125a, miRNA-125b, miRNA-145, and miRNA-455) with a potential to regulate SR-BI were identified in silico and validated by quantitative real-time PCR (qRT-PCR), Western blot analysis, and SR-BI 3′ untranslated region (UTR) reporter assays. In vitro treatment of primary rat granulosa cells and MLTC-1 cells with cyclic AMP (cAMP) or in vivo treatment of rat adrenals with adrenocorticotropic hormone (ACTH) decreased the expression of miRNA-125a, miRNA-125b, and miRNA-455 and reciprocally increased SR-BI expression. Using luciferase constructs containing the 3′ untranslated region of SR-BI combined with miRNA overexpression and mutagenesis, we have provided evidence that steroidogenic SR-BI is a direct target of miRNA-125a and miRNA-455. Moreover, the transfection of Leydig tumor cells with precursor miRNA 125a (pre-miRNA-125a) or pre-miRNA-455 resulted in the suppression of SR-BI at both the transcript and protein levels and reduced selective HDL CE uptake and HDL-stimulated progesterone production. Transfection of liver Hepa 1-6 cells with pre-miRNA-125a significantly reduced SR-BI expression and its selective transport function. In contrast, overexpression of miRNA-145 did not affect SR-BI expression or selective HDL CE uptake mediated by SR-BI in steroidogenic cell lines. These data suggest that a trophic hormone and cAMP inversely regulate the expression of SR-BI and miRNA-125a and miRNA-455 in steroidogenic tissues/cells and that both miRNA-125a and miRNA-455, by targeting steroidogenic SR-BI, negatively regulate selective HDL CE uptake and HDL CE-supported steroid hormone production. PMID:23045399

  15. Piezoelectric microcantilever serum protein detector

    NASA Astrophysics Data System (ADS)

    Capobianco, Joseph A.

    The development of a serum protein detector will provide opportunities for better screening of at-risk cancer patients, tighter surveillance of disease recurrence and better monitoring of treatment. An integrated system that can process clinical samples for a number of different types of biomarkers would be a useful tool in the early detection of cancer. Also, screening biomarkers such as antibodies in serum would provide clinicians with information regarding the patient's response to treatment. Therefore, the goal of this study is to develop a sensor which can be used for rapid, all-electrical, real-time, label-fee, in-situ, specific quantification of cancer markers, e.g., human epidermal receptor 2 (Her2) or antibodies, in serum. To achieve this end, piezoelectric microcantilever sensors (PEMS) were constructed using an 8 mum thick lead magnesium niobate-lead titanate (PMN-PT) freestanding film as the piezoelectric layer. The desired limit of detection is on the order of pg/mL. In order to achieve this goal the higher frequency lateral extension modes were used. Also, as the driving and sensing of the PEMS is electrical, the PEMS must be insulated in a manner that allows it to function in aqueous solutions. The insulation layer must also be compatible with standardized bioconjugation techniques. Finally, detection of both cancer antigens and antibodies in serum was carried out, and the results were compared to a standard commercialized protocol. PEMS have demonstrated the capability of detecting Her2 at a concentration of 5 pg/mL in diluted human serum (1:40) in less than 1 hour. The approach can be easily translated into the clinical setting because the sensitivity is more than sufficient for monitoring prognosis of breast cancer patients. In addition to Her2 detection, antibodies in serum were assayed in order to demonstrate the feasibility of monitoring the immune response for antibody-dependent cellular cytotoxicity (ADCC) in patients on antibody therapies

  16. An aberrant adenylate kinase isoenzyme from the serum of patients with Duchenne muscular dystrophy.

    PubMed

    Hamada, M; Okuda, H; Oka, K; Watanabe, T; Ueda, K; Nojima, M; Kuby, S A; Manship, M; Tyler, F H; Ziter, F A

    1981-08-13

    The sera from patients with human Duchenne (X-linked) progressive muscular dystrophy contain elevated adenylate kinase (ATP: AMP phosphotransferase, EC 2.7.4.3) activities, in addition to their characteristically high creatine kinase (ATP; creatine N-phosphotransferase, EC 2.7.3.2) activities. By agarose gel electrophoresis of human Duchenne dystrophic serum, the presence of an apparently normal human serum adenylate kinase together with a variant species of adenylate kinase was detected. The latter enzyme species appeared, in its mobility, to be similar to that of the normal human liver-type adenylate kinase. The presence of this aberrant liver-type adenylate kinase could also be demonstrated by characteristic (for the liver type) inhibition patterns with P1,P5-di-(adenosine-5')pentaphosphate, 5,5'-dithiobis(2-nitrobenzoate) and phosphoenolpyruvate. On the other hand, by inhibition titrations with an anti-muscle-type adenylate kinase, hemolysates from the erythrocytes of several Duchenne and Becker's dystrophics were found to contain approx. 96% muscle-type adenylate kinase and their serum approx. 97% muscle-type adenylate kinase. These same patients contained approx. 89% M-M type creatine kinase in their serum (by inhibition against anti-human muscle-type creatine kinase) indicative of the presence also of M-B plus B-B type active isoenzymes. All of these data can best be explained by the presence of a variant or mutant adenylate kinase isoenzyme in the dystrophic serum. This isoenzyme appears to resemble the liver type in its inhibition patterns with P1,P5-di(adenosine-5')pentaphosphate, 5,5'-dithiobis(2-nitrobenzoate) and phosphoenolpyruvate, and in its heat stability (compare also the agarose gel electrophoresis pattern); but structurally, it is a muscle type, or derived from a muscle type, as shown immunologically by inhibition reactions with anti-muscle-type adenylate kinase. Whether this is a fetal-type isoenzyme of adenylate kinase will require further

  17. In vitro culture of coxsackievirus group B, type 3 immune spleen cells on infected endothelial cells and biological activity of the cultured cells in vivo.

    PubMed Central

    Huber, S A; Job, L P; Woodruff, J F

    1984-01-01

    Spleen cells from male BALB/c mice infected 7 days earlier by an intraperitoneal injection of 3 X 10(4) PFU of a myocarditic strain of coxsackievirus B-3 lysed virus-infected endothelial cells in a 51Cr release assay. Cytotoxic activity in the in vivo sensitized spleen cell population could be further increased by culturing the immune spleen cells from infected mice on virus-infected or uninfected endothelial cells for 6 to 7 days in vitro. Cytotoxicity of in vitro cultured spleen cells to infected targets was mediated by T lymphocytes since reactivity was abolished by treatment of the spleen cells with anti-thy 1.2 serum and complement. Reciprocal assays with BALB/c and C57BL cells indicated that maximum cytotoxicity occurred when spleen cells were sensitized on syngeneic endothelial cells. Other experiments showed that spleen cells sensitized to coxsackievirus B-3 or encephalomyocarditis virus were selectively cytolytic to targets infected with the homologous virus. Adoptive transfer of T cells cultured in vitro on infected endothelial cells retained their ability to induce myocarditis in T-lymphocyte-deficient mice. Images PMID:6319285

  18. Serum bile acids in hepatobiliary disease.

    PubMed Central

    Bouchier, I A; Pennington, C R

    1978-01-01

    We review the estimation of total and individual serum bile acids to detect the presence and nature of hepatobiliary disease. The different methods for measuring serum bile acids are discussed. PMID:355064

  19. Association between Obstructive Sleep Apnea and Elevated Levels of Type B Natriuretic Peptide in a Community-Based Sample of Women

    PubMed Central

    Ljunggren, Mirjam; Lindahl, Bertil; Theorell-Haglöw, Jenny; Lindberg, Eva

    2012-01-01

    Study Objectives: Obstructive sleep apnea (OSA) is associated with an increased risk of cardiovascular disease. One contributory factor may be hemodynamic stress due to the negative intrathoracic pressure during each episode of apnea. Type B natriuretic peptide (BNP) is secreted by the cardiac ventricles in response to volume expansion and pressure load and the authors hypothesized that there would be an association between indices of OSA during the night and levels of BNP in the morning. Setting: Community-based in Uppsala, Sweden. Participants: There were 349 women who participated. Measurements and Results: Participants underwent full-night polysomnography and anthropometric measurements, and answered questionnaires about medical conditions and current medication. The morning after the polysomnography, blood samples were drawn for analysis of plasma BNP, C-reactive protein, creatinine, and hemoglobin. There was an increase in mean BNP as the severity of sleep apnea increased, increasing from a mean value of 8.5 ng/L among women with an apnea-hypopnea index (AHI) < 5 to 18.0 ng/L in women with an AHI ≥ 30. Elevated BNP levels (≥ 20 ng/L) were found in 29.8% of the women, whereas 70.2% had normal levels. The odds ratio was 2.2 for elevated BNP levels for women with an AHI of 5–14.9 in relation to women with an AHI < 5, 3.1 for women with an AHI of 15–29.9, and 4.6 for women with an AHI ≥ 30 after adjustment for age, body mass index, systolic blood pressure, antihypertensive drugs, and creatinine. Conclusions: There is a dose-response relationship in women between the severity of sleep apnea during the night and the levels of BNP in the morning. Citation: Ljunggren M; Lindahl B; Theorell-Haglöw J; Lindberg E. Association between obstructive sleep apnea and elevated levels of type B natriuretic peptide in a community-based sample of women. SLEEP 2012;35(11):1521-1527. PMID:23115401

  20. 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

  1. Serum Survivin Increases in Prolactinoma

    PubMed Central

    Dellal, Fatma Dilek; Niyazoglu, Mutlu; Gorar, Suheyla; Ademoglu, Esranur; Candan, Zehra; Bekdemir, Handan; Hacioglu, Yalcin; Kaya, Fatih Oner

    2015-01-01

    Background Prolactinoma is the most common adult pituitary adenoma. Survivin is a member of the family of inhibitors of apoptosis proteins. Its expression is observed in many tumors. Survivin expression has shown in prolactinoma tissue before but no study exists showing serum survivin level. The aim of the present study was to investigate serum survivin levels in patients with prolactinoma and demonstrate its value in diagnosis of the disease. Methods The group of patients consisted of 25 women, aged from 17 to 51 years. As a control group, 21 healthy women, aged from 22 to 45 years were included. Twenty patients had microprolactinoma, while five patients had macroprolactinoma. All patients had received dopamine agonist treatment. Serum survivin levels were measured in all of the groups. Results Survivin levels were significantly higher in prolactinoma patients compared to controls (19.04 (10 - 38) pg/mL; 15.05 (8 - 22) pg/mL; P = 0.042). There was no difference between microadenoma and macroadenoma patients in survivin levels (19.22 (10 - 38) pg/mL; 18.40 (16 - 22) pg/mL; P = 0.914). In correlation analysis, survivin was not correlated with other parameters. Conclusions We consider that higher survivin levels might be a molecular marker predicting the presence of prolactinoma and may be useful for the diagnosis. But large-scale research is needed to clarify its role in diagnosis of prolactinoma patients. PMID:25699121

  2. Possible involvement of central C-type natriuretic polypeptide receptor on water intake in spontaneously hypertensive rats, but not in normotensive Wistar-Kyoto rats.

    PubMed

    Shibata, K; Makino, I; Goto, E; Katsuragi, T; Furukawa, T

    1999-12-01

    The present study was designed to examine the possible role of brain C-type natriuretic polypeptide receptor (GC-B) in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto rats (WKY). The level of GC-B mRNA in various regions of the brain in both SHR and WKY was examined in the present study. The GC-B mRNA was unevenly distributed in rat brain, the transcript being expressed predominantly in the hypothalamus and cerebellum but comparatively at low level in the striatum and septum. However, the level in the septum was 3-fold higher in SHR than than in age-matched WKY, while no differences were observed in other regions of the brain. Intracerebroventricular administration of antisense oligonucleotide to GC-B mRNA inhibits the night-time water intake in SHR, but not in WKY. However, the daily food intake was not significantly altered by the injection of antisense oligonucleotide in both strains. These results demonstrate that the brain GC-B mRNA, particularly in septum, is increased in SHR and this increase may be closely related to the regulation of water-drinking behaviour in SHR.

  3. Inhibitory effects of C-type natriuretic peptide on the differentiation of cardiac fibroblasts, and secretion of monocyte chemoattractant protein-1 and plasminogen activator inhibitor-1.

    PubMed

    Li, Zhi-Qiang; Liu, Ying-Long; Li, Gang; Li, Bin; Liu, Yang; Li, Xiao-Feng; Liu, Ai-Jun

    2015-01-01

    The present study aimed to investigate the effect of C-type natriuretic peptide (CNP) on the function of cardiac fibroblasts (CFs). Western blotting was used to investigate the expression of myofibroblast marker proteins: α-smooth muscle actin (α-SMA), extra domain-A fibronectin, collagen I and collagen III, and the activity of extracellular signal-regulated kinase 1/2 (ERK1/2). Immunofluorescence was used to examine the morphological changes; a transwell assay was used to analyze migration, and reverse transcription-quantitative polymerase chain reaction and ELISA were employed to determine the mRNA expression and protein secretion of monocyte chemoattractant protein-1 (MCP-1) and plasminogen activator inhibitor-1 (PAI-1). The results demonstrated that CNP significantly reduced the protein expression of α-SMA, fibronectin, collagen I and collagen III, and suppressed the migratory ability of CFs. Additionally, the mRNA and protein expression of MCP-1 and PAI-1 was inhibited under the CNP treatment; and this effect was mediated by the inhibition of the ERK1/2 activity. In conclusion, CNP inhibited cardiac fibroblast differentiation and migration, and reduced the secretion of MCP-1 and PAI-1, which demonstrates novel mechanisms to explain the antifibrotic effect of CNP.

  4. An activator of protein kinase C (phorbol dibutyrate) attenuates atrial-natriuretic-factor-stimulated cyclic GMP accumulation in smooth-muscle cells.

    PubMed Central

    Nambi, P; Whitman, M; Aiyar, N; Stassen, F; Crooke, S T

    1987-01-01

    Rat thoracic aortic smooth-muscle cells (A-10; A.T.C.C. CRL 1476) displays a high density of vasopressin and atrial-natriuretic-factor (ANF) receptors and a low density of beta-adrenergic receptors. ANF stimulates cGMP (cyclic GMP) accumulation in a time- and dose-dependent fashion. Pretreatment of these cells with phorbol dibutyrate (PDBu), a known activator of protein kinase C, attenuated ANF-stimulated cGMP accumulation without affecting basal cGMP concentrations. This effect was concentration-dependent and was observed as early as 2 min after treatment. 4 alpha-Phorbol 12, 13-didecanoate (alpha PDD), which does not activate protein kinase C, did not inhibit the cGMP accumulation. PDBu pretreatment did not affect the density and affinity of ANF receptors. These data suggest that PDBu, presumably via activation of protein kinase C, might stimulate phosphorylation of a key regulatory protein in the ANF/cGMP pathway. PMID:2822009

  5. Activation of IKK/NF-κB provokes renal inflammatory responses in guanylyl cyclase/natriuretic peptide receptor-A gene-knockout mice

    PubMed Central

    Das, Subhankar; Periyasamy, Ramu

    2012-01-01

    The present study was aimed at determining the consequences of the disruption of guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) gene (Npr1) on proinflammatory responses of nuclear factor kappa B, inhibitory kappa B kinase, and inhibitory kappa B alpha (NF-κB, IKK, IκBα) in the kidneys of mutant mice. The results showed that the disruption of Npr1 enhanced the renal NF-κB binding activity by 3.8-fold in 0-copy (−/−) mice compared with 2-copy (+/+) mice. In parallel, IKK activity and IκBα protein phosphorylation were increased by 8- and 11-fold, respectively, in the kidneys of 0-copy mice compared with wild-type mice. Interestingly, IκBα was reduced by 80% and the expression of proinflammatory cytokines and renal fibrosis were significantly enhanced in 0-copy mice than 2-copy mice. Treatment of 0-copy mice with NF-κB inhibitors andrographolide, pyrrolidine dithiocarbamate, and etanercept showed a substantial reduction in renal fibrosis, attenuation of proinflammatory cytokines gene expression, and significantly reduced IKK activity and IkBα phosphorylation. These findings indicate that the systemic disruption of Npr1 activates the renal NF-κB pathways in 0-copy mice, which transactivates the expression of various proinflammatory cytokines to initiate renal remodeling; however, inhibition of NF-κB pathway repairs the abnormal renal pathology in mutant mice. PMID:22318993

  6. Atrial natriuretic peptide in the locus coeruleus and its possible role in the regulation of arterial blood pressure, fluid and electrolyte homeostasis

    SciTech Connect

    Geiger, H.; Sterzel, R.B. ); Bahner, U.; Heidland, A. ); Palkovits, M. )

    1991-01-01

    Atrial natriuretic factor (ANP) is present in neuronal cells of the locus coeruleus and its vicinity in the pontine tegmentum and moderate amount of ANP is detectable in this area by radioimmunoassay. The ANP is known as a neuropeptide which may influence the body salt and water homeostasis and blood pressure by targeting both central and peripheral regulatory mechanisms. Whether this pontine ANP cell group is involved in any of these regulatory mechanisms, the effect of various types of hypertension and experimental alterations in the salt and water balance on ANP levels was measured by radioimmunoassay in the locus coeruleus of rats. Adrenalectomy, as well as aldosterone and dexamethasone treatments failed to alter ANP levels in the locus coeruleus. Reduced ANP levels were measured in spontaneously hypertensive rats, and in diabetes insipidus rats with vasopressin replacement. In contrast to these situations, elevated ANP levels were found in rats with DOCA-salt or 1-Kidney-1-clip hypertension. These data suggest a link between ANP levels in the locus coeruleus and fluid volume homeostasis. Whether this link is causal and connected with the major activity of locus coeruleus neurons needs further information.

  7. Relation of brain natriuretic peptide level to extent of left ventricular scarring in patients with chronic heart failure secondary to ischemic cardiomyopathy.

    PubMed

    Aktas, Mehmet Kemal; Allen, Drew; Jaber, Wael A; Chuang, Hsuan-Hung; Taylor, David O; Yamani, Mohamad H

    2009-01-15

    Multiple factors influence brain natriuretic peptide (BNP) release in patients with heart failure. We hypothesized that extensive myocardial scarring could result in an attenuated BNP response. A total of 115 patients with New York Heart Association class III chronic heart failure and ischemic cardiomyopathy were evaluated for ischemia, hibernation, and myocardial scarring by dipyridamole-rubidium-positron emission tomographic scanning with fluorine-18, 2-fluoro-2-deoxyyglucose. Plasma BNP levels were determined within 2 weeks of the study. Left ventricular dimension and function were evaluated by echocardiography. Patients were categorized as having <33% myocardial scar (n=67) or>or=33% myocardial scar (n=48). BNP measurements were correlated with amount of myocardial scarring. Compared with patients with less scar, those with >or=33% scar had lower BNP levels (mean 317+/-364 vs 635+/-852 pg/ml, median 212 vs 357, p=0.016). Using multiple regression analysis, presence of scarring was associated with decreased BNP response (p=0.022). Further, patients with <33% scar in whom a higher BNP level was noted had more ischemia (51% vs 27%, p=0.01) and greater myocardial hibernation (22+/-14% vs 12+/-7%, p=0.02) compared with patients with >or=33% scar. In conclusion, in patients with chronic heart failure, a decreased BNP response indicated extensive myocardial scarring. PMID:19121444

  8. Measurement of cytoplasmic free Ca2+ concentration in rabbit aorta using the photoprotein, aequorin. Effect of atrial natriuretic peptide on agonist-induced Ca2+ signal generation.

    PubMed Central

    Takuwa, Y; Rasmussen, H

    1987-01-01

    Addition of norepinephrine, angiotensin II, or histamine leads to a transient rise in the cytoplasmic Ca2+ concentration ([Ca2+]i), as measured with aequorin, in rabbit aortic strips. Each induces a [Ca2+]i transient which peaks in 2 min and then falls either back to baseline (angiotensin II) or to a plateau (norepinephrine and histamine). The [Ca2+]i transient is due to the mobilization of Ca2+ from a caffeine-sensitive, intracellular pool. An elevation of [K+] to 35 mM leads to a monotonic sustained rise in [Ca2+]i which depends entirely on extracellular Ca2+, but an increase to 100 mM leads to a [Ca2+]i transient from the mobilization of intracellular Ca2+. Atrial natriuretic peptide does not alter basal [Ca2+]i nor inhibit the [Ca2+]i transient induced by either histamine or angiotensin II, but blocks that induced by norepinephrine, and blocks the plateau phase induced by either histamine or norepinephrine. The peptide inhibits the contractile response to all three agonists and to K+. PMID:2439545

  9. Change in plasma immunoreactive N-terminus, C-terminus, and 4,000-dalton midportion of atrial natriuretic factor prohormone with hemodialysis.

    PubMed

    Winters, C J; Vesely, D L

    1991-01-01

    Plasma concentrations of the immunoreactive N-terminus, C-terminus and 4,000-dalton midportion of the N-terminus of the atrial natriuretic factor (ANF) prohormone were measured before and after hemodialysis in 13 patients with end-stage renal disease. There was a significant (p less than 0.001) fall in the mean plasma concentration of the C-terminus (i.e. ANF, amino acids 99-126 of the prohormone) from 123 +/- 25 to 80 +/- 22 fmol/ml (mean +/- SEM) with dialysis. The whole N-terminus, on the other hand, increased from 9,336 +/- 2,011 to 11,021 +/- 2,134 fmol/ml after dialysis (p less than 0.002). Pro ANF 31-67 (i.e. amino acids 31-67 of the prohormone) increased postdialysis from 27,775 +/- 4,300 to 31,040 +/- 4,840 fmol/ml (p less than 0.003). Only 1.5% of pro ANF 1-98 and pro ANF 31-67 were cleared by the dialyzer membrane while 15% of ANF crossed the membrane. Thus, with hemodialysis the C-terminus decreases while the N-terminus and pro ANF 31-67 from the midportion of the N-terminus of the ANF prohormone increase in plasma which is partially explained by their respective abilities to cross the dialyzer membrane.

  10. Early trends in N-terminal pro-brain natriuretic peptide values after left ventricular assist device implantation for chronic heart failure.

    PubMed

    Hasin, Tal; Kushwaha, Sudhir S; Lesnick, Timothy G; Kremers, Walter; Boilson, Barry A; Schirger, John A; Clavell, Alfredo L; Rodeheffer, Richard J; Frantz, Robert P; Edwards, Brooks S; Pereira, Naveen L; Stulak, John M; Joyce, Lyle; Daly, Richard; Park, Soon J; Jaffe, Allan S

    2014-10-15

    Left ventricular assist devices (LVADs) acutely decrease left ventricular wall stress. Thus, early postoperative levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) should decrease. This study investigated postoperative changes in NT-proBNP levels, the parameters related to changes, and the possible association with complications by performing a retrospective analysis of changes in daily NT-proBNP (pg/ml) levels from admission to discharge both before and after LVAD implantation in a tertiary referral center. For 72 patients implanted with HeartMate II LVADs, baseline NT-proBNP levels were elevated at 3,943 ng/ml (interquartile range 1,956 to 12,964). Preoperative stabilization led to marked decreases in NT-proBNP. Levels peaked 3 days after surgery and subsequently decreased. Patients with complicated postoperative courses had higher early postoperative elevations. By discharge, NT-proBNP decreased markedly but was still 2.83 (1.60 to 5.76) times the age-based upper limit of normal. The 26% reduction in NT-proBNP between admission and discharge was due mostly to the preoperative reductions and not those induced by the LVAD itself. The decrease was not associated with decreases in LV volume. In conclusion, preoperative treatment reduces NT-proBNP values. The magnitude of early postoperative changes is related to the clinical course. Levels at discharge remain markedly elevated and similar to values after preoperative stabilization despite presumptive acute LV unloading.

  11. [Serum sclerostin levels and metabolic bone diseases].

    PubMed

    Yamauchi, Mika; Sugimoto, Toshitsugu

    2013-06-01

    Serum sclerostin levels are being investigated in various metabolic bone diseases. Since serum sclerostin levels are decreased in primary hyperparathyroidism and elevated in hypoparathyroidism, parathyroid hormone (PTH) is thought to be a regulatory factor for sclerostin. Serum sclerostin levels exhibit a significant positive correlation with bone mineral density. On the other hand, a couple of studies on postmenopausal women have shown that high serum sclerostin levels are a risk factor for fracture. Although glucocorticoid induced osteoporosis and diabetes are both diseases that reduce bone formation, serum sclerostin levels have been reported to be decreased in the former and elevated in the latter, suggesting differences in the effects of sclerostin in the two diseases. Serum sclerostin levels are correlated with renal function, and increase with reduction in renal function. Serum sclerostin level may be a new index of bone assessment that differs from bone mineral density and bone metabolic markers.

  12. SERUM PROTEIN PROFILES IN COCCIDIOIDOMYCOSIS

    PubMed Central

    Reed, William B.; Heiskell, Charles L.; Holeman, Charles W.; Carpenter, Charles

    1962-01-01

    Serum protein analysis is a valuable addition to the present methods for evaluating the status of the individual patient with coccidioidomycosis. The albumin protein and albumin glycoprotein decrease and gamma protein increases in relation to severity of infection. In 40 patients with coccidioidomycosis, changes in individual protein fractions could be significantly correlated with conventional laboratory tests, such as the complement fixation test, erythrocyte sedimentation rate and hematocrit. Changes in the alpha, glycoprotein concentration, the erythrocyte sedimentation rate and the hematocrit value appear to be related to the degree of inflammation, while the changes in the gamma protein and the beta, glycoprotein appear to be related to the specific antibody response. PMID:13973566

  13. Serum protein profiles in coccidioidomycosis.

    PubMed

    REED, W B; HEISKELL, C L; HOLEMAN, C W; CARPENTER, C

    1962-12-01

    Serum protein analysis is a valuable addition to the present methods for evaluating the status of the individual patient with coccidioidomycosis. The albumin protein and albumin glycoprotein decrease and gamma protein increases in relation to severity of infection. In 40 patients with coccidioidomycosis, changes in individual protein fractions could be significantly correlated with conventional laboratory tests, such as the complement fixation test, erythrocyte sedimentation rate and hematocrit. Changes in the alpha, glycoprotein concentration, the erythrocyte sedimentation rate and the hematocrit value appear to be related to the degree of inflammation, while the changes in the gamma protein and the beta, glycoprotein appear to be related to the specific antibody response.

  14. Reduction of blood serum cholesterol

    NASA Technical Reports Server (NTRS)

    Winitz, M. (Inventor)

    1974-01-01

    By feeding a human subject as the sole source of sustenance a defined diet wherein the carbohydrate consists substantially entirely of glucose, maltose or a polysaccharide of glucose, the blood serum cholesterol level of the human subject is substantially reduced. If 25 percent of the carbohydrate is subsequently supplied in the form of sucrose, an immediate increase from the reduced level is observed. The remainder of the defined diet normally includes a source of amino acids, such as protein or a protein hydrolysate, vitamins, minerals and a source of essential fatty acid.

  15. Neptunium uptake by serum transferrin.

    PubMed

    Llorens, Isabelle; Den Auwer, Christophe; Moisy, Philippe; Ansoborlo, Eric; Vidaud, Claude; Funke, Harld

    2005-04-01

    Although of major impact in terms of biological and environmental hazards, interactions of actinide cations with biological molecules are only partially understood. Human serum transferrin (Tf) is one of the major iron carriers in charge of iron regulation in the cell cycle and consequently contamination by actinide cations is a critical issue of nuclear toxicology. Combined X-ray absorption spectroscopy (XAS) and near infrared absorption spectrometry were used to characterize a new complex between Tf and Np (IV) with the synergistic nitrilotriacetic acid (NTA) anion. Description of the neptunium polyhedron within the iron coordination site is given.

  16. Serum enzyme activities after cardioversion

    PubMed Central

    Mandecki, Tadeusz; Giec, Leszek; Kargul, Włodzimierz

    1970-01-01

    Serum aspartate aminotransferase (SGOT), alanine aminotransferase (SGPT), creatinine phosphokinase (CPK), and butyric acid dehydrogenase (BDH) were determined in 94 patients before, 1½ hours, and 24 hours after cardioversion. An increase in SGOT and CPK activity was observed 24 hours after cardioversion in the group of patients treated with two or more DC shocks. The importance of this enzyme activity increase is discussed. It originates in the skeletal muscles and probably has no clinical significance, as no other signs of myocardial damage were observed simultaneously in a large group of patients. PMID:5470040

  17. International Reference Preparation of Rheumatoid Arthritis Serum

    PubMed Central

    Anderson, S. G.; Bentzon, M. W.; Houba, V.; Krag, P.

    1970-01-01

    The National Institute for Medical Research, London, England, was requested by the WHO Expert Committee on Biological Standardization to arrange a collaborative study of the serum pool they had obtained, to determine its suitability to serve as an international reference preparation of rheumatoid arthritis serum. A batch of this serum was assayed by 11 laboratories in 7 countries against 30 test preparations. On the basis of the results obtained, the serum has been established as the International Reference Preparation of Rheumatoid Arthritis Serum and the International Unit of Rheumatoid Arthritis Serum has been defined as the activity contained in 0.171 mg of the international reference preparation. A description is also given of the British reference preparation of rabbit antibody to sheep red blood cells (amboceptor) and this material was also tested in the collaborative study. PMID:5310143

  18. Effect of Pregnancy Serum on Experimental Inflammation

    PubMed Central

    Persellin, R. H.; Vance, S. E.; Peery, A.

    1974-01-01

    Experimental inflammation induced in the rat by injection of carrageenin was suppressed by prior administration of pooled serum obtained from pregnant human females. Inflammatory oedema in the rat hind paw measured by a plethysmograph was inhibited 81% by 10 ml of pregnancy serum pool and the effect was dose related. Non-pregnant female serum was inhibitory to a lesser degree and no anti-inflammatory action was detected using cord serum. Although adrenal corticosteroid hormones could modify this inflammatory model, their presence in the serum pools could not account for the effects observed. Since carrageenin is sequestered within phagolysosomes and provokes release of their inflammation-inducing contents, it is suggested that the protective effect of pregnancy serum on carrageenin inflammation is mediated via lysosomal stabilization. PMID:4835795

  19. Association of Nicotinamide Phosphoribosyltransferase (NAMPT) Gene Polymorphisms and of Serum NAMPT Levels with Dilated Cardiomyopathy in a Chinese Population

    PubMed Central

    Dou, Qingyu; Peng, Ying; Zhou, Bin; Zhang, Kui; Lin, Jing; Dai, Xiaohui; Zhang, Lin; Rao, Li

    2015-01-01

    serum NAMPT levels. Spearman correlation test revealed that the NAMPT level was positively associated with brain natriuretic peptide (r = 0.56, p = 0.001), left ventricular end-diastolic diameter (r = 0.293, p = 0.011) and left ventricular end-diastolic volume (r = 0.294, p = 0.011). Our study suggested that NAMPT may play an important role in the development of DCM. PMID:26389889

  20. Kinetic analysis of internalization, recycling and redistribution of atrial natriuretic factor-receptor complex in cultured vascular smooth-muscle cells. Ligand-dependent receptor down-regulation.

    PubMed Central

    Pandey, K N

    1992-01-01

    The kinetics of internalization, sequestration and metabolic degradation of atrial natriuretic factor (ANF)-receptor complex were studied in rat thoracic aortic smooth-muscle (RTASM) cells. These parameters were directly determined by measuring 125I-ANF binding to total, intracellular and cell-surface receptors. Pretreatment of cells with the lysosomotropic agent chloroquine and the energy depleter dinitrophenol led to an increase in the intracellular 125I-ANF radioactivity. After 60 min incubation at 37 degrees C, cell-associated 125I-ANF radioactivity fell rapidly in chloroquine-treated cells (> 85%) compared with the controls (< 45%). 125I-ANF radioactivity increased to a peak of 65% of the initial level within 15 min in chloroquine-treated cells compared with only 22% in the control cells. During the initial incubation period at 37 degrees C, chloroquine inhibited the release of both intact and degraded 125I-ANF in a time-dependent manner. However, at later incubation times, the effect of chloroquine was diminished and release of both degraded and intact ligand was resumed. Extracellular unlabelled ANF did not affect the release of degraded 125I-ANF but it accelerated the release of intact ANF by a retroendocytotic mechanism. After the endocytosis, about 30-40% of ANF receptors were restored to the cell surface from the internalized pool of receptors. The restoration was blocked by chloroquine or dinitrophenol but not by cycloheximide. Exposure of RTASM cells to unlabelled ANF resulted in a time- and concentration-dependent loss of ANF receptors. Unlabelled ANF (10 nM) induced a loss of more than 52% of 125I-ANF binding, and a complete loss occurred at micromolar concentrations. It is inferred that ANF-induced down-regulation of its receptor resulted primarily from an increased rate in internalization and metabolic degradation of ligand-receptor complex by receptor-mediated endocytotic mechanisms. PMID:1445281

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

    PubMed

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

    2016-06-01

    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 cm(2) ·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.

  2. 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

  3. Effects of immobilizations stress with or without water immersion on the expression of atrial natriuretic peptide in the hearts of two rat strains.

    PubMed

    Slavikova, Jana; Mistrova, Eliska; Klenerova, Vera; Kruzliak, Peter; Caprnda, Martin; Hynie, Sixtus; Sida, Pavel; Dvorakova, Magdalena Chottova

    2016-01-01

    Atrial natriuretic peptide (ANP) is produced and released by mammalian cardiomyocytes and induces natriuresis, diuresis, and lowering of blood pressure. The present study examined localization of ANP and a possible role of the hypothalamic-pituitary-adrenal axis (HPA) activity on the expression of proANP gene in the heart. The Sprague Dawley (SD) and Lewis (LE) rat strains were used. The animals were exposed to the two types of stress: immobilization and immobilization combined with water immersion for 1 hour. Localization of ANP was detected by immunohistochemistry and expression of the proANP mRNA by real-time qPCR in all heart compartments of control and stressed animals after 1 and 3 hours after stress termination (IS1, IS3, ICS1, and ICS3). Relatively high density of ANP-immunoreactivity was observed in both atria of both rat strains. In control rats of both strains, the expression of the proANP mRNA was higher in the atria than in ventricles. In SD rats with the intact HPA axis, an upregulation of ANP gene expression was observed in the right atrium after IS1, in both atria and the left ventricle after IS3 and in the left atrium and the left ventricle after ICS3. In LE rats with a blunted reactivity of the HPA axis, no increase or even a downregulation of the gene expression was observed. Thus, acute stress-induced increase in the expression of the proANP gene is related to the activity of the HPA axis. It may have relevance to ANP-induced protection of the heart.

  4. Effects of immobilizations stress with or without water immersion on the expression of atrial natriuretic peptide in the hearts of two rat strains

    PubMed Central

    Slavikova, Jana; Mistrova, Eliska; Klenerova, Vera; Kruzliak, Peter; Caprnda, Martin; Hynie, Sixtus; Sida, Pavel; Dvorakova, Magdalena Chottova

    2016-01-01

    Atrial natriuretic peptide (ANP) is produced and released by mammalian cardiomyocytes and induces natriuresis, diuresis, and lowering of blood pressure. The present study examined localization of ANP and a possible role of the hypothalamic-pituitary-adrenal axis (HPA) activity on the expression of proANP gene in the heart. The Sprague Dawley (SD) and Lewis (LE) rat strains were used. The animals were exposed to the two types of stress: immobilization and immobilization combined with water immersion for 1 hour. Localization of ANP was detected by immunohistochemistry and expression of the proANP mRNA by real-time qPCR in all heart compartments of control and stressed animals after 1 and 3 hours after stress termination (IS1, IS3, ICS1, and ICS3). Relatively high density of ANP-immunoreactivity was observed in both atria of both rat strains. In control rats of both strains, the expression of the proANP mRNA was higher in the atria than in ventricles. In SD rats with the intact HPA axis, an upregulation of ANP gene expression was observed in the right atrium after IS1, in both atria and the left ventricle after IS3 and in the left atrium and the left ventricle after ICS3. In LE rats with a blunted reactivity of the HPA axis, no increase or even a downregulation of the gene expression was observed. Thus, acute stress-induced increase in the expression of the proANP gene is related to the activity of the HPA axis. It may have relevance to ANP-induced protection of the heart. PMID:27508036

  5. Recombinant Atrial Natriuretic Peptide Prevents Aberrant Ca2+ Leakage through the Ryanodine Receptor by Suppressing Mitochondrial Reactive Oxygen Species Production Induced by Isoproterenol in Failing Cardiomyocytes

    PubMed Central

    Susa, Takehisa; Nanno, Takuma; Ishiguchi, Hironori; Myoren, Takeki; Nishimura, Shigehiko; Kato, Takayoshi; Hino, Akihiro; Oda, Tetsuro; Okuda, Shinichi; Yamamoto, Takeshi; Yano, Masafumi

    2016-01-01

    Catecholamines induce intracellular reactive oxygen species (ROS), thus enhancing diastolic Ca2+ leakage through the ryanodine receptor during heart failure (HF). However, little is known regarding the effect of atrial natriuretic peptide (ANP) on ROS generation and Ca2+ handling in failing cardiomyocytes. The aim of the present study was to clarify the mechanism by which an exogenous ANP exerts cardioprotective effects during HF. Cardiomyocytes were isolated from the left ventricles of a canine tachycardia-induced HF model and sham-operated vehicle controls. The degree of mitochondrial oxidized DNA was evaluated by double immunohistochemical (IHC) staining using an anti-VDAC antibody for the mitochondria and an anti-8-hydroxy-2′-deoxyguanosine antibody for oxidized DNA. The effect of ANP on ROS was investigated using 2,7-dichlorofluorescin diacetate, diastolic Ca2+ sparks assessed by confocal microscopy using Fluo 4-AM, and the survival rate of myocytes after 48 h. The double IHC study revealed that isoproterenol (ISO) markedly increased oxidized DNA in the mitochondria in HF and that the ISO-induced DNA damage was markedly inhibited by the co-presence of ANP. ROS production and Ca2+ spark frequency (CaSF) were increased in HF compared to normal controls, and were further increased in the presence of ISO. Notably, ANP significantly suppressed both ISO-induced ROS and CaSF without changing sarcoplasmic reticulum Ca2+ content in HF (p<0.01, respectively). The survival rate after 48 h in HF was significantly decreased in the presence of ISO compared with baseline (p<0.01), whereas it was significantly improved by the co-presence of ANP (p<0.01). Together, our results suggest that ANP strongly suppresses ISO-induced mitochondrial ROS generation, which might correct aberrant diastolic Ca2+ sparks, eventually contributing to the improvement of cardiomyocyte survival in HF. PMID:27657534

  6. Changes in cardiac aldosterone and its synthase in rats with chronic heart failure: an intervention study of long-term treatment with recombinant human brain natriuretic peptide.

    PubMed

    Zhu, X Q; Hong, H S; Lin, X H; Chen, L L; Li, Y H

    2014-08-01

    The physiological mechanisms involved in isoproterenol (ISO)-induced chronic heart failure (CHF) are not fully understood. In this study, we investigated local changes in cardiac aldosterone and its synthase in rats with ISO-induced CHF, and evaluated the effects of treatment with recombinant human brain natriuretic peptide (rhBNP). Sprague-Dawley rats were divided into 4 different groups. Fifty rats received subcutaneous ISO injections to induce CHF and the control group (n=10) received equal volumes of saline. After establishing the rat model, 9 CHF rats received no further treatment, rats in the low-dose group (n=8) received 22.5 μg/kg rhBNP and those in the high-dose group (n=8) received 45 μg/kg rhBNP daily for 1 month. Cardiac function was assessed by echocardiographic and hemodynamic analysis. Collagen volume fraction (CVF) was determined. Plasma and myocardial aldosterone concentrations were determined using radioimmunoassay. Myocardial aldosterone synthase (CYP11B2) was detected by quantitative real-time PCR. Cardiac function was significantly lower in the CHF group than in the control group (P<0.01), whereas CVF, plasma and myocardial aldosterone, and CYP11B2 transcription were significantly higher than in the control group (P<0.05). Low and high doses of rhBNP significantly improved hemodynamics (P<0.01) and cardiac function (P<0.05) and reduced CVF, plasma and myocardial aldosterone, and CYP11B2 transcription (P<0.05). There were no significant differences between the rhBNP dose groups (P>0.05). Elevated cardiac aldosterone and upregulation of aldosterone synthase expression were detected in rats with ISO-induced CHF. Administration of rhBNP improved hemodynamics and ventricular remodeling and reduced myocardial fibrosis, possibly by downregulating CYP11B2 transcription and reducing myocardial aldosterone synthesis.

  7. Sensitive immunosensor for N-terminal pro-brain natriuretic peptide based on N-(aminobutyl)-N-(ethylisoluminol)-functionalized gold nanodots/multiwalled carbon nanotube electrochemiluminescence nanointerface.

    PubMed

    Zhang, Hongli; Han, Zhili; Wang, Xu; Li, Fang; Cui, Hua; Yang, Di; Bian, Zhiping

    2015-04-15

    A novel electrochemiluminescence (ECL) immunosensor was developed for the determination of N-terminal pro-brain natriuretic peptide (NT-proBNP) by using N-(aminobutyl)-N-(ethylisoluminol) (ABEI)-functionalized gold nanodots/chitosan/multiwalled carbon nanotubes (ABEI/GNDs/chitosan/COOH-MWCNTs) hybrid as nanointerface. First, ABEI/GNDs/chitosan/COOH-MWCNTs hybrid nanomaterials were grafted onto the surface of ITO electrode via the film-forming property of hybrid nanomaterials. The anti-NT-proBNP antibody was connected to the surface of modified electrode by virtue of amide reaction via glutaraldehyde. The obtained sensing platform showed strong and stable ECL signal. When NT-proBNP was captured by its antibody immobilized on the sensing platform via immunoreaction, the ECL intensity decreased. Direct ECL signal changes were used for the determination of NT-proBNP. The present ECL immunosensor demonstrated a quite wide linear range of 0.01-100 pg/mL. The achieved low detection limit of 3.86 fg/mL was about 3 orders of magnitude lower than that obtained with electrochemistry method reported previously. Because of the simple and fast analysis, high sensitivity and selectivity, and stable and reliable response, the present immunosensor has been successfully applied to quantify NT-proBNP in practical plasma samples. The success of the sensor in this work also confirms that ABEI/GNDs/chitosan/COOH-MWCNTs hybrid is an ideal nanointerface to fabricate a sensing platform. Furthermore, the proposed strategy could be applied in the detection of other clinically important biomarkers.

  8. Genetically Alt