natriuretic-peptide--brain and Body-Weight

Glucagon-like peptide 1 receptor agonists (GLP-1RA) decrease the risk of major adverse cardiovascular events (MACE). However, their influence on the risk of heart failure (HHF) hospitalization is marginal, which is unexpected given their benefits on cardiometabolic risk, especially on bodyweight reduction. This meta-analysis aimed to map the effects of GLP-1RA on N-terminal pro-BNP.. We retrieved from a Medline and Embase all randomized trials comparing GLP-1RA with placebo, reporting NT-proBNP concentrations. The primary outcome was the change in N-terminal pro-BNP values from baseline to end-of-treatment with GLP-1RA versus placebo (reported as standard deviations, SD). We included nine trials (543 patients in active treatment and 536 in placebo). We observed significantly greater reductions in N-terminal pro-BNP with GLP-1RA versus placebo (-0.14 SD; 95% CI -0.27; -0.01; p = 0.03). Upon meta-regression, no modifying effect of age, HbA1c, and body mass index were observed, nor was any meta-correlation between the change in NT-proBNP and the change in HbA1c or body weight.. GLP-1RA can significantly decrease N-terminal pro-BNP. This effect was independent of baseline age, body weight, and metabolic control.

Topics: Body Weight; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Natriuretic Peptide, Brain; Peptide Fragments

Acute decompensated heart failure (ADHF), with an incidence of 1-2%, is a clinical syndrome with significant morbidity and mortality despite therapeutic advancements and ongoing clinical trials. A recent therapeutic approach to patients with ADHF includes combination therapy with hypertonic saline solution (HSS) and furosemide, based on the hypothesis that resistance to loop diuretics occurs because of achievement of plateau in water and sodium excretion in patients receiving long-term loop diuretic therapy.. Our aim was to conduct a meta-analysis to evaluate the efficiency of combination HSS plus furosemide therapy in patients with ADHF in terms of mortality, readmissions, length of hospital stay, kidney function, urine output, body weight, and B-type natriuretic peptide (BNP).. A total of 14 studies-four observational and ten randomized studies (total 3398 patients)-were included in the meta-analysis.. Our results demonstrate the superiority of combination HSS plus furosemide therapy over furosemide alone in terms of kidney function preservation (mean creatinine difference - 0.33 mg/dL; P < 0.00001), improved diuresis (mean difference [MD] 581.94 mL/24 h; P < 0.00001) and natriuresis (MD 57.19; P < 0.00001), weight loss (MD 0.99 kg; P < 0.00001), duration of hospital stay (MD - 2.72 days; P < 0.00001), readmissions (relative risk 0.63; P = 0.01), and mortality (relative risk 0.55; P < 0.00001). However, no difference in BNP levels was detected (MD 19.88 pg/mL; P = 0.50).. Despite the heterogeneity and possible risk of bias among the studies, results appear promising on multiple aspects. A clear need exists for future randomized controlled trials investigating the role of combination HSS plus furosemide therapy to clarify these effects and their possible mechanisms.

Topics: Body Weight; Diuresis; Diuretics; Drug Therapy, Combination; Furosemide; Heart Failure; Humans; Kidney Function Tests; Length of Stay; Natriuretic Peptide, Brain; Observational Studies as Topic; Patient Readmission; Randomized Controlled Trials as Topic; Saline Solution, Hypertonic; Weight Loss

Estimating the euvolemia and dry weight of hemodialysis patients still represents a challenge for the nephrologist, since both dehydration and hyperhydration are associated with intradialytic events and cardiovascular complications in the short and long term. Despite the need for a precise and objective definition of the dry weight for the individual patient on dialysis, this is usually determined on a clinical basis. To obtain greater sensitivity the dosage of natriuretic peptides, Bioelectrical Impedance Analysis (BIA) and, more recently, Lung Ultra-Sound (LUS) can all be used. The BIA allows to estimate the subject's body composition and, in particular, the distribution of body fluids. The presence of hyperhydration, as determined through the BIA, is predictive of an increased mortality in numerous observational studies. In recent years, pulmonary ultrasound has taken on an increasingly important role not only within the cardiology and intensive care units, but also in a nephrology setting, especially in dialysis. The purpose of this article is to analyze the advantages and limitations of the methods that can be used to assess the dry weight of patients undergoing hemodialysis treatment.

Topics: Blood Pressure; Body Composition; Body Water; Body Weight; Electric Impedance; Humans; Lung; Natriuretic Peptide, Brain; Organism Hydration Status; Peptide Fragments; Renal Dialysis; Ultrasonography

The assessment of extracellular fluid volume (ECV) and fluid status is both important and challenging in hemodialysis patients. Extracellular fluid is distributed in two major sub-compartments: interstitial fluid and plasma. A variety of methods are used to assess the ECV, with tracer dilution techniques considered gold standard. However, ECV defined as the distribution space of bromide, sodium, chloride, and ferrocyanide appears to be larger than the distribution volume of inulin and sucrose, suggesting a partial distribution into the intracellular volume. Relative blood volume monitoring, measurement of inferior vena cava diameter by ultrasound and biochemical markers are indirect methods, which do not reflect the ECV and fluid status accurately. Bioimpedance spectroscopy (BIS) techniques enable assessment of ECV and intracellular volume. Currently, BIS appears to be the most practical method for assessing ECV volume and fluid status in dialysis patients.

Topics: Blood Volume; Body Fluids; Body Weight; Electric Impedance; Extracellular Fluid; Humans; Kidney Failure, Chronic; Models, Biological; Natriuretic Peptide, Brain; Plasma Volume; Potassium; Renal Dialysis; Sodium; Spectrum Analysis; Ultrasonography; Vena Cava, Inferior; Water-Electrolyte Imbalance

This article addresses a question that the authors consider to be somewhat rhetorical: are hemodynamic parameters predictors of mortality? It reviews the specific hemodynamic abnormalities and pathophysiologic consequences distinctive to the patient who has decompensation and addresses the data that implicate abnormal hemodynamics as a treatment target associated with increased mortality. The focus is on patients who have decompensated heart failure, defined as left ventricular systolic dysfunction and an acute, subacute, or gradual worsening of symptoms while receiving optimal medical therapy.

Topics: Angiotensin-Converting Enzyme Inhibitors; Body Weight; Cardiac Output; Heart Failure; Hemodynamics; Hospitalization; Humans; Natriuretic Peptide, Brain; Pulmonary Wedge Pressure; Sensitivity and Specificity; Ventricular Function, Left; Ventricular Pressure

A review is given on methods that can be used for the assessment of dry body weight in peritoneal dialysis patients. Besides clinical examination, the use of natriuretic hormone concentrations in plasma, and the value of multifrequency bio-impedance analysis is discussed. Ultrafiltration targets as formulated in various guidelines are reviewed. Finally, it is concluded that the ultrafiltration target is the amount required to keep patients euvolemic with an exposure to glucose that is as low as possible.

Topics: Body Weight; Electric Impedance; Glucose; Humans; Natriuretic Peptide, Brain; Peritoneal Dialysis; Ultrafiltration

Topics: Albuminuria; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Body Weight; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Neuropathies; Diabetic Retinopathy; Diet; Drug Therapy, Combination; Dyslipidemias; Endothelium, Vascular; Glomerular Filtration Rate; Health Behavior; Humans; Hypertension; Insulin Resistance; Kidney; Life Style; Natriuretic Peptide, Brain; Peptide Fragments; Risk Assessment; Risk Factors; Smoking; Smoking Cessation; Survival Analysis; Treatment Outcome; Vitamins

Natriuretic peptides are involved in the regulation of volume homeostasis. Their levels generally are increased in the setting of volume expansion and act on multiple effector systems to cause vasodilation and natriuresis in an effort to return volume status back to normal. In patients with end-stage renal disease, the natriuretic capabilities of these peptides are limited. However, there has been much interest in the potential applicability of measurement of these peptides as a surrogate marker of volume status and in the determination of dry weight. Furthermore, atrial natriuretic peptide and brain natriuretic peptide can serve as markers of left ventricular dysfunction and may have utility in determining cardiac prognosis in patients on long-term dialysis therapy.

Topics: Animals; Atrial Natriuretic Factor; Biomarkers; Blood Volume; Body Weight; Cohort Studies; Heart Failure; Humans; Kidney; Kidney Failure, Chronic; Natriuresis; Natriuretic Peptide, Brain; Natriuretic Peptides; Peritoneal Dialysis; Prognosis; Rats; Receptors, Neuropeptide; Ventricular Dysfunction, Left; Water-Electrolyte Balance

B-type natriuretic peptide (BNP) is a cardiac neurohormone released as preproBNP and then enzymatically cleaved to N-terminal-proBNP and BNP upon ventricular myocyte stretch. Blood measurements of BNP have been used to identify patients with heart failure. Currently, BNP assay is used as a diagnostic and prognostic aid in congestive heart failure. In general, a BNP level <100 pg/mL excludes acutely decompensated heart failure. This article sorts out the literature concerning the practical use of BNP in a variety of clinical scenarios.

Topics: Acute Disease; Adult; Age Factors; Aged; Algorithms; Ambulatory Care; Body Weight; Decision Trees; Drug Monitoring; Dyspnea; Female; Heart Failure; Humans; Male; Metabolic Clearance Rate; Middle Aged; Natriuretic Peptide, Brain; Practice Guidelines as Topic; Prognosis; Reference Values; Sensitivity and Specificity; Severity of Illness Index; Sex Characteristics; Treatment Outcome

Fluid overload is associated with adverse outcomes in hemodialysis (HD) patients. The precise assessment of hydration status in HD patients remains a major challenge for nephrologists. Our study aimed to explore whether combining two bedside methods, lung ultrasonography (LUS) and bioimpedance, may provide complementary information to guide treatment in specific HD patients.. In total, 250 HD patients from two dialysis units were included in this randomized clinical trial. Patients were randomized 1:1 to have a dry weight assessment based on clinical (control) or LUS with bioimpedance in case of clinical hypovolemia (active)-guided protocol. The primary outcome was to assess the difference between the two groups on a composite of all-cause mortality and first cardiovascular event (CVE)-including death, stroke, and myocardial infarction.. During a mean follow-up period was 21.3 ± 5.6 months, there were 54 (21.6%) composite events in the entire population. There was a nonsignificant 9% increase in the risk of this outcome in the active arm (HR = 1.09, 95% CI 0.64-1.86, p = 0.75). Similarly, there were no differences between the two groups when analyzing separately the all-cause mortality and CVE outcomes. However, patients in the active arm had a 19% lower relative risk of pre-dialytic dyspnea (rate ratio-0.81, 95% CI 0.68-0.96), but a 26% higher relative risk of intradialytic cramps (rate ratio-1.26, 95% CI 1.16-1.37).. This study shows that a LUS-bioimpedance-guided dry weight adjustment protocol, as compared to clinical evaluation, does not reduce all-cause mortality and/or CVE in HD patients. A fluid management protocol based on bioimpedance with LUS on indication might be a better strategy.

Topics: Adult; Aged; Body Composition; Body Water; Body Weight; Cause of Death; Electric Impedance; Female; Follow-Up Studies; Hemodialysis Solutions; Hospitalization; Humans; Hypotension; Kidney Failure, Chronic; Lung; Male; Middle Aged; Monitoring, Physiologic; Muscle Cramp; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Pulse Wave Analysis; Renal Dialysis; Risk Assessment; Stroke; Troponin T; Ultrasonography; Vascular Stiffness

Heart failure is a common cause of hospitalization and can be divided into types with preserved and reduced ejection fraction (HFpEF and HFrEF, respectively). In this subanalysis of the HABIT (Heart Failure Assessment With BNP in the Home) trial, we examined the differences between home B-type natriuretic peptide (BNP) testing and weight monitoring in patients with HFpEF and with HFrEF before decompensation.. This was a retrospective review of patients with HFpEF and HFrEF from the HABIT trial. The HFpEF patients compared with HFrEF patients were older and more obese and had lower baseline BNP values. Intra-individual BNP dispersion (spread of distribution over time) was greater in HFpEF than in HFrEF owing to rapid fluctuations (within 3 days). Slowly varying changes in BNP (estimated by a moving average) were equally predictive of ADHF risk in both HFpEF and HFrEF. However, in HFpEF, a rapid rise in BNP >200 pg/mL within 3 days was associated with an increased risk of acute decompensated heart failure (ADHF; hazard ratio 4.0), whereas a similar association was not observed in HFrEF. Weight gain ≥5 lb in 3 days had a high specificity but low sensitivity for ADHF in both HFpEF and HFrEF, whereas a lower threshold of ≥2 lb weight gain over 3 days in patients with HFpEF (but not HFrEF) was a moderately sensitive cutoff associated with decompensation (60% sensitivity).. Patients with HFpEF and HFrEF have variations in their BNP and weight before decompensation. The rapid time scale behaves differently between the groups. In those with HFpEF, a 3-day period characterized by ≥2 lb weight gain and/or >200 pg/mL BNP rise was significantly associated with decompensation. Future prospective studies investigating different weight and BNP cutoffs for home monitoring of HFpEF and HFrEF patients should be performed to fully learn the value of BNP changes before clinical deompensation.

Topics: Aged; Biomarkers; Body Weight; Double-Blind Method; Female; Heart Failure; Home Care Services; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Prospective Studies; Retrospective Studies; Stroke Volume; Weight Gain

To evaluate the effects of canrenone compared to placebo on blood pressure control, some non-conventional biomarkers in cardiovascular stratification, and on metalloproteinases in patients affected by metabolic syndrome.. A total of 156 Caucasian patients were treated with placebo or canrenone, 50 mg once a day, for 3 months and then 50 mg twice a day, till the end of the study. We evaluated: systolic (SBP) and diastolic blood pressure (DBP), body weight, body mass index (BMI), fasting plasma glucose (FPG), lipid profile, plasma aldosterone, creatinine, potassium, brain natriuretic peptide (BNP), metalloproteinases 2 and 9 (MMP-2 and -9), lipoprotein (a) (Lp(a)), and serum myeloperoxidase (MPO).. We observed a significant decrease of SBP and DBP in the canrenone group compared to baseline. Canrenone gave a significant decrease of MMP-2 and -9, Lp(a), and MPO compared to baseline, not observed with placebo. Plasma aldosterone, but not BNP, decreased with canrenone, both compared to baseline and to placebo.. Canrenone seems to be effective in reducing blood pressure in patients with metabolic syndrome. Moreover, canrenone seems also to improve MPO, Lp(a), and metalloproteinases in these patients.

Topics: Aged; Aldosterone; Biomarkers; Blood Glucose; Blood Pressure; Body Mass Index; Body Weight; Canrenone; Creatine; Double-Blind Method; Fasting; Female; Humans; Inflammation; Lipids; Lipoproteins; Male; Metabolic Syndrome; Metalloproteases; Middle Aged; Natriuretic Peptide, Brain; Peroxidase; Potassium; White People

GLP-1 receptor (GLP-1R) agonists induce natriuresis and reduce blood pressure (BP) through incompletely understood mechanisms. We examined the effects of acute and 21-day administration of liraglutide on plasma atrial natriuretic peptide (ANP), urinary sodium excretion, office and 24-h BP, and heart rate (HR).. Liraglutide or placebo was administered for 3 weeks to hypertensive subjects with type 2 diabetes in a double-blinded, randomized, placebo-controlled crossover clinical trial in the ambulatory setting. End points included within-subject change from baseline in plasma ANP, Nt-proBNP, office BP, and HR at baseline and over 4 h following a single dose of liraglutide (0.6 mg) and after 21 days of liraglutide (titrated to 1.8 mg) versus placebo administration. Simultaneous 24-h ambulatory BP and HR monitoring and 24-h urine collections were measured at baseline and following 21 days of treatment.. Plasma ANP levels did not change significantly after acute (+16.72 pg/mL, P = 0.24, 95% CI [-12.1, +45.5] at 2 h) or chronic (-17.42 pg/mL, 95% CI [-36.0, +1.21] at 2 h) liraglutide administration. Liraglutide significantly increased 24-h and nighttime urinary sodium excretion; however, 24-h systolic BP was not significantly different. Small but significant increases in 24-h and nighttime diastolic BP and HR were observed with liraglutide. Body weight, HbA1c, and cholesterol were lower, and office-measured HR was transiently increased (for up to 4 h) with liraglutide administration.. Sustained liraglutide administration for 3 weeks increases urinary sodium excretion independent of changes in ANP or BP in overweight and obese hypertensive patients with type 2 diabetes.

Topics: Adult; Aged; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Endpoint Determination; Female; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Heart Rate; Humans; Hypertension; Liraglutide; Male; Middle Aged; Natriuresis; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Receptors, Glucagon; Sodium

Matrix metalloproteinases (MMPs) are a family of enzymes important for the resorption of extracellular matrices, control of vascular remodeling and repair. Increased activity of MMP2 has been demonstrated in heart failure, and in acutely decompensated heart failure (ADHF) a decrease in circulating MMPs has been demonstrated along with successful treatment.. Our aim was to test the influence of spironolactone in MMP2 levels.. Secondary analysis of a prospective, interventional study including 100 patients with ADHF. Fifty patients were non-randomly assigned to spironolactone (100 mg/day) plus standard ADHF therapy (spironolactone group) or standard ADHF therapy alone (control group).. Spironolactone group patients were younger and had lower creatinine and urea levels (all p < 0.05). Baseline MMP2, NT-pro BNP and weight did not differ between spironolactone and control groups. A trend towards a more pronounced decrease in MMP2 from baseline to day 3 was observed in the spironolactone group (-21 [-50 to 19] vs 1.5 [-26 to 38] ng/mL, p = 0.06). NT-pro BNP and weight also had a greater decrease in the spironolactone group. The proportion of patients with a decrease in MMP2 levels from baseline to day 3 was also likely to be greater in the spironolactone group (50% vs 66.7%), but without statistical significance. Correlations between MMP2, NT-pro BNP and weight variation were not statistically significant.. MMP2 levels are increased in ADHF. Patients treated with spironolactone may have a greater reduction in MMP2 levels.

Topics: Acute Disease; Aged; Aged, 80 and over; Body Weight; Creatinine; Diuretics; Female; Heart Failure; Humans; Male; Matrix Metalloproteinase 2; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Spironolactone; Urea

There are limited data comparing ultrafiltration with standard medical therapy as first-line treatment in patients with severe congestive heart failure (HF). We compared ultrafiltration and conventional therapy in patients hospitalized for HF and overt fluid overload.. Fifty-six patients with congestive HF were randomized to receive standard medical therapy (control group; n = 29) or ultrafiltration (ultrafiltration group; n = 27). The primary end point of the study was rehospitalizations for congestive HF during a 1-year follow-up. Despite similar body weight reduction at hospital discharge in the 2 groups (7.5 ± 5.5 and 7.9 ± 9.0 kg, respectively; P = .75), a lower incidence of rehospitalizations for HF was observed in the ultrafiltration-treated patients during the following year (hazard ratio 0.14, 95% confidence interval 0.04-0.48; P = .002). Ultrafiltration-induced benefit was associated with a more stable renal function, unchanged furosemide dose, and lower B-type natriuretic peptide levels. At 1 year, 7 deaths (30%) occurred in the ultrafiltration group and 11 (44%) in the control group (P = .33).. In HF patients with severe fluid overload, first-line treatment with ultrafiltration is associated with a prolonged clinical stabilization and a greater freedom from rehospitalization for congestive HF.

Topics: Aged; Aged, 80 and over; Body Weight; Cardiovascular Agents; Confidence Intervals; Diuretics; Dose-Response Relationship, Drug; Female; Furosemide; Heart Failure; Humans; Kidney Function Tests; Male; Monitoring, Physiologic; Natriuretic Peptide, Brain; Patient Readmission; Proportional Hazards Models; Severity of Illness Index; Treatment Outcome; Ultrafiltration

Although the cardiac biomarker B-type natriuretic peptide (BNP) is strongly related to mortality in end-stage renal disease (ESRD), whether it is a predictor of weight change or blood pressure (BP) response upon probing dry weight among hypertensive hemodialysis patients remains unknown. The purpose of this study was to examine among people with hypertension on hemodialysis whether BNP is a biomarker of excess volume.. Hypertensive hemodialysis patients (n = 150) were randomized to a control group (n = 50) or an ultrafiltration group (n = 100) and followed up for 30 dialysis treatments. After a baseline run-in of six treatments, those assigned to the ultrafiltration group had dry weight probed over 8 weeks. Forty-four-hour interdialytic ambulatory BP and predialysis BNP were measured at the end of run-in period, at 4 weeks and at 8 weeks.. The median BNP concentration was 93 pg/mL (interquartile range 31-257 pg/mL). The magnitude of decline in the BNP depended on the baseline concentration of BNP, but did not require probing dry weight or weight loss. No relationship existed between decline in postdialysis weight upon probing dry weight and baseline BNP. Furthermore, reduction in the BNP was not required for decline in postdialysis weight. Predialysis log BNP modestly predicted ambulatory systolic and pulse pressure independently of other risk factors. No relationship was found between decline in BP upon probing dry weight and baseline BNP. Upon probing dry weight, reduction in BNP was not required for decline in systolic ambulatory BP.. Taken together, these data suggest that among hypertensive patients on hemodialysis BNP is not a volume marker.

Topics: Adolescent; Adult; Biomarkers; Blood Pressure Monitoring, Ambulatory; Blood Volume; Body Weight; Case-Control Studies; Cohort Studies; Female; Follow-Up Studies; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Renal Dialysis; Young Adult

In spite of appropriate pharmacologic therapy, many hypertensive patients develop an abnormal left ventricular relaxation with preserved systolic function. This cardiac dysfunction increases the risk of cardiovascular complications. The authors assessed the therapeutic effects of an intervention with exercise training and weight reduction in patients with pharmacologically well-treated hypertension who had abnormal left ventricular relaxation with normal systolic function. Eighty-eight (44%) of 202 medically treated hypertensive patients had abnormal ventricular relaxation with normal ejection fraction. These patients were randomized to either a 6-month intervention program (cycle ergometer training twice a day for 5 days a week and a hypocaloric diet) or a control program (unchanged pharmacologic therapy without exercise and diet. Body weight, blood pressure, New York Heart Association class, glomerular filtration rate, and exercise capacity and workload were measured. Cardiac function was assessed by measuring N-terminal pro-B-type natriuretic peptide values, the electrocardiographic QT dispersion interval, and echocardiography (left atrial size, Doppler-derived E/A ratio, and mitral deceleration time). Physical exercise with weight reduction reduced blood pressure, decreased cardiovascular risks, and improved abnormal left ventricular relaxation. Measuring left atrial size is the best method for assessing changes in left ventricular relaxation with preserved systolic function.

Topics: Antihypertensive Agents; Blood Pressure; Body Weight; Diet, Reducing; Electrocardiography; Exercise; Exercise Therapy; Exercise Tolerance; Female; Glomerular Filtration Rate; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Ventricular Function, Left; Weight Loss

The aim of the present study was to interpret B-type natriuretic peptide (BNP) level in outpatients with stable chronic heart failure (CHF); it is important to clarify whether the change in BNP represents disease progression or a range of biological variation.. To compare biological variation in BNP and biological variation in factors of the renin-angiotensin-aldosterone system (RAS) in stable CHF patients with dilated cardiomyopathy (DCM), the BNP plasma levels and RAS factors were measured in 115 stable outpatients with DCM. According to stepwise multivariate analysis, plasma BNP at baseline (P=0.005), presence of atrial fibrillation (P=0.015), and a high biological variation in plasma renin concentration (PRC; P=0.002) were significant independent dominant factors related to a high biological variation in BNP. Although there was no change in body weight or blood pressure during the 2-month study period, the % change in hematocrit was negatively correlated with % change in BNP (r=-0.327, P=0.0008), and positively correlated with % change in PRC (r=0.671, P=0.001).. There was a significant relationship between biological variation in BNP and biological variation in PRC, suggesting that the physiological interaction between the natriuretic peptide system and RAS may contribute to the biological variation in plasma BNP in stable outpatients with DCM.

Topics: Aged; Blood Pressure; Body Weight; Cardiomyopathy, Dilated; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Observer Variation; Outpatients; Prospective Studies; Renin; Renin-Angiotensin System

Glitazones are powerful insulin sensitisers prescribed for the treatment of type 2 diabetes. Their use is, however, associated with fluid retention and an increased risk of congestive heart failure. We previously demonstrated that pioglitazone increases proximal sodium reabsorption in healthy volunteers. This study examines the effects of pioglitazone on renal sodium handling in individuals prone to insulin resistance, i.e. those with diabetes and/or hypertension.. In this double-blind randomised placebo-controlled four-way crossover study, we examined the effects of pioglitazone (45 mg daily during 6 weeks) or placebo on renal, systemic and hormonal responses to changes in sodium intake in 16 individuals, eight with type 2 diabetes and eight with hypertension.. Pioglitazone was associated with a rapid increase in body weight and an increase in diurnal proximal sodium reabsorption, without any change in renal haemodynamics or in the modulation of the renin-angiotensin aldosterone system to changes in salt intake. A compensatory increase in brain natriuretic peptide levels was observed. In spite of sodium retention, pioglitazone dissociated the blood-pressure response to salt and abolished salt sensitivity in salt-sensitive individuals.. Pioglitazone increases diurnal proximal sodium retention in diabetic and hypertensive individuals. These effects cause fluid retention and may contribute to the increased incidence of congestive heart failure with glitazones.. ClinicalTrial.gov NCT01090752. Hypertension Research Foundation Lausanne.

Topics: Analysis of Variance; Blood Pressure; Body Weight; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Humans; Hypertension; Hypoglycemic Agents; Insulin Resistance; Male; Metformin; Natriuretic Peptide, Brain; Pioglitazone; Sodium, Dietary; Thiazolidinediones

Treatment with prostaglandin inhibitors can reduce renal function and impair renal water and sodium excretion. We tested the hypotheses that a reduction in prostaglandin synthesis by ibuprofen treatment during fasting decreased renal water and sodium excretion by increased absorption of water and sodium via the aquaporin2 water channels and the epithelial sodium channels.. The effect of ibuprofen, 600 mg thrice daily, was measured during fasting in a randomized, placebo-controlled, double-blinded crossover study of 17 healthy humans. The subjects received a standardized diet on day 1, fasted at day 2, and received an IV infusion of 3% NaCl on day 3. The effect variables were urinary excretions of aquaporin2 (u-AQP2), the beta-fraction of the epithelial sodium channel (u-ENaCbeta), cyclic-AMP (u-cAMP), prostaglandin E2 (u-PGE2). Free water clearance (CH2O), fractional excretion of sodium (FENa), and plasma concentrations of vasopressin, angiotensin II, aldosterone, atrial-, and brain natriuretic peptide.. Ibuprofen decreased u-AQP2, u-PGE2, and FENa at all parts of the study. During the same time, ibuprofen significantly increased u-ENaCbeta. Ibuprofen did not change the response in p-AVP, u-c-AMP, urinary output, and free water clearance during any of these periods. Atrial-and brain natriuretic peptide were higher.. During inhibition of prostaglandin synthesis, urinary sodium excretion decreased in parallel with an increase in sodium absorption and increase in u-ENaCbeta. U-AQP2 decreased indicating that water transport via AQP2 fell. The vasopressin-c-AMP-axis did not mediate this effect, but it may be a consequence of the changes in the natriuretic peptide system and/or the angiotensin-aldosterone system. Clinical Trials Identifier: NCT00281762.

Topics: Adolescent; Adult; Aged; Albumins; Aquaporin 2; Arginine Vasopressin; Blood Pressure; Body Weight; Cross-Over Studies; Cyclic AMP; Dinoprostone; Epithelial Sodium Channels; Fasting; Female; Humans; Ibuprofen; Kidney; Male; Middle Aged; Natriuresis; Natriuretic Peptide, Brain; Prostaglandin Antagonists; Prostaglandins; Saline Solution, Hypertonic; Sodium; Young Adult

To evaluate the usefulness of monthly brain natriuretic peptide (BNP) dosage in assessing dry weight in hemodialysis patients.. Over a 2-year period, we performed in 46 hemodialysis patients monthly BNP level measurements, and adapted dry weight following the determination of variations in BNP concentrations for each month during the study period. Then we tested our approach by looking for a statistical relation between monthly alterations in BNP levels and monthly variations in the patients' weight, blood pressure, hemoglobinemia and albuminemia which are in themselves related to fluid status variations.. Monthly BNP level variations were found to be positively correlated with monthly end-dialysis weight alterations (r = +0.24, p < 0.001), with monthly systolic and diastolic blood pressure variations before dialysis (r = +0.09, p < 0.001; r = +0.24, p < 0.001), and with systolic and diastolic blood pressure changes after dialysis (r = +0.09, p = 0.001; r = +0.25, p < 0.001). Moreover, monthly BNP level variations were negatively correlated with monthly hemoglobinemia changes (r = -0.17, p = 0.004) and with monthly albuminemia alterations (r = -0.14, p = 0.001).. In a non-selected population of hemodialysis patients it was found that monthly BNP level variations were positively correlated with monthly volume status alterations as evaluated by clinical and biological criteria. BNP appears to be a useful tool for dry weight assessment despite the absence of a standardized cut-off point for BNP levels in hemodialysis patients.

Topics: Biomarkers; Blood Pressure; Blood Volume; Body Fluids; Body Weight; Female; Fluorescence Polarization Immunoassay; Follow-Up Studies; Humans; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Renal Dialysis; Retrospective Studies; Treatment Outcome

This study sought to investigate whether darbepoetin alfa, an erythropoiesis-stimulating protein (ESP), improves exercise capacity in patients with symptomatic chronic heart failure (CHF) and anemia.. Anemia is common in patients with CHF.. In a multicenter, randomized, double-blind, placebo-controlled study, CHF patients with anemia (hemoglobin > or =9.0 to < or =12.0 g/dl) received subcutaneous placebo (n = 22) or darbepoetin alfa (n = 19) at a starting dose of 0.75 microg/kg every 2 weeks for 26 weeks. The primary end point was change in exercise tolerance from baseline to week 27 as measured by peak oxygen uptake (ml/min/kg body weight). Other end points included changes in absolute peak VO2 (ml/min), exercise duration, and health-related quality of life.. Differences (95% confidence interval) in mean changes from baseline to week 27 between treatment groups were 1.5 g/dl (0.5 to 2.4) for hemoglobin concentration (p = 0.005), 0.5 ml/kg/min (-0.7 to 1.7) for peak VO2 (p = 0.40), 45 ml/min (-35 to 127) for absolute peak VO2 (p = 0.27), and 108 s (-11 to 228) for exercise duration (p = 0.075). Patients receiving darbepoetin alfa compared with placebo had an improvement in self-reported Patient's Global Assessment of Change (79% vs. 41%, p = 0.01) but no significant differences in the Kansas City Cardiomyopathy and Minnesota Living with Heart Failure Questionnaire scores. Darbepoetin alfa was well tolerated.. In patients with symptomatic CHF and anemia, darbepoetin alfa increased and maintained hemoglobin concentrations and improved health-related quality of life. A trend toward increased exercise time but not peak VO2 was observed. (Impact of Darbepoetin Alfa on Exercise Tolerance and Left Ventricular Structure in Subjects With Symptomatic Congestive Heart Failure (CHF) and Anemia; http://clinicaltrials.gov/ct/show/NCT00117234?order = 1; NCT00117234).

Topics: Activities of Daily Living; Aged; Anemia; Body Weight; Darbepoetin alfa; Double-Blind Method; Erythropoietin; Exercise Test; Exercise Tolerance; Female; Heart Failure; Hematinics; Hemoglobins; Hospitalization; Humans; Injections, Subcutaneous; Male; Natriuretic Peptide, Brain; Oxygen Consumption; Quality of Life; Treatment Outcome

Although the therapeutic strategy of serial 6-hour intravenous infusions of nesiritide for advanced chronic heart failure (HF) is currently under investigation, frequent hospital or clinic visits may present logistical challenges for many patients with HF. Therefore, a pilot study was conducted to evaluate the safety and tolerability of serial nesiritide infusions administered at home in this patient population. Twenty patients with advanced HF were enrolled into a protocol for the administration of 12 weekly intravenous infusions of nesiritide (2 microg/kg bolus, 0.01 microg/kg/min for 6 hours) at home. Blood samples and weights were obtained weekly, and clinical assessments were made at 4 and 12 weeks. During the 12-week study period, there were 3 deaths unrelated to nesiritide therapy. Six patients required >or=1 hospitalization for HF. Two of 204 infusions resulted in symptomatic hypotension, and there were no adverse renal events. Mean body weight decreased at week 4 but returned to baseline by week 12. Antibodies to nesiritide were not detected in any patient. In conclusion, serial home infusions of nesiritide in patients with advanced HF appear to be safe and well tolerated, but the efficacy of this therapeutic strategy requires definition in a larger, randomized trial.

Topics: Aged; Blood Pressure; Body Weight; Creatinine; Heart Failure; Humans; Infusions, Intravenous; Natriuretic Agents; Natriuretic Peptide, Brain; Pilot Projects; Self Administration; Treatment Outcome

Short daily hemodialysis (HD) has a protective effect against dialysis-induced hypotension (DIH). We examined whether this effect extends beyond the treatment period.. We analyzed clinical variables in 6 patients (5 with diabetes mellitus) who underwent conventional hemodialysis (CHD) for 4 h three times weekly for 12 weeks; then short daily HD for 2 h six times weekly for 12 weeks, and then 12 more weeks of CHD. All patients had been given vasopressors for severe DIH.. The severe DIH disappeared during the short daily HD. There were significant decreases in body weight (BW), cardiothoracic ratio (CTR), blood pressure (BP), normal saline solution (NSS) amount (62.8 +/- 26.4 vs. 9.8 +/- 7.4 ml/session, p < 0.05), frequency (0.60 +/- 0.26 vs. 0.10 +/- 0.07 infusions/session, p < 0.05) and postdialysis atrial natriuretic peptide (ANP) (176.8 +/- 56.4 vs. 104.8 +/- 42.3 pg/ml, p < 0.05). Weekly ultrafiltration volume (6.3 +/- 0.9 vs. 7.9 +/- 0.7 l, p < 0.05) was significantly higher during the short daily HD period than during the first CHD period. The vasopressor treatment was therefore stopped or reduced in all patients during the short daily HD period. Because DIH recurred in the second CHD period despite a significant increase in BP, the vasopressor treatment was resumed in 5 patients. BW, CTR, NSS infusion amount and frequency, or postdialysis ANP did not differ significantly between the short daily HD and second CHD periods.. The protective effect of short daily HD against DIH lasted more than 12 weeks after the treatment ended. We therefore conclude that temporary short daily HD is useful for preventing DIH.

Topics: Aged; Anemia; Antihypertensive Agents; Appointments and Schedules; Arteriovenous Shunt, Surgical; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Diabetic Nephropathies; Echocardiography; Erythropoietin; Female; Ferritins; Humans; Hypertension, Renal; Hypotension; Iron; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Quality of Life; Recombinant Proteins; Renal Dialysis; Uremia

Abnormal responses of heart rate (HR) and oxygen uptake (VO2) during exercise characterize patients after right ventricular outflow tract reconstruction (RVOTR) for congenital heart defects. However, little is known about the postexercise dynamics.. We evaluated postexercise cardiovascular dynamics in 52 patients after closure of an atrioventricular septal defect (group A), 79 patients after RVOTR (group B), and 44 control subjects. HR variability, arterial baroreflex sensitivity (BRS), plasma norepinephrine, and hemodynamics were measured. Although there was no difference between group A and control subjects, declines in HR and VO2 after light and peak exercise and in systolic blood pressure (SBP) after peak exercise were delayed in group B. Age, low-frequency component of HR variability, and plasma norepinephrine were independent determinants of early HR decline. Peak SBP and VO2 had a great impact on the corresponding recoveries. When the peak values were excluded, body weight, BRS, and right ventricular ejection fraction were independent determinants of early SBP decline. BRS and the pulmonary artery resistance were independent determinants of VO2 decline throughout recovery, and age and right systolic ventricular pressure also determined the early VO2 decline. BRS and low-frequency component of HR variability were determined independently by the number of surgical procedures.. In RVOTR patients, in addition to metabolic and autonomic maturation, surgery-related abnormal cardiac autonomic nervous activity and impaired hemodynamics have a great impact on delayed postexercise cardiovascular recovery.

Topics: Atrial Natriuretic Factor; Autonomic Nervous System; Baroreflex; Blood Pressure; Body Weight; Cardiac Surgical Procedures; Cardiovascular Physiological Phenomena; Exercise Test; Heart Defects, Congenital; Heart Rate; Heart Septal Defects; Heart Ventricles; Hemodynamics; Humans; Linear Models; Natriuretic Peptide, Brain; Norepinephrine; Oxygen Consumption; Postoperative Period; Recovery of Function; Reference Values; Respiratory Function Tests; Stroke Volume; Ventricular Outflow Obstruction

The mechanisms underlying the reduction in blood pressure that occurs with a severe energy-restricted diet were evaluated in 12 obese subjects during 8 days on a very-low-calorie diet (1.67 MJ/d) with a constant intake of 17 mmol sodium per day. The relationship between changes in blood pressure, sodium balance, plasma volume, renin-aldosterone and sympathetic nervous system activities, plasma C-terminus and N-terminus of the atrial natriuretic factor (ANF) prohormone, brain natriuretic peptide (BNP), and endothelin-1 (ET-1) concentrations was investigated. A negative sodium balance was present throughout the diet and was associated with a moderate reduction in plasma volume, a marked activation of the renin-aldosterone system, and a concomitant reduction in C- and N-terminal ANF prohormone levels. Moreover, the postural changes in N-terminal proANF and ANF secretion documented before the diet, disappeared after 8 days of dieting, in contrast to a greater postural stimulation of aldosterone and renin. A negative correlation was found between the changes of C- and N-terminal ANF prohormone levels and those of aldosterone. Urinary catecholamine excretion, BNP, and ET-1 remained unchanged. These results indicate that the decrease in blood pressure occurring during severe caloric restriction was essentially due to the reduction in the effective blood volume, as reflected by the stimulation of the renin-aldosterone system and the decrease in ANF levels. The lack of any changes in catecholamine excretion and endothelin levels suggests that peripheral vascular resistance did not change significantly in these circumstances.

Topics: Adolescent; Adult; Aldosterone; Atrial Natriuretic Factor; Blood Pressure; Blood Urea Nitrogen; Body Weight; Catecholamines; Creatinine; Data Interpretation, Statistical; Diet, Reducing; Electrolytes; Endothelin-1; Female; Food Deprivation; Heart Rate; Hormones; Humans; Hydrocortisone; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Obesity; Plasma Volume; Renin; Sodium; Starvation; Uric Acid

The objective of this investigation was to study both the pharmacokinetics and renal pharmacodynamic properties of intravenously infused urodilatin in human beings.. Twelve healthy subjects received a short-term infusion (90 minutes) of urodilatin and placebo with a graded infusion rate (from 7.5 to 15 to 30 ng.kg body weight-1.min-1) in a randomized, double-blind, crossover study design. The renal parameters were evaluated by clearance technique with the use of 51Cr-ethylenediaminetetraacetic acid, 125I-hippuran, and lithium. Urodilatin concentrations were determined by a radioimmunoassay with a urodilatin-specific antibody.. Kinetics were characterized by a high apparent volume of distribution (43.7 +/- 11.2 L), a high total body clearance (5383 +/- 581 ml/min), and a short plasma half-life (5.57 +/- 0.8 minutes). The maximal plasma urodilatin level was 177.2 +/- 25.8 pmol/L. Less than 1% of total infused urodilatin was recovered in urine. Urodilatin significantly increased glomerular filtration rate (urodilatin, 7.0%, versus placebo, -1.9%; p < 0.05), reduced effective renal plasma flow (urodilatin, -17%, versus placebo, -3%; p < 0.01), increased fractional excretion of sodium (urodilatin, 137%, versus placebo, 27%; p < 0.05), and increased urine flow rate (urodilatin, 46%, versus placebo, -15%; p < 0.01). Fractional excretion of lithium did not change. Mean blood pressure decreased and vasoactive hormone levels remained unchanged or increased.. The natriuretic and diuretic effects of urodilatin closely followed the profile of urodilatin concentration in plasma. A major part of the synthetic urodilatin was removed from circulation by a route other than filtration through the glomeruli.

Topics: Adult; Aldosterone; Angiotensin II; Arginine Vasopressin; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Cross-Over Studies; Cyclic GMP; Diuretics; Double-Blind Method; Heart Rate; Hematocrit; Humans; Infusions, Intravenous; Kidney; Lithium; Male; Metabolic Clearance Rate; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Renin; Sodium

Dry weight (DW) adjustment in children on hemodialysis (HD) can be challenging. It relies on clinical evaluation and additional supports. Our aim was to study the benefits of cardiac biomarker assessment, in addition to the more commonly used technique, bioimpedance spectroscopy (BIS), and clinical signs for DW prescription in pediatric HD patients.. Observational study including 41 children on HD in three pediatric HD centers in the Paris region. During one session, BIS was performed before the session and serum levels of BNP and NT-proBNP were analyzed before and after the session.. Median pre-dialysis level of BNP was 87 ng/L [24-192] and NT-proBNP 968 ng/L [442-4828]. Cardiac biomarker levels showed positive correlation with the BIS hydration status evaluation (p = 0.004). The most appropriate cutoff for pre-dialysis BNP to detect significant overhydration (OH) was 165 ng/L (sensitivity 0.67, specificity 0.84). Based on the BIS evaluation, only 32% of patients with high blood pressure (BP) had OH, whereas in the normal BP group, 33% had significant OH.. DW prescription for children on HD should not only rely on clinical evaluation, particularly BP, but should also include additional helpful parameters. BIS is well-validated in children, but it has limitations in non-cooperative patients, and its cost can limit its use in some settings. Cardiac biomarkers, especially BNP, were well-correlated to hydration status evaluated by BIS, and thus could add valuable information for individual patient management and DW assessment. A higher resolution version of the Graphical abstract is available as Supplementary information.

Topics: Biomarkers; Body Weight; Child; Humans; Kidney Failure, Chronic; Natriuretic Peptide, Brain; Peptide Fragments; Renal Dialysis; Water Intoxication

This study observed the effects of treadmill running on adipose tissue browning and lipolysis in rats with induced heart failure and elucidated the possible mechanism. Rats underwent abdominal aortic constriction as a model of heart failure. Cardiac function was detected by echocardiography. We detected serum levels of norepinephrine and interleukin 6, cardiac atrial natriuretic peptide and brain natriuretic peptide and marker genes of browning, white adipose tissue (WAT), and lipolysis in adipose tissue. Rats with heart failure showed typical symptoms such as increased heart weight and mRNA levels of atrial natriuretic peptide and brain natriuretic peptide and decreased left ventricular ejection fraction. Exercise partially improved left ventricular diastolic function and significantly decreased atrial natriuretic peptide expression. Rats with heart failure showed significantly reduced body weight and ratios of muscle and fat weight to body weight. Exercise significantly increased body weight and the ratio of muscle weight to body weight. Heart failure stimulated the expression of proliferator-activated receptor-gamma coactivator-1-alpha and uncoupling protein 1 in epididymal WAT, inguinal WAT, and brown adipose tissue but decreased that of adiponectin and leptin in inguinal WAT. Lipolysis, characterized by high adipose triglyceride lipase and hormone-sensitive lipase expression, was activated in all adipose tissues. Exercise reduced browning and lipolysis in adipose tissues. Rats with heart failure had abnormally high levels of serum norepinephrine and interleukin 6, which could be suppressed by exercise. Exercise may improve cardiac cachexia and inhibit the browning and lipolysis of adipose tissue by downregulating sympathetic nervous system activity and inflammation.

Topics: Adipose Tissue; Adipose Tissue, Brown; Adipose Tissue, White; Animals; Atrial Natriuretic Factor; Body Weight; Heart Failure; Interleukin-6; Lipolysis; Natriuretic Peptide, Brain; Norepinephrine; Physical Conditioning, Animal; Rats; Running; Stroke Volume; Ventricular Function, Left

Vericiguat, a novel stimulator of soluble guanylate cyclase (sGC), is indicated for the treatment of patients following a hospitalization for heart failure or need for outpatient intravenous diuretics, with symptomatic chronic heart failure and ejection fraction less than 45%. Pharmacokinetic (PK) data from the phase II trial SOCRATES-REDUCED (Soluble Guanylate Cyclase Stimulator in Heart Failure Study) and the phase III trial VICTORIA (Vericiguat Global Study in Patients With Heart Failure With Reduced Ejection Fraction) were used to characterize vericiguat PK. A total of 8,092 concentration records from 2,321 participants (362 from SOCRATES-REDUCED and 1,959 from VICTORIA) were utilized for the development of the population PK model. The final PK model was a one-compartment model with first-order absorption and linear elimination. Baseline body weight and time-varying body weight were identified as statistically significant covariates affecting apparent clearance (CL/F) and volume of distribution, respectively. Age, sex, race, bilirubin, estimated glomerular filtration rate, and albumin did not affect vericiguat PK. Baseline disease-related factors, such as left ventricular ejection fraction, New York Heart Association (NYHA) class, and N-terminal pro B-type natriuretic peptide, also did not influence vericiguat PK. Since vericiguat is a titrated drug, the impact of vericiguat PK on the titration to and maintenance of the target dose in VICTORIA was assessed. The distribution of steady-state doses in VICTORIA was similar across CL/F quartiles, suggesting that the ability to reach and maintain dosing at the target 10-mg dose was not related to vericiguat exposure.

Topics: Albumins; Bilirubin; Body Weight; Diuretics; Heart Failure; Humans; Natriuretic Peptide, Brain; Soluble Guanylyl Cyclase; Stroke Volume; Treatment Outcome; Ventricular Function, Left

Clinical studies suggest that diabetes is a risk factor in the development of pulmonary arterial hypertension. The increase in blood pressure in the pulmonary area is characterized by the increase in the afterload and hypertrophy of the right ventricle. The objective of this study was to conduct a longitudinal follow-up of the morphological and functional changes in the right ventricle in a rat model with pulmonary arterial hypertension secondary to diabetes. Male Sprague Dawley rats were randomly divided into a control group (saline solution) and a diabetic group (60 mg/kg with streptozotocin). For 12 weeks, an echocardiography for longitudinal (

Topics: Animals; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Experimental; Diastole; Echocardiography; Follow-Up Studies; Heart Failure; Heart Rate; Heart Ventricles; Hypertension, Pulmonary; Male; Natriuretic Peptide, Brain; Rats, Sprague-Dawley; Risk Factors; Streptozocin; Systole; Vascular Remodeling

Tolvaptan (TLV) carries the risk of serious side effects, and its introduction requires hospitalization. Therefore, it is important from the viewpoints of safety and medical economics to predict in advance, the patients for whom it will be effective and introduce it. The purpose of this study was to investigate the noninvasive and simple predictors for identifying TLV responders. We conducted a retrospective observational study of patients with heart failure who had TLV introduced at our hospital from January 1, 2017, to December 31, 2018. By using the body weight and BNP reduction as the effect indices, predictors of body weight and BNP reduction were extracted by logistic analysis. The sensitivity and specificity at the cutoff value obtained by ROC analysis were also examined. Among 85 subjects, urine sodium concentration >63 mEq/L [odds ratio (OR): 6.11, 95% confidence interval (CI): 1.36-27.4] was detected as a predictor of body weight reduction. The sensitivity at this cutoff value was 81%, and the specificity was 70%. Serum osmolarity>291 mOsm/L (OR: 3.76, 95% CI: 1.00-14.2), urine potassium concentration<21 mEq/L (OR: 4.45, 95% CI: 1.09-18.2), and urine sodium concentration>71 mEq/L (OR: 7.38, 95% CI: 2.05-26.6) were detected as predictors of BNP reduction. The sensitivities were 62%, 53%, and 73%, and the specificities were 58%, 68%, and 68%, respectively. Therefore, it was suggested that urine sodium concentration may be useful as a predictor of body weight and BNP decrease after TLV induction.

Topics: Aged; Aged, 80 and over; Antidiuretic Hormone Receptor Antagonists; Body Weight; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Retrospective Studies; ROC Curve; Sodium; Tolvaptan

Brain natriuretic peptide is an established, surrogate follow-up marker, strongly correlated with heart failure severity. Several other biomarkers and tests are useful for assessing the prognosis of patients with HF, such as oxidized low-density lipoprotein antibodies and C-reactive protein. Some inflammatory cells, including monocytes, lymphocytes, and neutrophils, are involved in coronary heart disease and may be useful for prognosis also. This study assessed the potential usefulness of various laboratory biomarkers in predicting long-term outcomes and hospitalization among a cohort of outpatients with chronic, advanced HF.This retrospective, 18-year follow-up study included all patients admitted to the Heart Failure Outpatient Unit in our tertiary care medical center from 2000 through 2001 due to chronic HF. Excluded were patients with malignant disease, severe stroke, active inflammatory disease, or infection. At the first visit, blood was sampled for routine analysis and biomarkers NT-proBNP, C-reactive protein, myeloperoxidase, heat shock protein, and antibodies to oxidized low density lipoprotein. left ventricular ejection fraction and New York Heart Association class class were also established. Patients were followed every 3 months. Study endpoints were mortality or first hospitalization.Among 305 study patients, HF duration ranged from 2 months to 18 years. Mean follow-up was 9.1 ± 6 years. Mean time to first hospitalization was 60 ± 58.1 months, median = 38 (range 0-179). Mortality rate was 41%. Regression analysis showed New York Heart Association class, lymphocyte count and alkaline phosphatase were independent predictors of survival, with hazard ratios of 1.0, 0.973, and 1.006, respectively (P < .05).N-terminal pro-B-type natriuretic peptide, alkaline phosphatase, and lymphocyte count are important prognostic predictors for very long-term follow-up among patients with chronic HF.

Topics: Age Factors; Aged; Aged, 80 and over; Biomarkers; Blood Pressure; Body Weight; C-Reactive Protein; Chronic Disease; Comorbidity; Female; Follow-Up Studies; Heart Failure; Heart Rate; Heat-Shock Proteins; Hematologic Tests; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Peroxidase; Retrospective Studies; Sex Factors; Ventricular Function, Left

The change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels follows a paradox imposed by strenuous endurance exercise. Previous reports showed significant body weight (BW) loss was common in ultramarathon runners. This study investigated whether the BW change and renin-angiotensin-aldosterone system activation contribute to exercise-induced NT-proBNP release.. A total of 26 participants who finished a 100 km ultramarathon in Taiwan were enrolled. For each participant, blood samples and spot urine samples were collected 1 week before the race, as well as immediately and 24 hours after the finish. BW change was recorded to monitor the hydration status.. Prolonged endurance exercise led to a substantial increase in NT-proBNP. Compared with prerace values, NT-proBNP levels significantly increased immediately after the race (24.3 ± 20.2 pg/mL to 402.9 ± 305.9 pg/mL, p < 0.05) and maintained high levels until 24 hours after the race (143.7 ± 126.1 pg/mL, p < 0.05). The fractional excretion of sodium values was below 1% in three different time points. The 100 km ultramarathon resulted in significant BW loss and elevated renin and aldosterone levels. However, only 24 hours after the race, a positive significant relationship was found between NT-proBNP and aldosterone levels (p = 0.007, r = 0.267), but a negative significant relationship between NT-proBNP and BW increased during the recovery phase (p < 0.001, r = 0.372).. The mechanism of NT-proBNP release immediately following the race was multifaceted. During the recovery phase, rehydration might lead to the decrease of NT-proBNP. Our observations with regard to aldosterone and NT-proBNP might be in response to help the body maintains hydration state.

Topics: Adult; Body Weight; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Renin-Angiotensin System; Running; Sodium

Although the evaluation of fluid status in hemodialysis (HD) patients is useful, relationship among pulmonary capillary wedge pressure (PCWP), dry body weight (DW) and natriuretic peptide has not been elucidated. In addition, there has been no objective marker for instantaneously monitoring hemodynamic improvement in response to HD. We previously reported that PCWP and time constant of left ventricular pressure decline (Tau) can be noninvasively estimated (ePCWP and eTau) by speckle tracking echocardiography (STE). The aim of this study was to elucidate the relationship among ePCWP, eTau, DW and natriuretic peptide in patients undergoing HD.. We measured ePCWP and body weight (BW) by STE in 81 patients and ANP and BNP by blood examination in 31 patients just before and after HD during sinus rhythm.. The ePCWP decreased after HD, and this was associated with reductions in ln ANP, eTau and BW (r = 0.523, 0.271 and 0.814, respectively, p < 0.05). The % change in ePCWP was not correlated with the % change in ln BNP (p = 0.47). The change in ePCWP had a stronger correlation with the % change in BW than the change in any other parameters.. The ePCWP is more sensitive to estimate the change in BW during HD than any other parameters such as ANP and BNP. These results indicated that a substantial amount of excess fluid can be assessed real-time by STE using ePCWP.

Topics: Aged; Biomarkers; Body Weight; Echocardiography, Three-Dimensional; Female; Hemodynamics; Humans; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Natriuretic Peptides; Pulmonary Wedge Pressure; Renal Dialysis

The cardiac atria secrets polypeptide hormones usually called natriuretic peptides (NPs). These substances play a relevant role in the blood pressure regulation. The objective of the study was to estimate the effects of aging on the secretory apparatus of NPs in cardiomyocytes of the right atrium. Twenty male Wistar rats were studied: 10 young animals aged 3 months old (237 ± 27 g; mean ± SD) and 10 old animals aged 20 months old (450 ± 68 g; mean ± SD). The systolic blood pressure was verified instants before the moment of the euthanasia. Electron micrographs were prepared to quantify the area and density of the NP granules and the relative volumes of the endoplasmic reticulum, Golgi complex, and mitochondria. In addition, the number of pores per 10 μm of karyotheca was another variable evaluated. The significance of the results between the two groups evaluated was analyzed by the Student's t test (p < 0.05). The cardiomyocytes obtained from animals of the old group showed decreased in sectional area and density of secretory granules of NP and lower relative volume of endoplasmic reticulum, Golgi complex, and mitochondria compared with the young rats. Moreover, the quantitative density of nuclear pores was significantly lower compared with the youngers. CONCLUSION: Aging causes hypotrophy of the cardiomyocytes of right atrium, similar to what occurs in ventricular cardiomyocytes.

Topics: Aging; Animals; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Heart Atria; Heart Ventricles; Male; Myocytes, Cardiac; Natriuretic Peptide, Brain; Rats; Rats, Wistar

Cardiac hypertrophy is a risk factor which can intrigue heart failure. In the present study, we explored whether AdipoRon attenuates isoprenaline (ISO) or l-thyroxine-induced cardiac hypertrophy in Sprague-Dawley (SD) rats and whether the anti-hypertrophy effect is mediated by AMPK-related pathway. Here, cardiac hypertrophy was induced by injection of l-thyroxine or ISO in SD rats. In the treatment group, AdipoRon was co-administered. We examined the effects of AdipoRon on cardiac hypertrophy and hypertrophy signaling pathway. The weight of SD rats was recorded every day. Rats were killed for collection of blood and heart under anesthesia. The left heart weight and heart weight were weighed. Paraffin-embedded heart tissue regions (4 μm) were stained with hematoxylin and eosin or Masson to detect left heart hypertrophy and myocardial fibrosis. The serum BNP levels were determined by using an enzyme-linked immunosorbent assay. The mRNA levels of ANP, BNP, PGC-1α, and ERRα were evaluated by real-time PCR analysis. The protein expression levels of PGC-1α, ERRα, and pAMPK/AMPK were determined by western blot analysis. The results showed that AdipoRon significantly reversed heart weight (HW)/body weight (BW) ratio, left ventricular (LV)/BW ratio, serum BNP level and the mRNA level of ANP and BNP induced by ISO or l-thyroxine. ISO or l-thyroxine reduced both the mRNA level and protein level of ERRα and PGC-1α, and also reduced the protein level of pAMPK/AMPK. However, AdipoRon reversed ISO or l-thyroxine-induced changes of pAMPK/AMPK, ERRα, and PGC-1α. Our data indicated that the effects of AdipoRon are mediated partly by activating AMPK-related pathway, and AdipoRon plays a potential role in the prevention of cardiac hypertrophy.

Topics: AMP-Activated Protein Kinases; Animals; Atrial Natriuretic Factor; Body Weight; Cardiomegaly; Gene Expression; Isoproterenol; Male; Natriuretic Peptide, Brain; Organ Size; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Piperidines; Rats, Sprague-Dawley; Signal Transduction; Thyroxine

Prognostication of patients discharged after acute heart failure (AHF) hospitalization remains challenging. Body weight (BW) reduction is often used as a surrogate marker of decongestion despite the paucity of evidence. We thought to test the hypothesis that B-type natriuretic peptide (BNP) reduction during hospitalization has independent prognostic value in AHF.. We studied the prognostic predictability of percentage BNP reduction achieved during hospitalization in patients from the REALITY-AHF study. Percentage BNP reduction was defined as (BNP on admission - BNP at discharge) / BNP on admission × 100. The primary endpoint was 1-year all-cause death. In 1028 patients (age, 77 ± 13 years; 57% male; left ventricular ejection fraction, 47 ± 16%) with AHF, median BNP level at admission was 747 ng/L (interquartile range, 439-1367 ng/L) and median percentage BNP reduction was 62.5% (interquartile range, 36.5-78.5%). The smallest percentage BNP reduction quartile had more than 2-fold higher risk of all-cause death than the greatest quartile (23.0% vs 9.7%, P< .001). After adjusting for covariates including BNP at discharge, the percentage BNP reduction was significantly associated with all-cause death (hazard ratio 0.96, 95% confidence interval 0.93-0.99, P= .032), whereas percentage BW reduction was not. Percentage BNP reduction was more predictive in patients with heart failure with reduced ejection fraction than in those with preserved ejection fraction.. The prognostic value of percentage BNP reduction during hospitalization was superior to that of percentage BW reduction and was independent of other risk markers, including BNP at discharge.

Topics: Acute Disease; Aged; Biomarkers; Body Weight; Female; Heart Failure; Hospitalization; Humans; Japan; Male; Mortality; Natriuretic Peptide, Brain; Patient Discharge; Predictive Value of Tests; Prognosis; Registries; Risk Assessment; Stroke Volume

Diabetes mellitus (DM) has been demonstrated to have a strong association with heart failure. Conventional echocardiographic analysis cannot sensitively monitor cardiac dysfunction in type I diabetic Akita hearts, but the phenotype of heart failure is observed in molecular levels during the early stages.. Male Akita (Ins2WT/C96Y) mice were monitored with echocardiographic imaging at various ages, and then with conventional echocardiographic analysis and speckle-tracking based strain analyses.. With speckle-tracking based strain analyses, diabetic Akita mice showed changes in average global radial strain at the age of 12 weeks, as well as decreased longitudinal strain. These changes occurred in the early stage and remained throughout the progression of diabetic cardiomyopathy in Akita mice. Speckle-tracking showed that the detailed and precise changes of cardiac deformation in the progression of diabetic cardiomyopathy in the genetic type I diabetic Akita mice were uncoupled.. We monitored early-stage changes in the heart of diabetic Akita mice. We utilize this technique to elucidate the underlying mechanism for heart failure in Akita genetic type I diabetic mice. It will further advance the assessment of cardiac abnormalities, as well as the discovery of new drug treatments using Akita genetic type I diabetic mice.

Topics: Animals; Atrial Natriuretic Factor; Blood Glucose; Body Weight; Diabetes Mellitus, Type 1; Diabetic Cardiomyopathies; Disease Models, Animal; Echocardiography; Female; Heart; Heart Rate; Heart Ventricles; Male; Mice; Mice, Inbred C57BL; Myocardium; Natriuretic Peptide, Brain; Severity of Illness Index; Ventricular Dysfunction, Left

Natriuretic peptide type B (BNP) is a marker of myocardium injury. This peptide has been associated with metabolic risk markers, although controversy exists in this regard. The aim of the present study was to determine the correlation of plasma BNP levels with metabolic risk parameters.. A retrospective, observational study that included 152 patients, who were classified according to their clinical diagnosis as patients with metabolic syndrome. Plasma BNP levels and clinical metabolic parameters were assessed by using Spearmańs rank correlation coefficient.. A significant inverse association with weight (r=-.408; p<.0001) and BMI (r=-.443; p<.001) was obtained. While a positive significant association with systolic pressure (r=.324; p<.001) was observed. A significant decrease was found in BNP levels and components of metabolic syndrome. (p<.05).. Based on the results from this study, we can conclude that BNP determination could be an adequate metabolic marker.

Topics: Biomarkers; Blood Pressure; Body Weight; Cross-Sectional Studies; Female; Humans; Male; Metabolic Syndrome; Middle Aged; Natriuretic Peptide, Brain; Retrospective Studies; Statistics, Nonparametric

Cholecystokinin (CCK) is expressed in cardiomyocytes and may also play an important role in cardiovascular regulation. Clinical studies have shown that plasma CCK levels are an independent marker of cardiovascular mortality in cardiac disease. However, whether the development of postinfarction heart failure is associated with changes in CCK expression is unknown.. To investigate CCK expression patterns and the association between CCK expression and heart functional parameters, we randomized male Sprague-Dawley rats into myocardial infarction (MI) or sham operation (SO) groups. CCK expression levels were assessed by western blotting, immunohistochemistry, real-time polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay (ELISA) at different time points (2, 4 or 6 weeks) after surgery. Brain natriuretic peptide (BNP) concentrations were determined using Western blotting and ELISA, myocardial morphology was assessed by microscopy.. Plasma CCK and BNP levels were significantly increased in all the MI groups compared with the corresponding SO groups. However, the degree to which myocardial CCK mRNA and protein expression levels were increased the MI groups compared with the SO groups was greater in the 4- and 6-week groups than in the 2-week group. Furthermore, plasma CCK levels were positively correlated with BNP concentrations and left ventricular end-systolic diameter (LVDs) and significantly negatively correlated with the ejection fraction (EF) and shortening fraction (SF) in model animals.. Heart failure progression after infarction is associated with upregulated CCK levels; thus, CCK may be useful as a novel marker of heart failure.

Topics: Animals; Biomarkers; Body Weight; Cholecystokinin; Disease Models, Animal; Echocardiography; Enzyme-Linked Immunosorbent Assay; Fibrosis; Heart; Heart Failure; Immunohistochemistry; Male; Myocardial Infarction; Myocardium; Natriuretic Peptide, Brain; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction

BACKGROUND Heart failure in women increases around the time of menopause when high-fat diets may result in obesity. The heart produces brain natriuretic peptide (BNP), also known as B-type natriuretic peptide. This aims of this study were to assess cardiac hypertrophy and BNP levels in ovariectomized rats fed a high-fat diet. MATERIAL AND METHODS Forty-eight female Wistar rats were divided into four groups: sham-operated rats fed a control diet (SC) (n=12); ovariectomized rats fed a control diet (OC) (n=12); sham-operated rats fed a high-fat diet (SF) (n=12); and ovariectomized rats fed a high-fat diet (OF) (n=12). Body weight and blood pressure were measured weekly for 24 weeks. Rats were then euthanized, and plasma samples and heart tissue were studied for gene expression, hydroxyproline levels, and histological examination. RESULTS A high-fat diet and ovariectomy (group OF) increased the weight body and the systolic blood pressure after three months and five months, respectively. Cardiomyocyte hypertrophy was associated with increased expression of ventricular BNP, decreased natriuretic peptide receptor (NPR)-A and increased levels of hydroxyproline and transforming growth factor (TGF)-β. The plasma levels of BNP and estradiol were inversely correlated; expression of estrogen receptor (ER)β and ERα were reduced. CONCLUSIONS The findings of this study showed that, in the ovariectomized rats fed a high-fat diet, the BNP-NPR-A receptor complex was involved in cardiac remodeling. BNP may be a marker of cardiac hypertrophy in this animal model.

Topics: Animals; Blood Pressure; Body Weight; Cardiomegaly; Diet, High-Fat; Disease Models, Animal; Estradiol; Female; Gene Expression; Heart Ventricles; Myocytes, Cardiac; Natriuretic Peptide, Brain; Obesity; Ovariectomy; Rats; Rats, Wistar; Receptors, Atrial Natriuretic Factor

The normal range of plasma brain natriuretic peptide (BNP) in pregnant women is still unclear. Moreover, pregnant women experience dynamic body weight changes and suffer from anemia, but effects on maternal BNP have not been investigated. This study aimed to reveal the normal plasma BNP range and examine the effects of physiological changes on BNP among pregnant women.. Plasma BNP, hemoglobin, plasma creatinine and BMI were measured in 58 non-pregnant control women and in 773 normal pregnant women at late pregnancy, early postpartum and 1-month postpartum. Mean plasma BNP (in pg/mL) was 11.8 (95% confidence interval: 0-27.5) in non-pregnant women, 17.9 (0-44.7, p<0.001) at late pregnancy, 42.5 (0-112.6, p<0.001) early postpartum and 16.1 (0-43.9, p=0.001) 1-month postpartum. Multiple regression analysis revealed that pre-delivery BNP levels were negatively correlated with BMI (p<0.001) and hemoglobin (p=0.002) and positively correlated with creatinine (p<0.001). Post-delivery BNP was positively associated with body weight change during pregnancy (p=0.001) and post-delivery creatinine (p=0.010) but negatively associated with body weight loss at delivery (p<0.001) and post-delivery hemoglobin (p=0.004).. Even normal pregnancy affects plasma BNP, particularly in the early postpartum period, indicative of cardiac stress. Plasma BNP levels are affected by BMI, body weight changes, creatinine and hemoglobin levels; therefore, these factors should be considered when analysing cardiac function and the physiological implications of BNP levels in pregnant women.

Topics: Adult; Body Weight; Cohort Studies; Creatinine; Female; Hemoglobins; Humans; Natriuretic Peptide, Brain; Postpartum Period; Pregnancy; Reference Values

Fetal undernutrition is a risk factor for heart disease in both genders, despite the protection of women against hypertension development. Using a rat model of maternal undernutrition (MUN) we aimed to assess possible sex differences in the development of cardiac alterations and the implication of hypertension and cardiac oxidative stress.. Male and female offspring from rats fed ad libitum (control) or with 50% of the normal daily intake during the second half of gestation (MUN) were used. Heart weight/body weight ratio (HW/BW), hemodynamic parameters (anaesthetized rats) and plasma brain natriuretic peptide (BNP, ELISA) were assessed in 21-day, 6-month and 22-month old rats. Plasma testosterone (ELISA) and cardiac protein expression of enzymes related to reactive oxygen species synthesis (p22phox, xanthine-oxidase) and degradation (catalase, Cu/Zn-SOD, Mn-SOD, Ec-SOD) were evaluated in 21-day and 6-month old rats (Western Blot). Heart structure and function was studied at the age of 22 months (echocardiography).. At the age of 21 days MUN males exhibited significantly larger HW/BW and cardiac p22phox expression while females had reduced p22phox expression, compared to their respective sex-matched controls. At the age of 6-months, MUN males showed significantly larger blood pressure and cardiac xanthine-oxidase expression; MUN females were normotensive and had a lower cardiac expression of antioxidant enzymes, compared to their respective sex-matched controls. At the age of 22 months, both MUN males and females showed larger HW/BW and left ventricular mass and lower ejection fraction compared to sex-matched controls; only MUN males exhibited hypertension and a larger plasma BNP compared to aged male controls.. 1) During perinatal life females exposed to fetal undernutrition are protected from cardiac alterations, but in ageing they exhibit ventricular hypertrophy and functional loss, like MUN males; 2) cardiac oxidative stress might be implicated in the observed heart alterations in both sexes and 3) the severity of cardiac damage might be greater in males due to hypertension.

Topics: Animals; Body Weight; Female; Fetal Nutrition Disorders; Hemodynamics; Hormones; Hypertension; Male; Mothers; Myocardium; Natriuretic Peptide, Brain; Organ Size; Oxidative Stress; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Risk Factors; Sex Characteristics; Time Factors

Diabetic cardiomyopathy (DCM) is one of the most common causes of mortality. Its pathophysiology is not fully understood and involve number of factors including, cardiovascular and metabolic disorders. The present study was designed to study the pathogenesis of DCM and to explore the effects of levosimendan along with either ramipril or insulin in the long term management of DCM.. Streptozotocin (STZ) was used to develop DCM in Wistar rats at the dose of 25mg/kg body weight for three consecutive days. Rats were randomly divided into 9 groups and treatments were started after 2weeks of STZ administration.. Persistent hyperglycemia was observed in STZ treated rats, leading to significant contractile dysfunction as evidenced by decreased left ventricular pressure (LVP), +LV (dp/dt), -LV (dp/dt) as well as elevated Tau and LVEDP. Marked myocardial damage such as fibrosis, increased wall tension, depletion of contractile proteins were observed as evidenced by increased levels of TGF-β, BNP, cTroponin-I, as well as decreased expression of SERCA2a and NCX1 proteins in diabetic rats. The levosimendan alone and also in combination with either ramipril or insulin significantly normalized the myocardial dysfunctions developed during the course of persistent hyperglycemia.. The study suggests that levosimendan treatment improves cardiac dysfunction significantly. Its combined use with ramipril proves better than with insulin in correcting myocardial performance as well as reduction in myocardial damage.

Topics: Animals; Body Weight; Cardiomyopathies; Cardiotonic Agents; Diabetes Mellitus, Experimental; Heart; Hemodynamics; Hydrazones; Male; Natriuretic Peptide, Brain; Nitric Oxide; Pyridazines; Rats; Rats, Wistar; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Simendan; Sodium-Calcium Exchanger; Streptozocin; Transforming Growth Factor beta; Troponin I

Adaptive servo-ventilation (ASV) therapy using an innovative ventilator-originally developed to treat sleep-disordered breathing (SDB)-is a novel modality of noninvasive positive pressure ventilation and is gaining acceptance among Japanese cardiologists in expectation of its applicability to treat patients with chronic heart failure (CHF) based on its acute beneficial hemodynamic effects. We conducted a multicenter, retrospective, real-world observational study in 115 Japanese patients with CHF, who had undergone home ASV therapy for the first time from January through December 2009, to examine their profile and the effects on their symptoms and hemodynamics. Medical records were used to investigate New York Heart Association (NYHA) class, echocardiographic parameters including left ventricular ejection fraction (LVEF), cardiothoracic ratio (CTR), brain natriuretic peptide (BNP), and other variables. Most of the patients were categorized to NYHA classes II (44.4 %) and III (40.7 %). SDB severity was not determined in 44 patients, and SDB was not detected or was mild in 27 patients. In at least 71 patients (61.7 %), therefore, ASV therapy was not applied for the treatment of SDB. CHF was more severe, i.e., greater NYHA class, lower LVEF, and higher CTR, in 87 ASV-continued patients (75.7 %) than in 28 ASV-discontinued patients (24.3 %). However, SDB severity was not related to continuity of ASV. The combined proportion of NYHA classes III and IV (P = 0.012) and LVEF (P = 0.009) improved significantly after ASV therapy. CTR and BNP did not improve significantly after ASV therapy but showed significant beneficial changes in their time-course analysis (P < 0.05, respectively). Improvements in LVEF and NYHA class after ASV therapy were not influenced by SDB severity at onset. The present study suggests that ASV therapy would improve the symptoms and hemodynamics of CHF patients, regardless of SDB severity. A randomized clinical study to verify these effects is warranted.

Topics: Aged; Body Weight; Chronic Disease; Echocardiography; Female; Heart Failure; Hemodynamics; Humans; Japan; Logistic Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Positive-Pressure Respiration; Retrospective Studies; Severity of Illness Index; Sleep Apnea Syndromes; Treatment Outcome; Ventilators, Mechanical; Ventricular Function, Left

This study examined the sex differences for physical, morphological, histological, mRNA, and protein expression levels changes for interleukins and natriuretic peptides in left ventricle (LV) of two groups of adult FVB/N mice; males (WM) and females (WF). LV morphological, histological, reverse transcription and quantitative real-time PCR (RT-PCR), and immunohistochemical (IHC) alterations were determined in FVB/N mice at 34-35 weeks on gender basis. Confirming the gender dimorphism, FVB/N males (WM) illustrated a significant reduction in ANP and IL1-A levels as well as significantly increased body weight (BW (gm)), tibia length (TL (mm)), heart weight (HW (mg)), heart weight-to-body weight (HW/BW (mg/gm)) ratio, heart weight-to-tibia length (HW/TL (mg/mm)) ratio, left ventricle weight (LV (mg)), left ventricle-to-body weight (LV/BW (mg/gm)) ratio, and left ventricle-to-tibia length (LV/TL (mg/mm)) ratio, left ventricular (LV) cardiomyocyte diameter, high BNP, NPRA, IL-1B, and IL1R1 expression in comparison with FVB/N females (WF). Gender differences in relation to left ventricle (LV) may be due to differences in the interleukins and natriuretic peptides levels as an outcome of sex related hormones.

Topics: Animals; Atrial Natriuretic Factor; Body Weight; Female; Heart Ventricles; Interleukins; Male; Mice; Myocardium; Myocytes, Cardiac; Natriuretic Peptide, Brain; Organ Size; Real-Time Polymerase Chain Reaction; Receptors, Atrial Natriuretic Factor; Receptors, Interleukin-1 Type I; Sex Characteristics; Tibia

To evaluate whether changes in hydration status (reflecting fluid retention) would be detected by bioelectrical impedance vector analysis (BIVA) and phase angle during hospitalization for acute decompensated heart failure (ADHF) and after clinical stabilization.. Patients admitted to ADHF were evaluated at admission, discharge and after clinical stabilization (3 mo after discharge) for dyspnea, weight, brain natriuretic peptide, bioelectrical impedance resistance, reactance, and phase angle. Generalized estimating equations and chi-square detected variations among the three time points of evaluation.. Were included 57 patients: Mean age was 61 ± 13 y, 65% were male, LVEF was 25 ± 8%. During hospitalization there were improvements in clinical parameters and increase in resistance/height (from 250 ± 72 to 302 ± 59 Ohms/m, P < 0.001), reactance/height (from 24 ± 10 to 31 ± 9 Ohms/m, P < 0.001), and phase angle (from 5.3 ± 1.6 to 6 ± 1.6°, P = 0.007). From discharge to chronic stability, both clinical and BIVA parameters remained stable. At admission, 61% of patients had significant congestion by BIVA, and they lost more weight and had higher improvement in dyspnea during hospitalization (P < 0.05). At discharge, more patients were in the upper half of the graph (characterizing some degree of dehydration) while at chronic stability normal hydration status was more prevalent (P < 0.001).. BIVA and phase angle were able to detect significant changes in hydration status during ADHF, which paralleled the clinical course of recompensation, both acutely and chronically. The classification of congestion by BIVA at admission identified patients with more pronounced changes in weight and dyspnea during compensation.

Topics: Acute Disease; Aged; Body Composition; Body Weight; Cohort Studies; Dyspnea; Electric Impedance; Female; Follow-Up Studies; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Water-Electrolyte Imbalance

Growth hormone and its mediator, insulinlike growth factor 1 (IGF-1), are key determinants of growth in children and young adults. As patients with Fontan physiology often experience diminished longitudinal growth, we sought to describe IGF-1 levels in this population and to identify factors associated with IGF-1 deficiency. Forty-one Fontan subjects ≥5 years were evaluated in this cross-sectional study. Age- and gender-specific height Z scores were generated using national data. Laboratory testing included IGF-1 and brain natriuretic peptide (BNP) levels. IGF-1 levels were converted to age-, gender-, and Tanner stage-specific Z scores. BNP levels were log transformed to achieve a normal distribution (log-BNP). Medical records were reviewed for pertinent clinical variables. Predictors of IGF-1 Z score were assessed through the Student t test and Pearson's correlation. Median age was 11.1 years (range 5.1 to 33.5 years), and time from Fontan was 8.2 years (1.1 to 26.7). Mean height Z score was -0.2 ± 0.9 with a mean IGF-1 Z score of -0.1 ± 1.3. There was no association between IGF-1 Z score and height Z score. Longer interval since Fontan (R = -0.32, p = 0.04), higher log-BNP (R = -0.40; p = 0.01), and lower indexed systemic flow on cardiac magnetic resonance (R = 0.55, p = 0.02) were associated with lower IGF-1 Z scores. In conclusion, in this cohort with Fontan physiology, higher BNP and lower systemic flow were associated with lower IGF-1 Z score. Longitudinal studies are needed to determine if these relations represent a mechanistic explanation for diminished growth in children with this physiology and with other forms of congenital heart disease.

Topics: Adolescent; Adult; Biomarkers; Body Height; Body Weight; Child; Child, Preschool; Cross-Sectional Studies; Female; Fontan Procedure; Heart Defects, Congenital; Heart Failure; Humans; Insulin-Like Growth Factor I; Male; Natriuretic Agents; Natriuretic Peptide, Brain; Palliative Care; Predictive Value of Tests; Prognosis; Reproducibility of Results; Risk Factors; Sensitivity and Specificity; Severity of Illness Index; Time Factors; Young Adult

This study aimed to evaluate cardiorespiratory and hemodynamic responses during 24 h of continuous cycle ergometry in ultraendurance athletes.. Eight males (mean ± SD; age = 39 ± 8 yr, height = 179 ± 7 cm, body weight [Wt] = 77.1 ± 6.0 kg) were monitored during 24 h at a constant workload,∼25% below the first lactate turn point at 162 ± 23 W. Measurements included Wt, HR, oxygen consumption (V˙O2), cardiac output (Q), and stroke volume (SV) determined by a noninvasive rebreathing technique (Innocor; Innovision, Odense, Denmark). Myocardial dimensions were evaluated using a two-dimensional echocardiogram. [M-mode measurement]-left atrial (LAD), ventricular end-diastolic (LVEDD), and end-systolic diameters (LVESD) were obtained over the left parasternal area. Venous blood samples were analyzed for hematocrit (Hct%), albumin (g·L(-1)), aldosterone (pg·mL(-1)), CK, CK-MB (U·L(-1)), and N-terminal pro-brain natriuretic peptide (NT-proBNP) (pg·mL(-1)).. HR (bpm) significantly increased (P < 0.01) from 1 h (132 ± 11) to 6 h (143 ± 10) and significantly decreased (P < 0.001) from 6 to 24 h (116 ± 10). V˙O2 and (Q were unchanged during the 24 h. Wt (76.6 ± 5.6 vs 78.7 ± 5.4), SV (117 ± 13 vs 148 ± 19), LVEDD (4.9 ± 0.3 vs 5.6 ± 0.2), and LAD (3.6 ± 0.5 vs 4.3 ± 0.7) significantly increased between 6 and 24 h (P < 0.001). No significant changes were observed for LVESD. Hct (45.1 ± 1.3 vs 41.3 ± 1.2) significantly decreased (P < 0.05) and CK (181 ± 60/877 ± 515), aldosterone (48 ± 17 vs 661 ± 172), and NT-proBNP (23 ± 13 vs 583 ± 449) significantly increased (P < 0.05). The increase in SV (ΔSV) was significantly related to changes in Wt (ΔWt), and HR (ΔHR) and ΔWt were significantly related to ΔLAD and ΔLVEDD.. Our findings suggest that the decrease in HR during 24 h of ultraendurance exercise was due to hypervolemia and the associated ventricular loading, increasing left ventricular diastolic dimensions because of increased SV and LVEDD, resulting in an increase in NT-proBNP.

Topics: Adult; Aldosterone; Body Weight; Echocardiography; Exercise Test; Heart; Heart Rate; Hematocrit; Hemodynamics; Humans; Male; Middle Aged; Monitoring, Physiologic; Natriuretic Peptide, Brain; Organ Size; Oxygen Consumption; Peptide Fragments; Physical Endurance; Serum Albumin; Stroke Volume; Time Factors

Acromegaly is associated with an increased incidence of cardiovascular disease. Transgenic mice expressing bovine GH (bGH) gene have previously been used to examine the effects of chronic GH stimulation on cardiovascular function. Results concerning systolic blood pressure (SBP) in bGH mice are conflicting. We hypothesized that these discrepancies may be the result of the various ages of the mice used in previous studies. In the current study, SBP was assessed monthly in male bGH mice from 3-12 months of age. Factors known to alter blood pressure were assessed during this time and included: levels of brain natriuretic peptide (BNP) and glucose homeostasis markers, and renal levels of angiotensin-converting enzyme 2 and endothelial nitric oxide synthase. Beginning at 6 months of age bGH had increased SBP compared with wild-type controls, which remained elevated through 12 months of age. Despite having increased blood pressure and cardiac BNP mRNA, bGH mice had decreased circulating levels of BNP. Additionally, bGH mice had an age-dependent decline in insulin levels. For example, they were hyperinsulinemic at 3 months, but by 11 months of age were hypoinsulinemic relative to wild-type controls. This decrease in insulin was accompanied by improved glucose tolerance at 11 months. Finally, both angiotensin-converting enzyme 2 and endothelial nitric oxide synthase expression were severely depressed in kidneys of 11-month-old bGH mice. These results indicate that elevated SBP in bGH mice is dependent on age, independent of insulin resistance, and related to alterations in both the natriuretic peptide and renin-angiotensin systems.

Topics: Acromegaly; Angiotensin-Converting Enzyme 2; Animals; Blood Pressure; Body Composition; Body Weight; Cattle; Disease Models, Animal; Fibrosis; Gene Expression Regulation; Glucose; Glucose Tolerance Test; Growth Hormone; Homeostasis; Hypertension; Insulin; Kidney Glomerulus; Male; Mice; Mice, Transgenic; Natriuretic Peptide, Brain; Nitric Oxide Synthase Type III; Peptidyl-Dipeptidase A; Renin-Angiotensin System; Systole; Time Factors

Myocarditis and dilated cardiomyopathy (DCM) are inflammatory diseases of the myocardium, for which appropriate treatment remains a major clinical challenge. Oleanolic acid (OA), a natural triterpene widely distributed in food and medicinal plants, possesses a large range of biological effects with beneficial properties for health and disease prevention. Several experimental approaches have shown its cardioprotective actions, and OA has recently been proven effective for treating Th1 cell-mediated inflammatory diseases; however, its effect on inflammatory heart disorders, including myocarditis, has not yet been addressed. Therefore, the present study was undertaken to determine the effectiveness of OA in prevention and treatment of experimental autoimmune myocarditis (EAM). The utility of OA was evaluated in vivo through their administration to cardiac α-myosin (MyHc-α614-629)-immunized BALB/c mice from day 0 or day 21 post-immunization to the end of the experiment, and in vitro through their addition to stimulated-cardiac cells. Prophylactic and therapeutic administration of OA dramatically decreased disease severity: the heart weight/body weight ratio as well as plasma levels of brain natriuretic peptide and myosin-specific autoantibodies production were significantly reduced in OA-treated EAM animals, compared with untreated ones. Histological heart analysis showed that OA-treatment diminished cell infiltration, fibrosis and dystrophic calcifications. OA also decreased proliferation of cardiac fibroblast in vitro and attenuated calcium and collagen deposition induced by relevant cytokines of active myocarditis. Furthermore, in OA-treated EAM mice the number of Treg cells and the production of IL-10 and IL-35 were markedly increased, while proinflammatory and profibrotic cytokines were significantly reduced. We demonstrate that OA ameliorates both developing and established EAM by promoting an antiinflammatory cytokine profile and by interfering with the generation of cardiac-specific autoantibodies, as well as through direct protective effects on cardiac cells. Therefore, we envision this natural product as novel helpful tool for intervention in inflammatory cardiomyopathies including myocarditis.

Topics: Animals; Autoantibodies; Autoimmune Diseases; Body Weight; Calcium; Cardiomyopathy, Dilated; Cardiotonic Agents; Cell Proliferation; Female; Fibroblasts; Humans; Immunomodulation; Interleukin-10; Interleukins; Male; Mice; Mice, Inbred BALB C; Myocarditis; Myocardium; Myosin Heavy Chains; Natriuretic Peptide, Brain; Oleanolic Acid; Organ Size; Peptides; T-Lymphocytes, Regulatory

Episodes of hospitalization for heart failure patients are frequent and are often accompanied by fluid accumulations. The change of the body impedance, measured by bioimpendace spectroscopy, is an indicator of the water content. The hypothesis was that it is possible to detect edema from the impedance data. First, a finite integration technique was applied to test the feasibility and allowed a theoretical analysis of current flows through the body. Based on the results of the simulations, a clinical study was designed and conducted. The segmental impedances of 25 patients suffering from heart failure were monitored over their recompensation process. The mean age of the patients was 73.8 and their mean body mass index was 28.6. From these raw data the model parameters from the Cole model were deduced by an automatic fitting algorithm. These model data were used to classify the edema status of the patient. The baseline values of the regression lines of the extra- and intracellular resistance from the transthoracic measurement and the baseline value of the regression line of the extracellular resistance from the foot-to-foot measurement were identified as important parameters for the detection of peripheral edema. The rate of change of the imaginary impedance at the characteristic frequency and the mean intracellular resistance from the foot-to-foot measurement were identified as important parameters for the detection of pulmonary edema. To classify the data, two decision trees were considered: One should detect pulmonary edema (n(pulmonary) = 13, n(none) = 12) and the other peripheral edema (n(peripheral) = 12, n(none) = 13). Peripheral edema could be detected with a sensitivity of 100% and a specificity of 90%. The detection of pulmonary edema showed a sensitivity of 92.31% and a specificity of 100%. The leave-one-out cross-validation-error for the peripheral edema detection was 12% and 8% for the detection of pulmonary edema. This enables the application of BIS as an early warning system for cardiac decompensation with the potential to optimize patient care.

Topics: Aged; Body Fluids; Body Weight; Computer Simulation; Decision Trees; Dielectric Spectroscopy; Electric Impedance; Electrodes; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Edema

Arterial stiffness is an established cardiovascular risk marker and an independent predictor of cardiovascular events and mortality in various groups of patients, including renal transplant recipients. Recent studies have noted that B-type natriuretic peptide (BNP) acts as a local paracrine molecule that modulates endothelial permeability and regeneration. The aim of this study was to evaluate the relationship between the serum N-terminal pro-BNP (NT-pro-BNP) level and arterial stiffness in renal transplant recipients.. Fasting blood samples were obtained from 66 renal transplant recipients. The cardio-ankle vascular index was calculated using the waveform device (CAVI-VaSera VS-1000). The serum NTpro-BNP levels were measured using an electrochemiluminescence immunoassay. A CAVI value of ≥9 was used to define a high level of arterial stiffness.. Thirty-two patients (48.5%) were classified into the high arterial stiffness group. Diabetes (p=0.030), smoking (p<0.001), duration of kidney transplantation (p=0.001), body weight (p=0.014), waist circumference (p=0.022), body mass index (p=0.001) and the fasting glucose (p=0.021) and serum NT-pro-BNP (p<0.001) levels were higher in the high arterial stiffness group than in the low arterial stiffness group. A multivariate forward stepwise linear regression analysis showed that the log-NT-pro-BNP level (β: 0.459, p<0.001) remained an independent predictor of the CAVI value in the renal transplant recipients.. The serum fasting NT-pro-BNP level is associated with arterial stiffness in renal transplant recipients.

Topics: Adult; Aged; Ankle Joint; Body Mass Index; Body Weight; Electrochemistry; Female; Humans; Immunoassay; Kidney Transplantation; Luminescence; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Renal Insufficiency; Risk Factors; Smoking; Vascular Stiffness

Ultrafiltration (UF) is a widely used technology for inpatient management of acute decompensated heart failure in patients with volume overload. However, the safety and efficacy of UF in patients with heart failure and preserved left ventricular ejection fraction (heart failure with preserved ejection fraction [HFPEF]) need further clarification. We hypothesized that UF could be used in this population with outcomes similar to acute decompensated heart failure patients with low left ventricular ejection fraction (HFLEF).. Prospective evaluation was performed on 2 patient cohorts admitted to a single institution for acute decompensated heart failure and treated with UF: HFLEF (left ventricular ejection fraction ≤ 40%; n=87) and HFPEF (left ventricular ejection fraction >40%; n=97). Selected demographic and clinical data were compared, including clinical and serological information, as well as in-hospital and 90-day postdischarge mortality. HFPEF patients were more likely to be women, have higher blood pressures, and less likely to have ischemic heart disease. There were no significant differences in total weight loss (7.7% in HFLEF and 7.0% in HFPEF), electrolyte and renal disturbances, or in-hospital mortality (3.4% in HFLEF and 3.3% in HFPEF) between the 2 groups. Mortality at 90 days tended to be greater in HFLEF (24.1%) than in HFPEF (15.5%).. Therapeutic responses in patients with HFPEF meeting current indication for UF are similar to those with HFLEF. Larger studies are warranted to better characterize acute heart failure management with UF in this population.

Topics: Aged; Body Weight; Diuretics; Female; Furosemide; Heart Failure; Humans; Length of Stay; Male; Middle Aged; Natriuretic Peptide, Brain; Proportional Hazards Models; Prospective Studies; Stroke Volume; Systole; Ultrafiltration; Ventricular Function, Left

This study aimed to investigate the effects of rosuvastatin on TGF-beta1 expression, cardiac fibrosis, ventricular remodeling and cardiac function in diabetic cardiomyopathy rats. Twenty-seven diabetic rats induced by streptozotocin intraperitoneal injection were randomly divided into three groups, viz. diabetic, rosuvastatin low-dose (Ros-L) and high dose group (Ros-H). Intervention group were given rosuvastatin 2 mg/kg/d and 5 mg/kg/d orally, respectively. After 10 weeks, the levels of glycosylated hemoglobin (HbA1c), creatine phosphokinase isoenzyme (CK-MB), plasma brain natriuretic peptide (BNP), myocardial collagen volume fraction (CVF) and left ventricular mass index (LVWI) were measured. CK-MB levels in Ros-H and Ros-L rats were lower than in the diabetic group. Rosuvastatin alleviated myofibrosis cordis and fibroplastic proliferation. LVWI, BNP, CVF and TGF-beta1 mRNA and protein levels in the diabetic group were higher than in the control, but were reduced after rosuvastatin treatment. These results demonstrate that rosuvastatin dose-dependently reduces TGF-beta1 expression and inhibits the development of myocardial fibrosis in diabetic cardiomyopathy.

Topics: Animals; Body Weight; Cardiomyopathies; Collagen; Creatine Kinase; Diabetes Mellitus, Experimental; Diabetic Cardiomyopathies; Fibrosis; Fluorobenzenes; Glycated Hemoglobin; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertrophy, Left Ventricular; Male; Natriuretic Peptide, Brain; Pyrimidines; Rats; Rats, Wistar; Real-Time Polymerase Chain Reaction; Rosuvastatin Calcium; Sulfonamides; Transforming Growth Factor beta1

Achieving and maintaining optimal fluid status remains a major challenge in hemodialysis therapy. The aim of this interventional study was to assess the feasibility and clinical consequences of active fluid management guided by bioimpedance spectroscopy in chronic hemodialysis patients.. Fluid status was optimized prospectively in 55 chronic hemodialysis patients over 3 months (November 2011 to February 2012). Predialysis fluid overload was measured weekly using the Fresenius Body Composition Monitor. Time-averaged fluid overload was calculated as the average between pre- and postdialysis fluid overload. The study aimed to bring the time-averaged fluid overload of all patients into a target range of 0.5 ± 0.75 L within the first month and maintain optimal fluid status until study end. Postweight was adjusted weekly according to a predefined protocol.. Time-averaged fluid overload in the complete study cohort was 0.9 ± 1.6 L at baseline and 0.6 ± 1.1 L at study end. Time-averaged fluid overload decreased by -1.20 ± 1.32 L (P<0.01) in the fluid-overloaded group (n=17), remained unchanged in the normovolemic group (n=26, P=0.59), and increased by 0.59 ± 0.76 L (P=0.02) in the dehydrated group (n=12). Every 1 L change in fluid overload was accompanied by a 9.9 mmHg/L change in predialysis systolic BP (r=0.55, P<0.001). At study end, 76% of all patients were either on time-averaged fluid overload target or at least closer to target than at study start. The number of intradialytic symptoms did not change significantly in any of the subgroups.. Active fluid management guided by bioimpedance spectroscopy was associated with an improvement in overall fluid status and BP.

Topics: Aged; Blood Pressure; Blood Volume; Body Composition; Body Fluids; Body Weight; Dehydration; Dielectric Spectroscopy; Electric Impedance; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Quality of Life; Renal Dialysis; Renal Insufficiency, Chronic; Time Factors

Plasma NT-proBNP has previously been evaluated in dogs with degenerative mitral valve disease (DMVD). However, reference intervals (RI) established according to the Clinical Laboratory and Standards Institute (CLSI) recommendations have never been provided. The objectives of this prospective study were to assess effects of breed, body weight, age, and sex on plasma NT-proBNP, and to establish RI according to CLSI for this biomarker in a large population of dogs predisposed to DMVD. 183 Healthy small-sized dogs from 7 breeds were included. Assays were performed by ELISA. Effects of covariates were tested using a general linear model. Although a sex effect was demonstrated (P=0.01), no significant effect of breed, body weight or age was shown. The proposed RI was 157-2842 pmol/L. 7% of dogs had plasma NT-proBNP >2617 pmol/L, and were considered as outliers despite normal cardiovascular examination. In conclusion, plasma NT-proBNP may be high in a few healthy small-sized dogs.

Topics: Age Factors; Animals; Body Weight; Breeding; Dogs; Female; Male; Natriuretic Peptide, Brain; Peptide Fragments; Sex Factors; Species Specificity

The relationship between echocardiographically measured epicardial fat thickness (EFT) and plasma concentrations of leptin, ghrelin, and adiponectin has not been evaluated in patients with noncachectic heart failure (HF). Patients with noncachectic HF and age- and sex-matched controls did not differ significantly in EFT, whereas EFT values showed significant positive correlation with body mass index (BMI) in both groups and were negatively related with brain natriuretic peptide and positively with log leptin values in the HF group. In the control group, a positive correlation with high-sensitivity C-reactive protein (hsCRP) and a negative correlation with log ghrelin were found. In multivariable analysis, log leptin was a significant predictor of EFT in patients with HF, but this effect was not retained after adjusting for BMI. In contrast, log ghrelin and hsCRP were significant predictors of EFT in controls even after adjusting for BMI.

Topics: Adipose Tissue; Adiposity; Aged; Aged, 80 and over; Body Mass Index; Body Weight; C-Reactive Protein; Female; Ghrelin; Heart Failure; Homeostasis; Humans; Leptin; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Pericardium; Ultrasonography

We have previously shown that isoprenaline-induced cardiac hypertrophy causes significant changes in the expression of cytochromes P450 (CYP) and soluble epoxide hydrolase (sEH) genes. Therefore, it is important to examine whether the inhibition of sEH by 1-(1-methanesulfonyl-piperidin-4-yl)-3-(4-trifluoromethoxy-phenyl)-urea (TUPS) will protect against isoprenaline-induced cardiac hypertrophy.. Male Sprague-Dawley rats were treated with TUPS (0.65 mg kg(-1) day(-1), p.o.), isoprenaline (5 mg kg(-1) day(-1), i.p.) or the combination of both. In vitro H9c2 cells were treated with isoprenaline (100 μM) in the presence and absence of either TUPS (1 μM) or 11,12 EET (1 μM). The expression of hypertrophic, fibrotic markers and different CYP genes were determined by real-time PCR.. Isoprenaline significantly induced the hypertrophic, fibrotic markers as well as the heart to body weight ratio, which was significantly reversed by TUPS. Isoprenaline also caused an induction of CYP1A1, CYP1B1, CYP2B1, CYP2B2, CYP4A3 and CYP4F4 gene expression and TUPS significantly inhibited this isoprenaline-mediated effect. Moreover, isoprenaline significantly reduced 5,6-, 8,9-, 11,12- and 14,15-EET and increased their corresponding 8,9-, 11,12- and 14,15-dihydroxyeicosatrienoic acid (DHET) and the 20-HETE metabolites. TUPS abolished these isoprenaline-mediated changes in arachidonic acid (AA) metabolites. In H9c2 cells, isoprenaline caused a significant induction of ANP, BNP and EPHX2 mRNA levels. Both TUPS and 11,12-EET significantly decreased this isoprenaline-mediated induction of ANP, BNP and EPHX2.. TUPS partially protects against isoprenaline-induced cardiac hypertrophy, which confirms the role of sEH and CYP enzymes in the development of cardiac hypertrophy.

Topics: Animals; Atrial Natriuretic Factor; Body Weight; Cardiomegaly; Cardiotonic Agents; Cell Line; Cytochrome P-450 Enzyme System; Drug Antagonism; Epoxide Hydrolases; Gene Expression Regulation; Heart; Humans; Isoproterenol; Kidney; Liver; Natriuretic Peptide, Brain; Phenylurea Compounds; Piperidines; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction

This study was designed to investigate whether pretreatment of bone marrow mesenchymal stem cells (BMSCs) with 5-azacytidine (5-aza) or double intravenous infusion could enhance their therapeutic potential for dilated cardiomyopathy (DCM).. BMSCs were cultured for 2 weeks in the presence or absence of 5-aza and DCM serum. The cultured BMSCs (Groups 1 and 2), 5-aza-induced BMSCs (Groups 3 and 4), and medium alone (model control) were transplanted into 80 female Wistar rats by intravenous tail vein injection. Double infusion of BMSCs with 1-day time-interval was carried out in Groups 2 and 4. Postmortem histological analysis and evaluation of heart function were performed at 4 weeks post-transplantation.. Some transplanted BMSCs engrafted into myocardial tissue and were positive for cardiac marker troponin T. The hearts containing transplanted BMSCs secreted a larger amount of vascular endothelial growth factor. Cardiac function parameters and serum level of brain natriuretic peptide (BNP) did not differ among Groups 1, 3, and the model control. As compared with model control, BMSC transplantation in Groups 2 and 4 significantly decreased the serum level of BNP and improved cardiac contractile function, as evidenced by reduced left ventricular end-diastolic and end-systolic diameter, elevated ejection fraction, and fractional shortening.. BMSC transplantation is a promising strategy for the treatment of DCM. Pretreatment of BMSCs with 5-aza and DCM serum does not enhance their therapeutic efficacy, and the double intravenous BMSC infusion method is superior to single infusion for preserving cardiac contractile function in a rat model of DCM.

Topics: Animals; Azacitidine; Body Weight; Bone Marrow Cells; Bromodeoxyuridine; Cardiomyopathy, Dilated; Cell Transdifferentiation; Collagen; Female; Fibrosis; Gene Expression Regulation; Heart Function Tests; Infusions, Intravenous; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Myocardium; Natriuretic Peptide, Brain; Rats; Rats, Wistar; RNA, Messenger; Survival Analysis; Troponin T; Vascular Endothelial Growth Factor A

The relation between diabetes and stroke is bidirectional: diabetes is an important risk factor for ischemic stroke, and acute stroke frequently induces hyperglycemia. On the other hand, plasma B-type natriuretic peptide (BNP) levels are raised in diabetes and stroke. The purpose was to study how alloxan-induced diabetes might modify the effects of BNP in rabbit carotid arteries and the mechanisms involved in such actions. To do this, isometric tension in isolated rabbit carotid artery was recorded and prostanoids release and plasma NT-proBNP were measured by enzyme immunoassay. BNP induced a relaxation of phenylephrine-precontracted carotid arteries, and this relaxation was lower in diabetic than in control rabbits. Endothelium removal did not modify the relaxation to BNP in control rabbits but increased this relaxation in diabetic rabbits. In control rabbits, indomethacin inhibited the BNP-induced relaxation in the presence and in the absence of endothelium. In diabetic rabbits, indomethacin did not modify the BNP-induced relaxation in arteries with endothelium and inhibited it in arteries without endothelium. In the presence of BNP the carotid artery released thromboxane A2 and prostacyclin, and the release of endothelial prostacyclin was inhibited in diabetic rabbits. Glibenclamide and 4-aminopyridine inhibited the relaxation to BNP, and these inhibitions were lower in diabetic than in control rabbits. In conclusion, our results provide a new understanding concerning the mechanisms of the diabetes-induced hyporeactivity of the carotid artery to BNP, that at least include the loss of endothelial prostacyclin and a reduced participation of ATP-sensitive K(+) channels (KATP) and voltage-sensitive K(+) channels (KV).

Topics: Animals; Blood Glucose; Body Weight; Carotid Arteries; Diabetes Mellitus; Dose-Response Relationship, Drug; Epoprostenol; Male; Natriuretic Peptide, Brain; Nitric Oxide; Peptide Fragments; Potassium; Potassium Channels; Rabbits; Receptors, Atrial Natriuretic Factor

Chronic heart failure is often complicated by the development of cachexia with the loss of fat mass. Zinc α2-glycoprotein (ZAG) is a serum adipokine with lipolytic effects in cancer cachexia. We evaluated in patients with advanced heart failure with (CxHF) or without cachexia (nCxHF) the relationship of ZAG with circulating free fatty acid (FFA), as an index of lipolysis, and with other neurohormonal and inflammatory biomarkers. Two groups, nCxHF (n = 46) and CxHF (n = 18), the latter having a documented, involuntary, edema-free loss of body weight of at least 7.5% in the previous 6 months, underwent plasma determination of FFA, ZAG, norepinephrine (NE), tumor necrosis factor-α, and natriuretic peptide levels (atrial natriuretic, B-type natriuretic peptide). The patients were compared with age-matched healthy controls (CTR) (n = 21). Zinc α2-glycoprotein, atrial natriuretic peptide, B-type natriuretic peptide, and tumor necrosis factor-α circulating levels were similarly greater in CxHF and nCxHF than in CTR. Free fatty acid and NE were higher in CxHF than in nCxHF. A positive correlation between FFA and NE was found in both CxHF (r = 0.73, P < .01) and nCxHF (r = 0.48, P < .01) but only in CxHF between ZAG and FFA (r = 0.54, P = .02) and between ZAG and NE (r = 0.70, P < .01). No correlations between natriuretic peptides and ZAG were found. Serum ZAG levels are increased in advanced heart failure patients compared with CTR, without differences between CxHF and nCxHF. Only in CxHF, ZAG levels are directly correlated to circulating levels of FFA and NE, suggesting a close interaction of ZAG with sympathetic-mediated lipolysis.

Topics: Adipokines; Aged; Biomarkers; Body Weight; Cachexia; Case-Control Studies; Fatty Acids, Nonesterified; Female; Heart Failure; Humans; Inflammation; Lipolysis; Male; Natriuretic Peptide, Brain; Neurotransmitter Agents; Seminal Plasma Proteins; Tumor Necrosis Factor-alpha; Zn-Alpha-2-Glycoprotein

Losartan/hydrochlorothiazide (HCTZ) (Preminent®) is a fixed-dose combination of angiotensin II receptor blocker (ARB) and the thiazide diuretic HCTZ that has consistently been shown to be more effective than either losartan or HCTZ. Little is known about the relationship between losartan/HCTZ and blood levels of brain natriuretic peptide (BNP).. In this study, 44 patients with hypertension who were being treated with ARB were enrolled. The ARB was changed to losartan/HCTZ because of uncontrolled hypertension. Blood pressure (BP), pulse rate (PR), plasma levels of BNP and other biochemical parameters were analyzed at baseline and 6 and 12 months after the change from ARB. Of the total 44 patients, 33 (75%) achieved the target BP at 12 months. While there was no significant change in PR, systolic and diastolic BP were significantly reduced (-23 ± 3 mmHg and -10 ± 2 mmHg, respectively) during this period. Although there were no significant changes in biochemical parameters, plasma levels of BNP were significantly decreased, especially in patients who had higher levels of BNP at baseline, during this period.. Losartan/HCTZ therapy significantly reduced not only BP but also plasma levels of BNP in patients with hypertension. These findings suggest that losartan/HCTZ might have cardioprotective effects in patients with higher levels of BNP.

Topics: Aged; Blood Pressure; Body Weight; Diastole; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Heart Rate; Humans; Hydrochlorothiazide; Hypertension; Losartan; Male; Natriuretic Peptide, Brain; Systole

Plasma renin activity (PRA) is accepted as a marker for increased risk of cardiovascular diseases. However, the association between PRA and total mortality has not been fully explored in a general population. We here examined whether PRA is associated with increased total mortality in a general Japanese population. The participants of the Takahata study (3502 subjects; age, 62.5 ± 10.4 years), a population-based, longitudinal study of Japanese held from 2004 to 2006, were enrolled and followed up for up to 7 years. The incidence of death and causes of death were monitored annually to the end of 2010 (median follow-up, 2280 days). During the follow-up period, 143 subjects died. Kaplan-Meier analysis showed a significantly increased risk for total mortality in subjects with higher PRA (log-rank P < .001). Cox proportional hazard model analyses with adjustment for factors correlated with PRA (age, sex, weight, diastolic blood pressure, high-density lipoprotein cholesterol, uric acid, B-type natriuretic peptide, serum total protein, antihypertensive treatment, and diabetes) showed that higher PRA was associated with increased total mortality in linear regression models (per 1 increase in log 10 × PRA [nanograms per milliliter per hour]: hazard ratio, 2.12; 95% confidence interval, 1.47-3.06), between groups of patients stratified by quartiles of PRA (highest vs lowest quartile: 2.63, 1.57-4.41) and in subjects with high (≥ 2.0 ng/[mL h]) vs low (<2.0 ng/[mL h]) PRA (1.97, 1.37-2.83). Higher PRA was a significant and independent risk factor for increased total mortality in this Japanese population and may be a marker for subjects at an increased risk of total mortality.

Topics: Blood Pressure; Blood Proteins; Body Weight; Cholesterol; Cohort Studies; Cross-Sectional Studies; Female; Humans; Japan; Kaplan-Meier Estimate; Linear Models; Male; Middle Aged; Mortality; Natriuretic Peptide, Brain; Prospective Studies; Renin; Uric Acid

Endurance exercise may induce transient cardiac dysfunction. Data regarding the effect of caloric restriction on cardiac function is limited. We studied the effect of physical activity performed during extreme caloric deprivation on cardiac function.. Thirty-nine healthy male soldiers (mean age 20 ± 0.3 years) were studied during a field training exercise lasted 85-103 hours, with negligible food intake and unlimited water supply. Anthropometric measurements, echocardiographic examinations and blood and urine tests were performed before and after the training exercise.. Baseline VO(2) max was 59 ± 5.5 ml/kg/min. Participants' mean weight reduction was 5.7 ± 0.9 kg. There was an increase in plasma urea (11.6 ± 2.6 to 15.8 ± 3.8 mmol/L, p<0.001) and urine osmolarity (692 ± 212 to 1094 ± 140 mmol/kg, p<0.001) and a decrease in sodium levels (140.5 ± 1.0 to 136.6 ± 2.1 mmol/L, p<0.001) at the end of the study. Significant alterations in diastolic parameters included a decrease in mitral E wave (93.6 to 83.5 cm/s; p = 0.003), without change in E/A and E/E' ratios, and an increase in iso-volumic relaxation time (73.9 to 82.9 ms, p = 0.006). There was no change in left or right ventricular systolic function, or pulmonary arterial pressure. Brain natriuretic peptide (BNP) levels were significantly reduced post-training (median 9 to 0 pg/ml, p<0.001). There was no elevation in Troponin T or CRP levels. On multivariate analysis, BNP reduction correlated with sodium levels and weight reduction (R = 0.8, p<0.001).. Exposure to prolonged physical activity performed under caloric deprivation resulted in minor alterations of left ventricular diastolic function. BNP levels were significantly reduced due to negative water and sodium balance.

Topics: Adult; Biomarkers; Body Weight; Caloric Restriction; Echocardiography; Exercise; Heart; Humans; Israel; Male; Military Personnel; Natriuretic Peptide, Brain; Oxygen Consumption; Physical Education and Training; Ventricular Dysfunction, Left; Ventricular Dysfunction, Right

To determine the normal range of serum brain natriuretic peptide (BNP) in uncomplicated, singleton term pregnant patients.. Serum for analysis of BNP was drawn at admission to labor and delivery (= 104), prior to administration of intravenous fluid.. Median BNP was 20 pg/mL, with an interquartile range of 20 pg/mL (range 5-70 pg/mL; or a mean ± standard deviation [SD] of 23 ± 16 pg/mL). Brain natriuretic peptide negatively correlated with prepregnant (r = -.24, P < .05) and pregnant weight (r = -26, P < .01) and with heart rate (r = -.35, P < 0.001); heart rate was also positively correlated with BMI (r = .32). Brain natriuretic peptide levels were higher in Hispanic than African American women, independent of body mass index (BMI) and heart rate.. Brain natriuretic peptide values found in term pregnant patients are similar to those of prepregnant women of reproductive age. Brain natriuretic peptide levels appear to be set by conditions present in the prepregnant condition and maintained, despite changes in plasma volume, systemic vascular resistance, and cardiac output.

Topics: Adolescent; Adult; Asian; Black or African American; Body Mass Index; Body Weight; Female; Heart Rate; Hispanic or Latino; Humans; Labor, Obstetric; Natriuretic Peptide, Brain; Pregnancy; Reference Values; White People

To identify cardiac mechanisms that contribute to adaptation to high altitudes in Tibetan antelope (Pantholops hodgsonii).. 9 male Tibetan antelope and 10 male Tibetan sheep (Ovis aries).. Tibetan antelope and Tibetan sheep inhabiting a region with an altitude of 4,300 m were captured, and several cardiac variables were measured. Expression of genes for atrial natriuretic peptide, brain natriuretic peptide, and calcium-calmodulin-dependent protein kinase II δ was measured via real-time PCR assay.. Ratios of heart weight to body weight for Tibetan antelope were significantly greater than those of Tibetan sheep, but ratios of right-left ventricular weights were similar. Mean ± SD baseline heart rate (26.33 ± 6.15 beats/min) and systolic arterial blood pressure (97.75 ± 9.56 mm Hg) of antelope were significantly lower than those of sheep (34.20 ± 6.57 beats/min and 130.06 ± 17.79 mm Hg, respectively). The maximum rate of rise in ventricular pressure in antelope was similar to that in Tibetan sheep, but after exposure to air providing a fraction of inspired oxygen of 14.6% or 12.5% (ie, hypoxic conditions), the maximum rate of rise in ventricular pressure of the antelope increased significantly to 145.1% or 148.1%, respectively, whereas that of the sheep decreased to 68.4% or 70.5%, respectively. Gene expression of calcium-calmodulin-dependent protein kinase II δ and atrial natriuretic peptide, but not brain natriuretic peptide, in the left ventricle of the heart was significantly higher in antelope than in sheep.. Hearts of the Tibetan antelope in this study were well adapted to high-altitude hypoxia as shown by higher heart weight ratios, cardiac contractility in hypoxic conditions, and expression of key genes regulating cardiac contractility and cardiac hypertrophy, compared with values for Tibetan sheep.

Topics: Adaptation, Biological; Altitude; Animals; Antelopes; Atrial Natriuretic Factor; Blood Cell Count; Body Weight; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Heart; Hemoglobins; Male; Natriuretic Peptide, Brain; Organ Size; Real-Time Polymerase Chain Reaction; Sheep; Tibet; Ventricular Pressure

B-type natriuretic peptide (BNP) is a biomarker of cardiovascular disease that is common in adults with chronic kidney disease (CKD). However, in children with CKD, the range and predictive power of BNP concentrations are not known. We aimed to determine the effect of HD on BNP, as well as the prognostic impact of BNP, in end-stage renal disease (ESRD) children undergoing hemodialysis (HD). Thirty-five children with chronic renal failure (16 boys age 12.1 ± 3.7 years) on maintenance HD were included. BNP level was measured, and Doppler echocardiography was performed 30 min before (pre-HD BNP) and 30 min after (post-HD BNP) HD in each patient. An adverse event was defined as all-cause death and heart failure hospitalization. The median pre-HD BNP, the post-HD BNP, and the change in BNP were, respectively, 240 pg/ml (72 to 3346), 318 pg/ml (79 to 3788), and 9 pg/ml (-442 to 1889). Pre-HD BNP concentration was negatively correlated with left ventricular (LV) ejection fraction (r = -0.41, P = 0.018). During a mean follow-up of 39 ± 14 months, 6 patients died, and 3 were hospitalized for heart failure. Using univariate analysis, BNP before and after HD as well as Doppler tissue imaging velocities had a strong graded relationship with adverse events. Cox proportional hazards model demonstrated that pre-HD body weight (P = 0.008), pre-HD BNP (P = 0.011), and post-HD BNP (P = 0.038) remained independent predictors of adverse outcome. Even in case of ESRD, BNP still strongly correlated with LV systolic and diastolic dysfunction and was associated with mortality in HD children.

Topics: Adolescent; Biomarkers; Body Weight; Cause of Death; Child; Child, Preschool; Cohort Studies; Echocardiography, Doppler; Female; Follow-Up Studies; Humans; Kidney Failure, Chronic; Male; Natriuretic Peptide, Brain; Predictive Value of Tests; Prospective Studies; Renal Dialysis; Stroke Volume; Ventricular Dysfunction, Left; Young Adult

Myocardial interstitial fibrosis causes left ventricular stiffness and diastolic dysfunction. Despite its clinical significance, treatment options are limited. The flavonoid baicalein, extracted from roots of a Chinese medicinal plant, Scutellaria baicalensis Georgi was shown to inhibit liver fibrosis. This study sought to investigate whether chronic treatment with baicalein could attenuate myocardial fibrosis in spontaneously hypertensive rats (SHR). SHR were treated daily with baicalein while the control group received vehicle. At the end of study, SHR control group developed significant myocardial fibrosis that was attenuated by baicalein treatment for 4 and 12 weeks. Rats treated with baicalein were protected against an increase in heart to body weight ratio, plasma level of brain natriuretic peptides, intraventricular septum thickness, myocardial collagen volume of left ventricle (all P<0.05, respectively). The antifibrotic effects of baicalein were further illustrated by the suppressed expression of left ventricle pro-collagens I and III accompanied by the decreased expression of 12-lipoxygenase, and by reduced expression and activity of matrix metallopeptidase 9 and extracellular signal-regulated kinases. The present results show for the first time that baicalein can inhibit cardiac fibrosis in hypertensive rats.

Topics: Animals; Arachidonate 12-Lipoxygenase; Blood Pressure; Body Weight; Collagen Type I; Collagen Type III; Extracellular Signal-Regulated MAP Kinases; Fibrosis; Flavanones; Gene Expression Regulation; Heart Ventricles; Male; Matrix Metalloproteinase 9; Myocardium; Natriuretic Peptide, Brain; Organ Size; Phosphoproteins; Procollagen; Rats; Rats, Inbred SHR; RNA, Messenger; Ventricular Septum

The cardiac nitric oxide and endothelin-1 (ET-1) systems are closely linked and play a critical role in cardiac physiology. The balance between both systems is often disturbed in cardiovascular diseases. To define the cardiac effect of excessive ET-1 in a status of nitric oxide deficiency, we compared left ventricular function and morphology in wild-type mice, ET-1 transgenic (ET(+/+)) mice, endothelial nitric oxide synthase knockout (eNOS(-/-)) mice, and ET(+/+)eNOS(-/-) mice.. eNOS(-/-) and ET(+/+)eNOS(-/-) mice developed high blood pressure compared with wild-type and ET(+/+) mice. Left ventricular catheterization showed that eNOS(-/-) mice, but not ET(+/+)eNOS(-/-) , developed diastolic dysfunction characterized by increased end-diastolic pressure and relaxation constant tau. To elucidate the causal molecular mechanisms driving the rescue of diastolic function in ET(+/+)eNOS(-/-) mice, the cardiac proteome was analyzed. Two-dimensional gel electrophoresis coupled to mass spectrometry offers an appropriate hypothesis-free approach. ET-1 overexpression on an eNOS(-/-) background led to an elevated abundance and change in posttranslational state of antioxidant enzymes (e.g., peroxiredoxin-6, glutathione S-transferase mu 2, and heat shock protein beta 7). In contrast to ET(+/+)eNOS(-/-) mice, eNOS(-/-) mice showed an elevated abundance of proteins responsible for sarcomere disassembly (e.g., cofilin-1 and cofilin-2). In ET(+/+)eNOS(-/-) mice, glycolysis was favored at the expense of fatty acid oxidation.. eNOS(-/-) mice developed diastolic dysfunction; this was rescued by ET-1 transgenic overexpression. This study furthermore suggests that cardiac ET-1 overexpression in case of eNOS deficiency causes specifically the regulation of proteins playing a role in oxidative stress, myocytes contractility, and energy metabolism.

Topics: Animals; Blood Pressure; Blotting, Western; Body Weight; Diastole; Endothelin-1; Female; Immunohistochemistry; Male; Mice; Mice, Knockout; Mice, Transgenic; Natriuretic Peptide, Brain; Nitric Oxide Synthase Type III; Organ Size; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry

To evaluate the diagnostic value of plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations in Doberman Pinschers in various stages of dilated cardiomyopathy (DCM).. 328 Doberman Pinschers.. Staging of DCM was determined via analysis of results of physical examinations, 24-hour ambulatory ECG (Holter) recordings, and echocardiographic evaluations. Plasma samples for NT-proBNP assays were obtained at each examination. Concentrations of NT-proBNP were measured in 337 samples obtained from 196 healthy Doberman Pinschers (control dogs) and in 195 samples obtained from 132 Doberman Pinschers in various stages of DCM. These included dogs that had ventricular premature contractions (VPCs; 79 samples), echocardiographic changes (23 samples), or both (51 samples); 16 samples were from dogs with overt DCM, and 26 were from dogs that were considered normal during initial examination but developed DCM within 1.5 years after this assessment. Receiver operating characteristic curves were analyzed to determine sensitivity and specificity of NT-proBNP concentrations for detection of DCM.. NT-proBNP concentrations in dogs that had or developed DCM were significantly higher than those of control dogs. Sensitivity and specificity of NT-proBNP concentrations (cutoff value, > 400 pmol/L) to detect all stages of DCM were 81.1 % and 75.0%, respectively; sensitivity was 90.0% and specificity was 75.0% to predict echocardiographic changes. Specificity to detect echocardiographic changes was 90.4% at a cutoff value of 550 pmol/L.. Plasma concentrations of NT-proBNP were increased in dogs with DCM and in apparently healthy dogs that developed DCM within 1.5 years after samples were obtained, compared with concentrations in control dogs.

Topics: Age Distribution; Animal Husbandry; Animals; Biomarkers; Body Weight; Cardiomyopathy, Dilated; Dog Diseases; Dogs; Echocardiography; Female; Male; Natriuretic Peptide, Brain; Pedigree; Peptide Fragments; ROC Curve; Sensitivity and Specificity; Sex Distribution

The objective of this study was to establish the potential utility of N-terminal pro-brain natriuretic peptide (NT-proBNP) in the management of patent ductus arteriosus (PDA). This was a monocentric prospective blind study that was conducted in a referral neonatal intensive care unit. The patients were very low-birth-weight/gestational-age neonates. Babies with cardiac congenital anomaly other than PDA, life-threatening congenital malformation, severe asphyxia at birth, persistent pulmonary hypertension, and death within the first week of life were excluded. Plasma NT-proBNP concentrations were determined on days 2, 4, and 7 of life. Echocardiography was performed on days 4 and 7. Results were blinded to clinicians. Only echographic results were available upon request. Thirty-one infants were included. NT-proBNP levels were significantly correlated to ductal size and to left atrial-to-aortic diameter ratio. The median NT-proBNP on both days 2 and 4 was significantly higher in neonates with later treated or persistent PDA. A level above 10.000 pg/mL at 48 h of age yielded a 100% positive and a 87% negative predictive value to exclude spontaneous ductal closure. However, no NT-proBNP threshold could predict which PDA would be judged necessary to treat. It was concluded that early low NT-proBNP values can be used as a reliable independent marker to predict spontaneous ductal closure in preterm neonates. Yet, high NT-proBNP levels should not be used to guide the decision to treat PDA, the risk being of treating many bystanding PDAs.

Topics: Body Weight; Ductus Arteriosus, Patent; Early Diagnosis; Echocardiography; Follow-Up Studies; Humans; Infant, Newborn; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Premature Birth; Prognosis; Prospective Studies; Protein Precursors; Remission, Spontaneous; ROC Curve; Severity of Illness Index; Time Factors

Increased plasma amino-terminal-cleavage-fragment of NP (NT-proBNP) is an established indicator for heart failure. Moreover, obese adults had low circulating NT-proBNP suggesting an obesity-related dysregulation (natriuretic handicap). Secretion and/or clearance of NT-proBNP were discussed to be impaired in obesity. As only older adults were investigated so far, it remains unclear when during the evolution of obesity the state of a natriuretic handicap develops, and whether NT-proBNP may still serve as a relevant cardiac marker in obese juveniles.. We analysed NT-proBNP in juvenile (n=274, 10-18 years) and middle-aged (n=277, 18-50 years) normal weight (n=213) and obese (n=338) probands together with complex anthropometry, carotis sonography, clinical, and laboratory parameters.. NT-proBNP showed a significant gender and age interaction. Adult females had significant higher NT-proBNP than adult males, and higher levels than juvenile females. Adult males had lower levels than juvenile males. Only a weak age and weight interaction was seen with obese juveniles which showed higher NT-proBNP than obese adults. Moreover, normal weight probands had higher NT-proBNP than overweight and obese. In a multiple regression including all probands, gender, creatinine and uric acid were the best predictors for NT-proBNP. In adults, female gender is the strongest driver for increased NT-proBNP.. These results argue against an essential influence of obesity to B-type cardiac natriuretic hormone system regulation in the absence of heart failure, and suggest NT-proBNP as a useful cardiac marker irrespective of age and obesity.

Topics: Adolescent; Adult; Body Weight; Child; Disease Progression; Family; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Regression Analysis; Young Adult

Topics: Age Factors; Blood Pressure; Body Weight; Cardiology; Clinical Trials as Topic; Edema; Heart Failure; Humans; Natriuretic Peptide, Brain; Research Design; Treatment Outcome

We investigated cardiac hypertrophy elicited by rosiglitazone treatment at the level of protein synthesis/degradation, mTOR, MAPK and AMPK signalling pathways, cardiac function and aspects of carbohydrate/lipid metabolism. Hearts of rats treated or not with rosiglitazone (15 mg/kg day) for 21 days were evaluated for gene expression, protein synthesis, proteasome and calpain activities, signalling pathways, and function by echocardiography. Rosiglitazone induced eccentric heart hypertrophy associated with increased expression of ANP, BNP, collagen I and III and fibronectin, reduced heart rate and increased stroke volume. Rosiglitazone robustly increased heart glycogen content ( approximately 400%), an effect associated with increases in glycogenin and UDPG-PPL mRNA levels and glucose uptake, and a reduction in glycogen phosphorylase expression and activity. Cardiac triglyceride content, lipoprotein lipase activity and mRNA levels of enzymes involved in fatty acid oxidation were also reduced by the agonist. Rosiglitazone-induced cardiac hypertrophy was associated with an increase in myofibrillar protein content and turnover (increased synthesis and an enhancement of calpain-mediated myofibrillar degradation). In contrast, 26S beta5 chymotryptic proteasome activity and mRNA levels of 20S beta2 and beta5 and 19S RPN 2 proteasome subunits along with the ubiquitin ligases atrogin and CHIP were all reduced by rosiglitazone. These morphological and biochemical changes were associated with marked activation of the key growth-promoting mTOR signalling pathway, whose pharmacological inhibition with rapamycin completely blocked cardiac hypertrophy induced by rosiglitazone. The study demonstrates that both arms of protein balance are involved in rosiglitazone-induced cardiac hypertrophy, and establishes the mTOR pathway as a novel important mediator therein.

Topics: Animals; Atrial Natriuretic Factor; Blotting, Western; Body Weight; Cardiomegaly; Eating; Echocardiography; Glucosyltransferases; Glycogen; Glycogen Phosphorylase; Glycogen Synthase; Glycoproteins; Hemodynamics; Hypoglycemic Agents; Lipoprotein Lipase; Male; Myofibrils; Natriuretic Peptide, Brain; Proteasome Endopeptidase Complex; Protein Kinases; Rats; Rats, Sprague-Dawley; Rosiglitazone; Thiazolidinediones; TOR Serine-Threonine Kinases; UTP-Glucose-1-Phosphate Uridylyltransferase

Left ventricular (LV) hypertrophy (LVH) is an independent risk factor for cardiovascular mortality and is commonly caused by hypertension. In rodents, transverse aortic constriction (TAC) is a model regularly employed in mechanistic studies of the response of the LV to pressure overload. We previously reported that inbred strains of male mice manifest different cardiac responses to TAC, with C57BL/6J (B6) developing LV dilatation and impaired contractility and 129S1/SvImJ (129) males displaying concentric LVH. In the present study, we investigated sex and parent-of-origin effects on the response to TAC by comparing cardiac function, organ weights, expression of cardiac hypertrophy markers, and histology in female B6 and female 129 mice and in F1 progeny of reciprocal crosses between B6 and 129 mice (B6129F1 and 129B6F1). Five weeks after TAC, heart weight increased to the greatest extent in 129B6F1 mice and the least extent in 129 and B6129F1 mice. Female 129B6F1 and B6 mice were relatively protected from the increase in heart weight that occurs in their male counterparts with pressure overload. The response to TAC in 129 consomic mice bearing the B6 Y chromosome resembled that of 129 rather than 129B6F1 mice, indicating that the B6 Y chromosome does not account for the differences in the reciprocal cross. Our results suggest that susceptibility to LVH is more complex than simple Mendelian inheritance and that parental origin effects strongly impact the LV response to TAC in these commonly used inbred strains.

Topics: Animals; Aortic Diseases; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Disease Models, Animal; Epigenesis, Genetic; Female; Fibrosis; Genes, Y-Linked; Hypertrophy, Left Ventricular; Male; Mice; Mice, Inbred C57BL; Myosin Heavy Chains; Natriuretic Peptide, Brain; Organ Size; Sex Factors; Species Specificity

Whether a high plasma aldosterone concentration induced by strict salt restriction promotes cardiac remodeling remains controversial. Male Sprague-Dawley rats at 10weeks of age were given normal salt (NS) (1.5% NaCl) or low salt (LS) (0.05% NaCl) diets. Each animal underwent aortocaval fistula creation for volume-overloaded heart failure or sham surgery. All rats with a fistula received either vehicle or a non-hypotensive dose of spironolactone (200mg/kg/day) by gavage. Two weeks later, the LS diet significantly increased the plasma aldosterone level in the sham-operated and fistula-created rats (2677+/-662pg/ml and 2406+/-422pg/ml) compared with that in rats given the NS diet (518+/-18pg/ml and 362+/-45pg/ml, respectively). In sham-operated rats, the difference in plasma aldosterone level did not affect the extent of myocardial fibrosis (1.8+/-0.1% with LS diet vs. 1.5+/-0.3% with NS diet). However, the increase in myocardial fibrosis in fistula-created rats was more prominent with the LS diet than with the NS diet (4.7+/-0.3% vs. 3.4+/-0.1%). In addition, the fistula-created rats on the LS diet expressed significantly increased oxidative stress and transforming growth factor-beta compared with those on the NS diets (P<0.05). These increases in the fistula-created rats on the LS diet were significantly suppressed by the non-hypotensive dose of spironolactone (P<0.05). These results suggest that increased plasma aldosterone level with strict salt restriction activated the mineralocorticoid receptor signaling in volume-overloaded condition, resulting in increased myocardial fibrosis.

Topics: Aldosterone; Animals; Atrial Natriuretic Factor; Body Weight; Cell Size; Contraindications; Diet, Sodium-Restricted; Endomyocardial Fibrosis; Heart; Heart Failure; Hemodynamics; Hypertension; Male; Mineralocorticoid Receptor Antagonists; Myocardium; Myocytes, Cardiac; Natriuretic Peptide, Brain; Organ Size; Rats; Rats, Sprague-Dawley; Receptors, Mineralocorticoid; Signal Transduction; Spironolactone; Transforming Growth Factor beta; Tyrosine; Ventricular Remodeling

The aim of the study was to analyze the influence of body weight of the adult heart recipient on the chance to obtain a transplant.. We analyzed the data from all 658 patients listed for heart transplantation.. During the follow-up period, 325 (49%) of listed patients underwent transplantation with 102 (15%) succumbing before heart transplantation. The mean weight of transplanted patients was 73.7 +/- 13.7 kg and 81.2 +/- 15.4 kg for those not transplanted (P < .00001). Patients were divided according to body weight in two groups: light = below 80 kg (n = 360) or heavy > or = 80 kg or above (n = 297). On the transplant list, 111 heavy patients (37%) versus 213 light patients (59%) underwent the procedure, a significant difference. The waiting time among light patients was 255 versus heavy patients of 395 days (P < .005). There was a similar number of deaths before transplantation among the light (n = 56 360 patients; 15.5%) versus the heavy group (49/297; 16%). Upon multivariate Cox mode analysis independent factors related to not receiving a heart transplant were greater weight, systolic blood pressure, pulmonary vascular resistance, Heart Failure Survival Score (HFSS) score and lower N-terminal pro-brain natriuretic peptide (NTproBNP) levels.. Among adult heart transplant candidates, the chance to receive a heart transplant significantly decreased when the recipient's weight exceeded 80 kg. Patients with a body weight more than 110 kg had a poor chance to receive a heart transplantation.

Topics: Adult; Blood Pressure; Body Height; Body Weight; Diastole; Heart Failure; Heart Rate; Heart Transplantation; Humans; Middle Aged; Natriuretic Peptide, Brain; Overweight; Peptide Fragments; Poland; Probability; Registries; Survival Rate; Survivors; Thinness; Vascular Resistance; Ventricular Function, Left

Topics: Atrial Natriuretic Factor; Body Weight; Cyclic GMP; Diabetes Mellitus; Dietary Fats; Energy Metabolism; Homeostasis; Humans; Lipid Peroxidation; Mitochondria; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Natriuretic Peptides; Signal Transduction

Diminished constriction of arteries and veins following exposure to microgravity or bed rest is associated with a reduced ability to augment peripheral vascular resistance (PVR) and stroke volume during orthostasis. We tested the hypothesis that small mesenteric arteries and veins, which are not exposed to large pressure shifts during simulated microgravity via head-down tail suspension (HDT), will exhibit decrements in adrenergic constriction after HDT in rats. Small mesenteric arteries and veins from control (Con; n = 41) and HDT (n = 35) male Sprague-Dawley rats were studied in vitro. Vasoactive responsiveness to norepinephrine (NE) in arteries (10(-9) to 10(-4) M) and veins (pressure-diameter responses from 2 to 12 cmH(2)O after incubation in 10(-6) or 10(-4) M NE) were evaluated. Plasma concentrations of atrial (ANP) and NH(2)-terminal prohormone brain (NT-proBNP) natriuretic peptides were also measured. In mesenteric arteries, sensitivity and maximal responsiveness to NE were reduced with HDT. In mesenteric veins there was a diminished venoconstriction to NE at any given pressure in HDT. Plasma concentrations of both ANP and NT-proBNP were increased with HDT, and maximal arterial and venous constrictor responses to NE after incubation with 10(-7) M ANP or brain natriuretic peptide (BNP) were diminished. These data demonstrate that, in a vascular bed not subjected to large hydrodynamic differences with HDT, both small arteries and veins have a reduced responsiveness to adrenergic stimulation. Elevated levels of circulating ANP or NT-proBNP could adversely affect the ability of these vascular beds to constrict in vivo and conceivably could alter the intrinsic constrictor properties of these vessels with long-term exposure.

Topics: Animals; Atrial Natriuretic Factor; Body Weight; Capillaries; Head-Down Tilt; Male; Mesenteric Arteries; Mesenteric Veins; Muscle, Smooth, Vascular; Natriuretic Peptide, Brain; Norepinephrine; Organ Size; Rats; Rats, Sprague-Dawley; Splanchnic Circulation; Stimulation, Chemical; Sympathetic Nervous System; Vascular Resistance; Vasoconstriction; Vasoconstrictor Agents; Weightlessness Simulation

Although B-type natriuretic peptide (BNP) levels correlate with volume overload in congestive heart failure, its usefulness in patients with renal dysfunction has been questioned. A simple test to estimate volume overload and assist in the management of dry weight in hemodialysis (HD) patients would be useful.. Thirty-nine patients--aged 64 +/- 2 years (mean +/- SEM), male-female ratio of 37:2--undergoing HD thrice weekly for at least 30 days were studied. Samples were collected at the start and end of each of 3 consecutive HD sessions. Pre- and postsession weights and blood pressures were recorded. Left ventricular ejection fractions were obtained from echocardiograms performed within 1 year of enrollment. The first session was the dialysis session after a 72-hour interdialytic period, whereas the second and third sessions were after a 48-hour period. Plasma volume changes were measured in a subset of 13 patients.. Pre- and postdialysis BNP levels for each of the 3 sessions were 434 and 343 pg/mL, 347 and 231 pg/mL, and 249 and 202 pg/mL, respectively. The values for body weights were 82.6 +/- 3.6 and 78.6 +/- 3.5 kg, 81.5 +/- 3.6 and 78.2 +/- 3.5 kg, and 81.5 +/- 3.46 and 78.3 +/- 3.5 kg, respectively. The values of mean systolic blood pressures were 150 +/- 4 and 134 +/- 3 mm Hg, 142 +/- 4 and 134 +/- 4 mm Hg, and 142 +/- 4 and 131 +/- 4 mm Hg, respectively. The values for mean diastolic blood pressures were 81 +/- 2.5 and 70 +/- 2.4 mm Hg, 74 +/- 2.4 and 72.1 +/- 2.2 mm Hg, and 76 +/- 2.9 and 72 +/- 2.9 mm Hg, respectively. There was no correlation between changes in intradialytic BNP values and other measured parameters. Plasma volume changed minimally during dialysis.. Values of BNP are elevated in patients with end-stage renal disease and decline after each dialysis session. Over the course of a week, BNP levels gradually declined irrespective of changes in weight or blood pressure. The lack of correlation between changes in BNP and changes in measured clinical parameters is partly explained by a lack of a significant change in plasma volume. The highest BNP values were seen in patients with systolic dysfunction.

Topics: Blood Volume; Body Weight; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Renal Dialysis

The transcription factors involved in the activation of cardiac gene expression by angiotensin II (Ang II) in vivo are not well understood. Here we studied the contribution of transcriptional elements to the activation of the cardiac B-type natriuretic peptide (BNP) gene promoter by Ang II in conscious rats and in angiotensin II type 1 receptor (AT1R) transgenic mice. Rat BNP luciferase reporter gene constructs were injected into the left ventricular wall. The mean luciferase activity was 1.8-fold higher (P<0.05) in the ventricles of animals subjected to 2-week Ang II infusion as compared with vehicle infusion. Our results indicate that GATA binding sites at -90 and -81 in the rat BNP promoter are essential for the in vivo response to Ang II. The GATA factor binding to these sites is GATA-4. BNP mRNA levels and GATA-4 binding activity are also increased in the hypertrophied hearts of aged AT1R transgenic mice.

Topics: Angiotensin II; Animals; Body Weight; Cells, Cultured; DNA; GATA4 Transcription Factor; GATA6 Transcription Factor; Gene Expression Regulation; Hypertension; Hypertrophy, Left Ventricular; Male; Mice; Mice, Transgenic; Myocardium; Natriuretic Peptide, Brain; Organ Size; Promoter Regions, Genetic; Protein Binding; Proto-Oncogene Proteins c-ets; Rats; Rats, Sprague-Dawley; Receptor, Angiotensin, Type 1; RNA, Messenger; Transcription Factor AP-1; Transcriptional Activation

Topics: Blood Volume; Body Weight; Female; Humans; Kidney Failure, Chronic; Male; Natriuretic Peptide, Brain; Renal Dialysis

This study determined whether exercise training prevents pathological hypertrophy in the left ventricle by modulation of myocardial and apoptosis-associated genes. We used spontaneously hypertensive rats (n=15, non-exercise SHR), exercise-trained SHR (n=15, treadmill exercise for 12 weeks), and sedentary Wistar-Kyoto (WKY) rats (n=15). Exercise-trained SHR expressed adaptive changes such as reduced body weight, heart rate, blood pressures, left ventricle wall thickness, lipid profiles, and homocysteine level. The mRNA expression of angiotensin converting enzyme, endothelin-1, and brain natriuretic peptides in the heart was lower in the exercise-trained SHR and in the WKY than in the non-exercise SHR, whereas mRNA expression of caveolin-3 and eNOS in the heart was higher. Bcl-2 protein was higher in the exercise-trained SHR than in the WKY and the non-exercise SHR. In contrast, Bax protein levels were lower in the exercise-trained SHR and in the WKY than in the non-exercise SHR. Furthermore, the levels of the active forms of caspase-3 (20 kDa) were lower in the exercise-trained SHR and in the WKY than in the non-exercise SHR. These findings suggest that exercise training prevents pathological hypertrophy in the left ventricle by modulation of myocardial genes and that it interferes with a signal transduction pathway of apoptosis secondary to the pathological cardiac hypertrophy.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Blood Pressure; Body Weight; Cardiomegaly; Caspase 3; Caspases; Caveolin 3; Endothelin-1; Gene Expression; Heart Rate; Homocysteine; Lipids; Male; Myosin Heavy Chains; Natriuretic Peptide, Brain; Nitric Oxide Synthase Type III; Peptidyl-Dipeptidase A; Physical Conditioning, Animal; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Inbred SHR; Rats, Inbred WKY; RNA, Messenger

High levels of microphthalmia transcription factor (MITF) expression have been described in several cell types, including melanocytes, mast cells, and osteoclasts. MITF plays a pivotal role in the regulation of specific genes in these cells. Although its mRNA has been found to be present in relatively high levels in the heart, its cardiac role has never been explored. Here we show that a specific heart isoform of MITF is expressed in cardiomyocytes and can be induced by beta-adrenergic stimulation but not by paired box gene 3 (PAX3), the regulator of the melanocyte MITF isoform. In 2 mouse strains with different MITF mutations, heart weight/body weight ratio was decreased as was the hypertrophic response to beta-adrenergic stimulation. These mice also demonstrated a tendency to sudden death following beta-adrenergic stimulation. Most impressively, 15-month-old MITF-mutated mice had greatly decreased heart weight/body weight ratio, systolic function, and cardiac output. In contrast with normal mice, in the MITF-mutated mice, beta-adrenergic stimulation failed to induce B-type natriuretic peptide (BNP), an important modulator of cardiac hypertrophy, while atrial natriuretic peptide levels and phosphorylated Akt were increased, suggesting a cardiac stress response. In addition, cardiomyocytes cultured with siRNA against MITF showed a substantial decrease in BNP promoter activity. Thus, for what we believe is the first time, we have demonstrated that MITF plays an essential role in beta-adrenergic-induced cardiac hypertrophy.

Topics: Animals; Body Weight; Cardiomegaly; Cell Enlargement; Cell Line; Extracellular Signal-Regulated MAP Kinases; Gene Expression; Heart; Isoproterenol; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Mutant Strains; Microphthalmia-Associated Transcription Factor; Models, Biological; Mutation; Myocardium; Myocytes, Cardiac; Natriuretic Peptide, Brain; NIH 3T3 Cells; Organ Size; Paired Box Transcription Factors; PAX3 Transcription Factor; Phosphorylation; Proto-Oncogene Proteins c-akt; RNA, Small Interfering

The streptozotocin (STZ)-treated rat is a widely studied experimental model of diabetes mellitus (DM). Its pathophysiology includes hypoinsulinemia, hyperglycemia, cardiac hypertrophy, and a cardiomyopathy that is characterized by the presence of diastolic and/or systolic contractile dysfunction. As part of their endocrine function cardiomyocytes in the heart produce and secrete a family of related peptide hormones called the natriuretic peptides that include A-type natriuretic peptide (ANP) and B-type natriuretic peptide (BNP). ANP and BNP levels are variously augmented in patients with hypertension, cardiac overload, in the ventricles of failing or hypertrophied heart, in cardiac heart failure, in acute myocardial infarction (MI), and in some circumstances in DM. In this article, the effects of BNP on ventricular myocyte contraction and Ca2+ transport in STZ-induced diabetic rats have been investigated. BNP concentration was significantly increased in blood plasma and in atrial muscle in STZ-induced diabetic rats compared to age-matched controls. BNP was 11.9 +/- 0.9 ng/mL in plasma from diabetic rats compared to 6.7 +/- 1.6 ng/mL in controls and 15.8 +/- 2.0 ng/mg protein in diabetic atrial muscle compared to 8.5 +/- 1.0 ng/mg protein in controls. The heart weight to body weight ratio, an indicator of hypertrophy, was significantly increased in diabetic rat heart (4.3 +/- 0.1 mg/g) compared to controls (3.7 +/- 0.04 mg/g). The amplitude of shortening was not significantly altered in diabetic myocytes (10.3 +/- 0.4%) compared to controls (10.9 +/- 0.4%). BNP reduced the amplitude of shortening to a greater extent in diabetic myocytes (8.1 +/- 0.6%) compared to controls (10.1 +/- 0.4%). The time to peak (TPK) shortening was significantly prolonged in diabetic myocytes (254 +/- 8 ms) compared to controls (212 +/- 5 ms) and was not additionally altered by BNP. The time to half relaxation of shortening was also significantly prolonged in diabetic myocytes (131 +/- 8 ms) compared to controls (111 +/- 5 ms). BNP (10(-8) to 10(-6) M) normalized the time to half relaxation of shortening in diabetic myocytes to that of controls. Time to peak (TPK) shortening of Ca2+ was not different between diabetic and control rats. However, BNP (10(-7) M) increases TPK of Ca2+ significantly. The amplitude of the Ca2+ transient was significantly increased in diabetic myocytes (0.42 +/- 0.02 Ratio units [RU]) compared to controls (0.36 +/- 0.02 RU) and was not additionally alte

Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Heart Ventricles; Muscle Cells; Myocardial Contraction; Natriuretic Peptide, Brain; Organ Size; Rats; Ventricular Function

Hepatitis C virus (HCV) has been reported to be associated with cardiomyopathy. However, the mechanism of cardiomyopathy in chronic HCV infection is still unclear. Therefore, we investigate the development of cardiomyopathy in mice transgenic for the HCV-core gene. After the age of 12 months, mice developed cardiomyopathy that appeared as left ventricular dilatation, and systolic and diastolic dysfunction assessed by Doppler echocardiography. Histologically, hypertrophy of cardiomyocytes, cardiac fibrosis, disarray and scarcity of myofibrils, vacuolization and deformity of nuclei, myofibrillar lysis, streaming of Z-bands, and an increased number of bizarre-shaped mitochondria were found in HCV-core transgenic mice. These histological changes are just consistent with cardiomyopathy. In conclusion, the HCV-core protein directly plays an important role in the development of cardiomyopathy.

Topics: Actin Cytoskeleton; Animals; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Echocardiography, Doppler; Fibrosis; Gene Expression Regulation, Viral; Hepacivirus; Hepatitis C; Hypertrophy, Left Ventricular; Male; Mice; Mice, Transgenic; Mitochondria, Heart; Myocarditis; Myocardium; Myocytes, Cardiac; Natriuretic Peptide, Brain; NF-kappa B; Organ Size; RNA, Messenger; RNA, Viral; Transcription Factor AP-1; Ventricular Dysfunction, Left; Viral Core Proteins

A reduction of coronary flow reserve has been reported in patients with hypertensive heart disease (HHD), which suggests that myocardial ischemia may contribute to the progression to cardiac failure in HHD. Therefore, we evaluated whether fibroblast growth factor (FGF)-2 and/or heparin, which induce angiogenesis, may affect cardiac function in the setting of HHD. We used Dahl salt sensitive (DS) rats as an HHD model. Direct intramyocardial injection of 100 microg of FGF-2 plus 1.28 microg of heparin (n = 6), 100 microg of FGF-2 (n = 6), 1.28 microg of heparin (n = 6) or saline (n = 6) were performed in 9-week-old rats. Echocardiography was performed to evaluate cardiac function at 9, 11, and 13 weeks of age. Plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) concentrations were measured at 8 and 13 weeks of age. DS rats were killed 4 weeks after myocardial injection (at 13 weeks of age), and myocardial capillary density was assessed by von Willebrand factor staining. Injection of FGF-2 plus heparin significantly decreased left ventricular end-diastolic diameter (P < 0.0001) and left ventricular end-systolic diameter (P < 0.0001), significantly improved the reduction of left ventricular fractional shortening (P = 0.0005), significantly decreased plasma ANP (P < 0.0001) and BNP (P = 0.016) concentrations, and significantly increased myocardial capillary density (P = 0.0002) compared with injection of saline. These findings indicate that intramyocardial injection of FGF-2 plus heparin suppresses the progression of cardiac failure in DS rats. FGF-2 plus heparin administration may be a new therapeutic strategy for the treatment of HHD.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Echocardiography; Fibroblast Growth Factor 2; Heart Failure; Heart Rate; Heparin; Hypertension; Hypertrophy, Left Ventricular; Injections; Male; Myocardium; Natriuretic Peptide, Brain; Neovascularization, Pathologic; Rats; Rats, Inbred Dahl; Ventricular Function

In this study we examined diabetes- and hypertension-induced changes in cardiac structure and function in an animal model of type 2 diabetes, the Goto-Kakizaki (GK) rat. We hypothesized that treatment with omapatrilat, a vasopeptidase inhibitor, which causes simultaneous inhibition of angiotensin converting enzyme and neutral endopeptidase, provides additional cardioprotective effects, during normal- as well as high sodium intake, compared to treatment with enalapril, a selective inhibitor of angiotensin converting enzyme. Fifty-two GK rats were randomized into 6 groups to receive either normal-sodium (NaCl 0.8%) or high-sodium (NaCl 6%) diet and enalapril, omapatrilat or vehicle for 12 weeks. The GK rats developed hypertension, cardiac hypertrophy and overexpression of cardiac natriuretic peptides and profibrotic connective tissue growth factor compared to nondiabetic Wistar rats. The high dietary sodium further increased the systolic blood pressure, and changed the mitral inflow pattern measured by echocardiography towards diastolic dysfunction. Enalapril and omapatrilat equally decreased the systolic blood pressure compared to the control group during normal- as well as high-sodium diet. Both drugs had beneficial cardioprotective effects, which were blunted by the high dietary sodium. Compared to enalapril, omapatrilat reduced the echocardiographically measured left ventricular mass during normal-sodium diet and improved the diastolic function during high-sodium diet in GK rats. Furthermore, omapatrilat reduced relative cardiac weight more effectively than enalapril during high sodium intake. Our results suggest that both the renin-angiotensin and the neutral endopeptidase system are involved in the pathogenesis of diabetic cardiomyopathy since vasopeptidase inhibition was shown to provide additional benefits in comparison with selective angiotensin converting enzyme inhibition alone.

Topics: Aldosterone; Angiotensin-Converting Enzyme Inhibitors; Animals; Atrial Natriuretic Factor; Blood Glucose; Blood Pressure; Body Weight; Cardiomegaly; Collagen; Diabetes Mellitus, Type 2; Echocardiography; Enalapril; Fibrosis; Heart; Insulin; Male; Metalloendopeptidases; Myocardium; Natriuretic Peptide, Brain; Organ Size; Protease Inhibitors; Pyridines; Random Allocation; Rats; Rats, Wistar; RNA, Messenger; Sodium Chloride, Dietary; Thiazepines

The association between higher body mass index (BMI) and lower B-type natriuretic peptide (BNP) level is thought to be mediated by expression of the natriuretic peptide clearance receptor (NPR-C) in adipose tissue. To explore this association, we tested 2 hypotheses: (1) that N-terminal (NT)-proBNP, which is not believed to bind NPR-C, would not be associated with BMI and (2) that lower BNP would be more closely associated with fat mass than with lean mass.. Measurements of BNP, NT-proBNP, and body composition by direct dual energy x-ray absorptiometry (DEXA) were performed in 2707 subjects from the Dallas Heart Study. The associations between obesity and low BNP (<4 ng/L) or low NT-proBNP (lowest sex-specific quartile) were evaluated with multivariable logistic regression models stratified by sex and adjusted for age, race/ethnicity, hypertension, left ventricular mass, and end-diastolic volume. Higher BMI was independently associated with lower BNP and NT-proBNP (all P<0.001). When BMI was replaced with both DEXA-derived lean and fat mass, greater lean mass, but not fat mass, was associated with low BNP and NT-proBNP levels.. In a large, population-based cohort, we confirm the previously described association between higher BMI and lower BNP and demonstrate a similar inverse association between BMI and NT-proBNP. Interestingly, both BNP and NT-proBNP are more closely associated with lean mass than with fat mass. These findings do not support the hypothesis that the lower BNP levels seen in obesity are driven by enhanced BNP clearance mediated via NPR-C.

Topics: Absorptiometry, Photon; Adult; Aged; Biomarkers; Body Composition; Body Weight; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Texas

Pulmonary arterial hypertension complicated by decompensated cor pulmonale is a challenging clinical problem with few effective therapeutic options. B-type natriuretic peptide is a pluripotent hormone that promotes diuresis and natriuresis, vasodilates systemic and pulmonary vessels, and reduces circulating levels of endothelin and aldosterone. It may represent a possible therapeutic strategy for decompensated cor pulmonale in the same manner that it is used to treat decompensated left heart failure. The authors report their experience with B-type natriuretic peptide as adjunctive therapy for pulmonary arterial hypertension complicated by decompensated cor pulmonale. A detailed case report is presented followed by the evaluation of a series of 11 cases occurring in eight patients from December 2002 through April 2004.

Topics: Adult; Aged; Blood Pressure; Body Weight; Cardiac Output; Clinical Nursing Research; Disease Progression; Drug Monitoring; Dyspnea; Echocardiography, Transesophageal; Female; Heart Failure; Humans; Hypertension, Pulmonary; Infusions, Intravenous; Male; Middle Aged; Natriuretic Agents; Natriuretic Peptide, Brain; Pulmonary Heart Disease; Pulmonary Wedge Pressure; Severity of Illness Index; Treatment Outcome

Angiotensin converting enzyme (ACE) inhibitors inhibit both the formation of angiotensin II and the catabolism of bradykinin (BK). They prevent not only hypertension but also cardiac hypertrophy and fibrosis. An increase in BK level stimulates the expression of nitric oxide (NO) synthase (NOS) and induces prostaglandins, both of which are powerful vasodilator factors. The direct effect of BK against cardiac hypertrophy is still unclear. This study was performed to examine the cardioprotective effects of BK in hypertrophic models. Renovascular hypertensive (RHT) rats were treated with BK (1,000 ng/kg/day), BK+D-arginyl-[Hyp(3), Thi(5), D-Tic(7), Oic(8)]-bradykinin (HOE140) (a BK B(2) receptor antagonist), and BK+N(omega)-nitro-L-arginine methyl ester (L-NAME) (a NOS inhibitor) for 3 weeks. Blood pressure was measured and echocardiographic analysis performed during the treatment. Histological data were analyzed to confirm the hypotrophic effect of BK. Treatment with BK improved cardiac remodeling, reducing both the heart weight/body weight ratio and the left ventricular wall thickness. However, co-treatment with HOE140 or L-NAME reversed the anti-hypertrophic action of BK. In particular, cardiac fibrosis or perivascular fibrosis, along with collagen accumulation, were inhibited by treatment with BK, while HOE140 and L-NAME counteracted these changes. In addition, expressions of atrial natriuretic peptides (ANP) and brain natriuretic peptides (BNP), which are markers of cardiac abnormalities, were down-regulated by treatment with BK. These effects were reversed by co-treatment with HOE140 and L-NAME. Together, these results indicate that BK directly inhibits the progression of cardiac hypertrophy and cardiac fibrosis due to NO release via the BK B(2) receptor. The BK-NO pathway may play an important role in the progression of cardiac remodeling.

Topics: Adrenergic beta-Antagonists; Animals; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Bradykinin; Coronary Circulation; Echocardiography; Enzyme Inhibitors; Fibrosis; Hypertension, Renal; Hypertrophy, Left Ventricular; Male; Myocardium; Natriuretic Peptide, Brain; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Organ Size; Rats; Rats, Wistar; RNA, Messenger; Ventricular Remodeling

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

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Blood Specimen Collection; Body Weight; Female; Fourier Analysis; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Periodicity; Ventricular Dysfunction, Left

The formation of advanced glycation end products (AGEs) on extracellular matrix components leads to accelerated increases in collagen cross linking that contributes to myocardial stiffness in diabetes. This study determined the effect of the crosslink breaker, ALT-711 on diabetes-induced cardiac disease. Streptozotocin diabetes was induced in Sprague-Dawley rats for 32 weeks. Treatment with ALT-711 (10 mg/kg) was initiated at week 16. Diabetic hearts were characterized by increased left ventricular (LV) mass and brain natriuretic peptide (BNP) expression, decreased LV collagen solubility, and increased collagen III gene and protein expression. Diabetic hearts had significant increases in AGEs and increased expression of the AGE receptors, RAGE and AGE-R3, in association with increases in gene and protein expression of connective tissue growth factor (CTGF). ALT-711 treatment restored LV collagen solubility and cardiac BNP in association with reduced cardiac AGE levels and abrogated the increase in RAGE, AGE-R3, CTGF, and collagen III expression. The present study suggests that AGEs play a central role in many of the alterations observed in the diabetic heart and that cleavage of preformed AGE crosslinks with ALT-711 leads to attenuation of diabetes-associated cardiac abnormalities in rats. This provides a potential new therapeutic approach for cardiovascular disease in human diabetes.

Topics: Animals; Blood Pressure; Body Weight; Collagen; Cytokines; Diabetes Mellitus, Experimental; Gene Expression Regulation; Glycation End Products, Advanced; Heart Ventricles; Hypertrophy, Left Ventricular; Immunohistochemistry; Male; Myocardium; Natriuretic Peptide, Brain; Organ Size; Rats; Rats, Sprague-Dawley; Receptor for Advanced Glycation End Products; Receptors, Immunologic; Thiazoles

Pericardial effusion has recently been reported as a complication of anorexia nervosa. A distinct pathophysiological cause of it could not be revealed. In some reports, there was a probable correlation between weight gain and reduction of pericardial effusion in anorexia nervosa cases. We encountered a case in which pericardial effusion remitted completely along with body weight increase and normalization of low T3 syndrome. These findings suggest that the reduction of pericardial effusion may correlate with both weight gain and low T3 normalization. Plasma brain natriuretic peptide (BNP) levels were increased in this case despite heart failure, and plasma BNP decreased as pericardial effusion remitted. The measurement of serum BNP level may be a clinical parameter in such a case of pericardial effusion.

Topics: Adult; Anorexia Nervosa; Biomarkers; Body Weight; Echocardiography; Female; Humans; Natriuretic Peptide, Brain; Pericardial Effusion; Remission, Spontaneous; Treatment Outcome; Weight Gain

Growing evidence suggests that the autoimmune mechanism plays an important role in the pathogenesis of dilated cardiomyopathy. The purpose of this study was to evaluate the effect on the cardiac structure and function by the transfer of immunoglobulin G (IgG) and/or lymphocytes from rabbits immunized with a synthetic peptide corresponding to the sequence of the second extracellular loop of beta1-adrenoceptor (beta peptide) into severe combined immunodeficiency (SCID) mice. CB-17 SCID mice were injected intraperitoneally with 2 mg of IgG and/or 1 x 10(7) peripheral blood lymphocytes (PBL) from either rabbits immunized with both beta1 peptide and adjuvant (beta group), and adjuvant or rabbits with adjuvant only (N group). Thirty-five SCID mice were divided into seven groups: (1) N-IgG group; (2) N-PBL group; (3) N-IgG+PBL group; (4) beta-IgG group; (5) beta-PBL group; (6) beta-IgG+PBL group; and (7) control group. Morphological, serological and endocrinological studies were performed 70 days after the transfer. Results showed that heart weight and heart weight/body weight ratio in the beta-IgG+PBL group tended to be increased as compared with those in other groups. All mice in the beta-IgG group, two in the beta-PBL group and four in the beta-IgG+PBL group showed high titer of rabbit anti-beta1-adrenoceptor antibodies. Brain natriuretic peptide in the beta-IgG+PBL group showed a significant increase as compared with those in the control group and N-IgG+PBL. Pathohistologically, focal infiltration of inflammatory cells in the myocardium was observed in one mouse of the beta-IgG+PBL group. Rabbit CD3-positive T-lymphocytes in the myocardium were observed in two mice of the beta group. In conclusion, transfer of IgG and PBL from rabbits immunized with beta1 peptide was able to induce the early stages of myocardial damage in SCID mice. These data provide direct evidence that the autoimmune mechanism is important in the pathogenesis of dilated cardiomyopathy.

Topics: Adoptive Transfer; Animals; Autoantibodies; Autoimmune Diseases; Body Weight; Cardiomyopathies; Disease Models, Animal; Female; Heart; Immunoglobulin G; Injections, Intraperitoneal; Lymphocyte Transfusion; Male; Mice; Mice, SCID; Myocardium; Natriuretic Peptide, Brain; Organ Size; Rabbits; Receptors, Adrenergic, beta-1; Severe Combined Immunodeficiency; T-Lymphocytes

Acute intravenous administration of moxonidine, an imidazoline I1-receptor agonist, reduces blood pressure (BP) in normotensive and hypertensive rats, induces diuresis and natriuresis, and stimulates plasma atrial natriuretic peptide (ANP). In these studies we investigated the involvement of natriuretic peptides (ANP and brain natriuretic peptide) in the effects of chronic activation of imidazoline receptors.. Spontaneously hypertensive rats (SHR; 12 to 14 weeks old) received 7-day moxonidine treatment at various doses (10, 20, 60, and 120 microg/kg/h) via subcutaneously implanted osmotic minipumps.. Hemodynamic parameters (continuously monitored by telemetry) revealed that, compared with saline-treated rats, moxonidine dose-dependently decreased blood pressures (BPs). Maximal blood pressure lowering effect was achieved by day 4 of treatment, at which point 60 microg/kg/h reduced mean arterial pressure (MAP) by 14.5 +/- 6.8 mm Hg as compared with basal levels. The decrease in MAP was influenced by a drop in both diastolic and systolic pressures. Moxonidine treatment did not alter daily urinary sodium and potassium excretions, but 120 microg/kg/h moxonidine decreased urine volume after 2 days and increased cyclic guanosine 3'5'monophosphate excretion on days 4 to 7 of treatment. Chronic moxonidine treatment dose-dependently increased plasma ANP to reach, at 120 microg/kg/h, a 40% increase (P < .01) above that of corresponding saline-treated SHR, with a concomitant increase in left and right atrial ANP mRNA (more than twofold). Plasma BNP increased by 120 microg/kg/h moxonidine (11.0 +/- 1.1 v 16.5 +/- 1.9 pg/mL, P < .002) without significant increases in atrial and ventricular BNP mRNA.. ANP and BNP may be involved in the antihypertensive effect of chronic moxonidine treatment. Accordingly, natriuretic peptides may contribute to the sympatholytic and cardioprotective effects of chronic activation of imidazoline I1-receptors.

Topics: Animals; Antihypertensive Agents; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Female; Gene Expression; Imidazoles; Imidazoline Receptors; Natriuretic Peptide, Brain; Rats; Rats, Inbred SHR; Receptors, Drug

Guanylyl cyclase (GC)-A, a natriuretic peptide receptor, lowers blood pressure and inhibits the growth of cardiac myocytes and fibroblasts. Angiotensin II (Ang II) type 1A (AT1A), an Ang II receptor, regulates cardiovascular homeostasis oppositely. Disruption of GC-A induces cardiac hypertrophy and fibrosis, suggesting that GC-A protects the heart from abnormal remodeling. We investigated whether GC-A interacts with AT1A signaling in the heart by target deletion and pharmacological blockade or stimulation of AT1A in mice.. We generated double-knockout (KO) mice for GC-A and AT1A by crossing GC-A-KO mice and AT1A-KO mice and blocked AT1 with a selective antagonist, CS-866. The cardiac hypertrophy and fibrosis of GC-A-KO mice were greatly improved by deletion or pharmacological blockade of AT1A. Overexpression of mRNAs encoding atrial natriuretic peptide, brain natriuretic peptide, collagens I and III, transforming growth factors beta1 and beta3, were also strongly inhibited. Furthermore, stimulation of AT1A by exogenous Ang II at a subpressor dose significantly exacerbated cardiac hypertrophy and dramatically augmented interstitial fibrosis in GC-A-KO mice but not in wild-type animals.. These results suggest that cardiac hypertrophy and fibrosis of GC-A-deficient mice are partially ascribed to an augmented cardiac AT1A signaling and that GC-A inhibits AT1A signaling-mediated excessive remodeling.

Topics: Angiotensin II; Angiotensin Receptor Antagonists; Angiotensinogen; Animals; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Cardiomegaly; Collagen; Fibrosis; Gene Targeting; Guanylate Cyclase; Heart Rate; Heart Ventricles; Hypertension; Imidazoles; Mice; Mice, Knockout; Myocardium; Natriuretic Peptide, Brain; Olmesartan Medoxomil; Organ Size; Peptidyl-Dipeptidase A; Receptor, Angiotensin, Type 1; Receptors, Angiotensin; Receptors, Atrial Natriuretic Factor; RNA, Messenger; Tetrazoles; Transforming Growth Factor beta; Transforming Growth Factor beta1; Transforming Growth Factor beta2; Ventricular Remodeling

B-type natriuretic peptide (BNP) plasma concentrations are raised in patients with heart failure. In several experimental models of cardiac overload, however, BNP mRNA and plasma BNP peptide levels are normal, despite the persistent increase in blood pressure and ventricular hypertrophy. In this study, the role of transcriptional mechanisms in the regulation of BNP gene expression were studied in angiotensin (Ang) II-induced hypertension by injecting DNA constructs containing the BNP promoter (-2200 to 75 bp of the transcriptional start site) linked to luciferase reporter into rat myocardium. Ang II was administered to conscious rats via intravenous infusion for 2 hours or by subcutaneous minipumps for 6 hours, 12 hours, 3 days, 1 week, and 2 weeks. Ang II increased blood pressure and cardiac mass and induced changes in diastolic function. The left ventricular BNP mRNA levels increased 2.2-fold (P<0.001) at 2 hours and peaked at 12 hours (5.2-fold, P<0.001). Thereafter, BNP mRNA levels decreased (1.8-fold induction at 3 days, P<0.05) and returned to control levels at 1 week, despite persistent hypertension and myocardial hypertrophy. Left ventricular BNP peptide concentrations followed the changes in BNP mRNA levels. The BNP promoter was activated 2.7-fold (P<0.05) at 2 hours and remained upregulated up to 2 weeks (2.8-fold, P<0.05) during Ang II infusion, except at 12 hours. These results indicate that posttranscriptional control plays a major role in the regulation of ventricular BNP gene expression in Ang II-induced hypertension.

Topics: Angiotensin II; Animals; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Echocardiography; Gene Expression Regulation; Heart Rate; Heart Ventricles; Hypertension; Male; Natriuretic Peptide, Brain; Organ Size; Promoter Regions, Genetic; Protein Binding; Rats; Rats, Sprague-Dawley; RNA Processing, Post-Transcriptional; RNA, Messenger; Transcription Factor AP-1

Aldosterone breakthrough during ACE inhibitor therapy has been reported. This study investigates changes in plasma aldosterone concentration (PAC) and its mechanism and effects on target organ damage during long-term angiotensin II type 1 (AT1) receptor antagonist (AT1A) therapy in hypertensive rats. An AT1A (candesartan, 1 mg/kg per day PO) was administered in stroke-prone spontaneously hypertensive rats from 4 weeks of age for 34 weeks. PAC was significantly decreased during the first 4 weeks but showed aldosterone breakthrough after 8 weeks of AT1A administration. Plasma angiotensin II concentration was significantly elevated, whereas no change was seen in plasma ACTH or serum potassium. The mechanism(s) of aldosterone breakthrough were investigated by giving high doses of candesartan (3 mg/kg per day PO), dexamethasone (200 microg/kg per day IP), or the AT2 antagonist (PD123319, 10 mg/kg per day SC) during the last week of the 24-week AT1A treatment period. Dexamethasone and AT2 antagonist but not high-dose AT1A produced a significant decrease in PAC, with a larger decrease produced by the AT2 antagonist. To clarify the effects of the residual aldosterone, effects of coadministration of low-dose spironolactone (10 mg/kg per day SC), an aldosterone antagonist, on left ventricular hypertrophy and expression of brain natriuretic peptide mRNA were determined. Low-dose spironolactone further improved left ventricular hypertrophy and brain natriuretic peptide mRNA expression despite no additional depressor effect. These results suggest that aldosterone breakthrough occurs during long-term AT1A therapy, mainly by an AT2-dependent mechanism. Residual aldosterone may attenuate the cardioprotective effects of AT1A.

Topics: Adrenocorticotropic Hormone; Aldosterone; Angiotensin II; Angiotensin Receptor Antagonists; Animals; Anti-Inflammatory Agents; Antihypertensive Agents; Benzimidazoles; Biphenyl Compounds; Blood Pressure; Body Weight; Corticosterone; Dexamethasone; Dose-Response Relationship, Drug; Gene Expression Regulation; Hypertension; Imidazoles; Male; Natriuretic Peptide, Brain; Prodrugs; Pyridines; Rats; Rats, Inbred SHR; Rats, Inbred WKY; RNA, Messenger; Spironolactone; Stroke; Tetrazoles; Time Factors

Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) regulate cardiac hypertrophy. We investigated ventricular alterations of ANP and BNP in interleukin-6 (IL-6) transgenic mice (TG) and wild type (WT) mice with or without viral infection. The ANP and BNP mRNA/GAPDH mRNA ratios in the ventricles of IL-6 TG mice were twice that of WT mice, but were not increased significantly by viral inoculation. In WT mice, both ANP and BNP responses were significantly increased in the ventricles of mice 10 days after encephalomyocarditis (EMC) viral inoculation. Cardiac weight in IL-6 TG mice was significantly greater than in WT 10 days after viral inoculation. Left ventricular wall thickness and the diameter of ventricular myocytes also were greater in IL-6 TG than WT after viral infection. Primary cultures of neonatal rat cardiac myocyte showed that IL-6 increased ANP and BNP mRNA expression in a dose-responsive fashion. In summary, overexpression of ANP and BNP occurs in the ventricles of IL-6 TG mice, along with increased cardiac weight after infection with EMC virus, and impaired responses in the expression of ANP and BNP.

Topics: Animals; Atrial Natriuretic Factor; Body Weight; Cardiomegaly; DNA Probes; Encephalomyocarditis virus; Interleukin-6; Mice; Mice, Inbred C57BL; Mice, Transgenic; Natriuretic Peptide, Brain; Organ Size; Rats

In spite of the solid evidence that beta-blockade reduces mortality and morbidity in congestive heart failure (CHF) this therapy continues to be underused in clinical praxis. The reason for this may lie in scarcity of knowledge about the mechanisms of beta-blockade action. The major aim of this study was to investigate in vivo whether selective beta(1)-blockade may improve cardiac energy metabolism in rats with myocardial infarction in early postinfarct remodeling phase. Myocardial infarction (MI) was induced in male Sprague-Dawley rats by ligation of the left coronary artery. Two different groups of rats were studied, rats with MI treated with metoprolol (5 mg/kg/h; n = 9) and rats with MI saline treated (n = 9). The treatment with metoprolol was given by subcutaneously implanted minipumps and was initiated at 3 days postinfarct and during the period of 4 weeks. All rats were investigated with noninvasive methods (31)P magnetic resonance spectroscopy (MRS) and transthoracic echocardiography 3 days after induction of MI and 4 weeks later. Phosphocreatine/ATP ratio was normalized after the treatment with metoprolol while it was 50% lower in the saline group (p < 0.001). In the metoprolol group stroke volume and ejection fraction increased while deceleration time of mitral early filling was longer (all p < 0.05). Left ventricular weight as well as volumes and dimensions were similar between the groups. Plasma levels of noradrenaline (p = 0.058), adrenaline (p < 0.01) and brain natriuretic peptide (p = 0.09) were lower in the metoprolol group. Selective beta(1)-blockade with high dose of metoprolol initiated in the early postinfarct phase improves myocardial energy metabolism and function and prevents overactivation of sympathetic system. The beneficial effect on myocardial bioenergetics may be an important mode of action of beta-blockers which contributes to the clinical benefits of the therapy in CHF.

Topics: Adrenergic beta-Antagonists; Animals; Body Weight; Catecholamines; Echocardiography; Energy Metabolism; Heart; Heart Ventricles; Hemodynamics; Magnetic Resonance Spectroscopy; Metoprolol; Myocardial Infarction; Myocardium; Natriuretic Peptide, Brain; Neurosecretory Systems; Organ Size; Rats; Rats, Sprague-Dawley

Activation of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) is considered a hallmark of myocardial remodeling. To determine magnitude and relative proportion of activation during the progression to heart failure, we assessed ANP and BNP gene expression in atrial and left ventricular (LV) tissue in a newly developed model of progressive rapid ventricular pacing-induced heart failure in rabbits.. Six animals underwent progressive pacing with incremental rates (330 beats per min (bpm) to 380 bpm over 30 days), resulting in congestive heart failure (CHF). Five animals underwent pacing at 330 bpm for 10 days only (early LV dysfunction, ELVD) and five additional animals served as control group (CTRL).. ELVD was characterized by decreased mean arterial pressure (P=0.05 vs. CTRL) as well as significantly impaired LV function (LV fractional shortening (FS) P<0.01 vs. CTRL) and dilatation (P<0.01 vs. CTRL). CHF was characterized by further decreased mean arterial pressure (P<0.01 vs. ELVD), further impaired LV function (FS P<0.03 vs. ELVD) and dilatation (P<0.01 vs. CTRL). In control animals, significant ANP expression was observed only in atrial tissue (P<0.02 vs. BNP) while BNP expression was ubiquitous but marginal (LV P<0.05 vs. ANP). In ELVD, activation of ANP (atria and LV P<0.05 vs. CTRL) and BNP (atria P<0.05 vs. CTRL, LV n.s.) was observed. In CHF, LV-BNP increased further markedly (P<0.01 vs. CTRL, P<0.05 vs. ELVD) while atrial ANP and BNP expression as well as LV ANP expression remained unchanged (all P=n.s. vs. ELVD).. The current studies demonstrate differential activation of atrial and LV ANP and BNP under normal conditions and during the progression to heart failure and provide a molecular basis for the superiority of BNP as marker of LV dysfunction and CHF.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Disease Models, Animal; Disease Progression; Gene Expression; Heart Failure; Male; Myocardium; Natriuretic Peptide, Brain; Organ Size; Rabbits; RNA, Messenger; Ventricular Dysfunction, Left

To evaluate the effect of age and body weight on several neurohumoral variables that are commonly altered in heart failure in Cavalier King Charles Spaniels.. 17 healthy privately owned Cavalier King Charles Spaniels, 10 males and 7 females, ranging in age from 0.4 to 9.7 years, and ranging in body weight from 6.6 to 12.2 kg.. The clinical condition of the dogs was evaluated by physical examination, thoracic radiography, and echocardiography. Plasma nitrate and nitrite (P-NN), N-terminal atrial natriuretic and brain natriuretic peptides (NT-ANP and BNP, respectively), endothelin (ET-1), urine cyclic guanosine monophosphate (U-cGMP), and urine nitrate and nitrite (U-NN) concentrations were analyzed.. Plasma concentrations of NT-ANP and P-NN increased significantly with age, but plasma NT-ANP and P-NN also correlated significantly, irrespective of age. A modest increase of left atrial size did not explain the increase of NT-ANP and P-NN with age. Concentration of ET-1 correlated positively with heart rate; heart rate did not change with age. Weight had a negative impact on NT-ANP, P-NN, and U-cGMP concentrations and left atrial relative size.. Age-matched controls are essential for evaluation of NT-ANP and P-NN concentrations and left atrial size. Weight may alter reference values of plasma NT-ANP, P-NN, and urine cGMP concentrations. Natriuretic peptides can be used as further evidence that heart failure exists. The increased plasma concentrations of NT-ANP (but not BNP) and P-NN with aging reflect neurohumoral physiologic changes that must be distinguished from pathologic changes in patients with heart failure.

Topics: Age Factors; Animals; Atrial Natriuretic Factor; Body Weight; Cardiac Output; Creatinine; Cyclic GMP; Dogs; Echocardiography; Electrocardiography; Endothelin-1; Female; Heart Failure; Heart Rate; Male; Natriuretic Peptide, Brain; Neurotransmitter Agents; Nitrites; Radiography, Thoracic; Regression Analysis

Pressure overload, such as hypertension, to the heart causes pathological cardiac hypertrophy, whereas chronic exercise causes physiological cardiac hypertrophy, which is defined as athletic heart. There are differences in cardiac properties between these two types of hypertrophy. We investigated whether mRNA expression of various cardiovascular regulating factors differs in rat hearts that are physiologically and pathologically hypertrophied, because we hypothesized that these two types of cardiac hypertrophy induce different molecular phenotypes. We used the spontaneously hypertensive rat (SHR group; 19 wk old) as a model of pathological hypertrophy and swim-trained rats (trained group; 19 wk old, swim training for 15 wk) as a model of physiological hypertrophy. We also used sedentary Wistar-Kyoto rats as the control group (19 wk old). Left ventricular mass index for body weight was significantly higher in SHR and trained groups than in the control group. Expression of brain natriuretic peptide, angiotensin-converting enzyme, and endothelin-1 mRNA in the heart was significantly higher in the SHR group than in control and trained groups. Expression of adrenomedullin mRNA in the heart was significantly lower in the trained group than in control and SHR groups. Expression of beta(1)-adrenergic receptor mRNA in the heart was significantly higher in SHR and trained groups than in the control group. Expression of beta(1)-adrenergic receptor kinase mRNA, which inhibits beta(1)-adrenergic receptor activity, in the heart was markedly higher in the SHR group than in control and trained groups. We demonstrated for the first time that the manner of mRNA expression of various cardiovascular regulating factors in the heart differs between physiological and pathological cardiac hypertrophy.

Topics: Actins; Adrenomedullin; Animals; Blood Pressure; Body Weight; Cardiomegaly; Disease Models, Animal; Gene Expression Regulation; Hemodynamics; Natriuretic Peptide, Brain; Peptides; Peptidyl-Dipeptidase A; Phenotype; Physical Conditioning, Animal; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptor, Muscarinic M2; Receptors, Adrenergic, beta-1; Receptors, Muscarinic; Reference Values; Swimming; Transcription, Genetic

To determine the role of endothelin-1 (ET-1) in the upregulation of atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) observed in deoxycorticosterone acetate (DOCA)-salt hypertension, the selective ET-1 type-A receptor (ET(A)) antagonist ABT-627 was chronically administered to normal controls and hypertensive rats. Chronic ET(A) blockade in DOCA-salt-treated rats prevented the increase in blood pressure and circulating natriuretic protein (NP) levels and partially prevented left ventricular hypertrophy. The changes observed in NP gene expression in the atria were not affected by ABT-627. In the ventricles, ABT-627 reduced NP gene expression. Rats receiving the ET(A) antagonist alone showed reduced left ventricular NP gene expression. ABT-627 did not affect ventricular collagen III gene expression but enhanced left ventricular alpha-myosin heavy chain expression. These findings suggest that in vivo, ventricular but not atrial NP production is regulated by ET-1. This difference in response between atrial and ventricular NP gene expression to ET(A) receptor blockade is similar to that observed by us after applying angiotensin-converting enzyme inhibitors in other hypertensive models. In general therefore, atrial NP gene expression may not be as sensitive to the endocrine environment as is ventricular NP gene expression.

Topics: Animals; Atrasentan; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Desoxycorticosterone; Endothelin Receptor Antagonists; Gene Expression Regulation; Heart; Heart Ventricles; Hypertension; Male; Myocardium; Myosin Heavy Chains; Natriuretic Peptide, Brain; Organ Size; Pyrrolidines; Rats; Rats, Sprague-Dawley; Receptor, Endothelin A; Sodium, Dietary; Transcription, Genetic

The aims of this study were to examine, in vivo, the effects of GH treatment on myocardial energy metabolism, function, morphology, and neurohormonal status in rats during the early postinfarct remodeling phase. Myocardial infarction (MI) was induced in male Sprague Dawley rats. Three different groups were studied: MI rats treated with saline (n = 7), MI rats treated with GH (MI + GH; n = 11; 3 mg/kg x day), and sham-operated rats (sham; n = 8). All rats were investigated with 31P magnetic resonance spectroscopy and echocardiography at 3 days after MI and 3 weeks later. After 3 weeks treatment with GH, the phosphocreatine/ATP ratio increased significantly, compared with the control group (MI = 1.69 +/- 0.09 vs. MI + GH = 2.42 +/- 0.05, P < 0.001; sham = 2.34 +/- 0.08). Treatment with GH significantly attenuated an increase in left ventricular end systolic volume and end diastolic volume. A decrease in ejection fraction was prevented in GH-treated rats (P < 0.05 vs. MI). Myocardial and plasma noradrenaline levels were significantly lower in MI rats treated with GH. These effects were accompanied by normalization of plasma brain natriuretic peptide levels (sham = 124.1 +/- 8.4; MI = 203.9 +/- 34.7; MI + GH = 118.3 +/- 8.4 ng/ml; P < 0.05 vs. MI). In conclusion, GH improves myocardial energy reserve, preserves left ventricular function, and attenuates pathologic postinfarct remodeling in the absence of induction of left ventricular hypertrophy in postinfarct rats. The marked decrease in myocardial content of noradrenaline, after GH treatment, may protect myocardium from adverse effects of catecholamines during postinfarct remodeling.

Topics: Animals; Body Weight; Catecholamines; Dopamine; Echocardiography, Doppler; Energy Metabolism; Epinephrine; Hemodynamics; Human Growth Hormone; Insulin-Like Growth Factor I; Male; Myocardial Infarction; Myocardium; Natriuretic Peptide, Brain; Rats; Rats, Sprague-Dawley; Receptors, Adrenergic, beta; Ventricular Function, Left

Although heme oxygenase (HO) has been suggested to be involved in the regulation of cardiovascular function through production of carbon monoxide (CO), the pathophysiological significance of HO in hypertensive organ damage remains unknown. We examined the effects of inducing HO-1 mRNA by stannous chloride (SnCl2) on cardiac hypertrophy in stroke-prone spontaneously hypertensive rats (SHR-SP/Izm). Chronic administration of SnCl2 resulted in a significant decrease in left ventricular (LV) weight/body weight ratio and LV brain natriuretic peptide (BNP) mRNA levels as a marker of cardiac hypertrophy and a significant increase in LV HO-1 mRNA levels and LV cGMP contents in SHR-SP/Izm, while there was no significant change in systemic blood pressure. These results provide the first evidence that induction of HO in the heart attenuates cardiac hypertrophy in load-independent mechanism in genetically hypertensive rats.

Topics: Animals; Blood Pressure; Body Weight; Cyclic GMP; Enzyme Induction; Heart Rate; Heart Ventricles; Heme Oxygenase (Decyclizing); Heme Oxygenase-1; Hypertension; Hypertrophy, Left Ventricular; Male; Natriuretic Peptide, Brain; Organ Size; Rats; Rats, Inbred SHR; Rats, Inbred WKY; RNA, Messenger; Tin Compounds

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) upregulation are genetic markers for the chronic hypertrophic phenotype but also have important acute physiologic effects on salt and water balance and blood pressure control. The presence of a dual NP-system led us to hypothesize a differential expression of ANP and BNP in response to an acute hemodynamic stress of volume overload in the left ventricle (LV) and right ventricle (RV). Accordingly, we examined the temporal relationship between the RV and LV expression of ANP and BNP mRNA and NP receptor mRNA levels on days 1, 2, 3, and 7 after induction of aortocaval fistula in the rat. LV end-diastolic pressure was increased 1.5-fold by day 3 and 2.0-fold by day 7 compared to control (P<0.05). LV weight increased by day 7 compared to control (2.34+/-0.04 vs 3.07+/-0.10 mg/g, P<0.05) while RV weight did not change over the 7 days. There was a 7-fold increase of ANP mRNA in LV at day 1, which was sustained through day 7, while LV BNP mRNA levels did not differ from controls over the 7 days. In contrast, RV mRNA transcript levels for ANP and BNP were increased >2-fold by day 2 and this increase was sustained throughout 7 days. NP clearance receptor was decreased by 75% by day 7 in the LV but did not change in the RV. Thus, LV ANP mRNA levels increased before the onset of LV hypertrophy and RV BNP mRNA levels increased in the absence of RV hypertrophy. The disparate response of BNP and the NP clearance receptor transcript levels in the LV and RV may be related to differences in load and/or differential expression of the NP system in the LV and RV in response to acute haemodynamic stress.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Cardiomegaly; Gene Expression Regulation; Hemodynamics; Male; Myocardium; Natriuretic Peptide, Brain; Organ Size; Rats; Rats, Sprague-Dawley; Receptors, Atrial Natriuretic Factor; RNA, Messenger; Transcription, Genetic

Brain natriuretic peptide (BNP) is a pulmonary vasodilator that is elevated in the right heart and plasma of hypoxia-adapted rats. To test the hypothesis that BNP protects against hypoxic pulmonary hypertension, we measured right ventricular systolic pressure (RVSP), right ventricle (RV) weight-to-body weight (BW) ratio (RV/BW), and percent muscularization of peripheral pulmonary vessels (%MPPV) in rats given an intravenous infusion of BNP, atrial natriuretic peptide (ANP), or saline alone after 2 wk of normoxia or hypobaric hypoxia (0.5 atm). Hypoxia-adapted rats had higher hematocrits, RVSP, RV/BW, and %MPPV than did normoxic controls. Under normoxic conditions, BNP infusion (0.2 and 1.4 micro g/h) increased plasma BNP but had no effect on RVSP, RV/BW, or %MPPV. Under hypoxic conditions, low-rate BNP infusion (0.2 micro g/h) had no effect on plasma BNP or on severity of pulmonary hypertension. However, high-rate BNP infusion (1.4 micro g/h) increased plasma BNP (69 +/- 8 vs. 35 +/- 4 pg/ml, P < 0.05), lowered RV/BW (0.87 +/- 0.05 vs. 1.02 +/- 0.04, P < 0.05), and decreased %MPPV (60 vs. 74%, P < 0.05). There was also a trend toward lower RVSP (55 +/- 3 vs. 64 +/- 2, P = not significant). Infusion of ANP at 1.4 micro g/h increased plasma ANP in hypoxic rats (759 +/- 153 vs. 393 +/- 54 pg/ml, P < 0.05) but had no effect on RVSP, RV/BW, or %MPPV. We conclude that BNP may regulate pulmonary vascular responses to hypoxia and, at the doses used in this study, is more effective than ANP at blunting pulmonary hypertension during the first 2 wk of hypoxia.

Topics: Animals; Antihypertensive Agents; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Heart Ventricles; Hemodynamics; Histocytochemistry; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Hypoxia; Lung; Male; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Rats; Rats, Sprague-Dawley; Vasodilator Agents

The increase in natriuretic peptides (NP), atrial natriuretic factor (ANF), and brain natriuretic peptide (BNP) production and release by cardiocytes that occurs in hypertension has been considered to be a compensatory mechanism against ventricular overload. Studies on NP production in the spontaneously hypertensive rat (SHR), an experimental model of human hypertension, have produced controversial results and were carried out when hypertension was already established (> 17 weeks). At this time, age-related physiologic and molecular changes in cardiac muscle are difficult to separate from those related to hypertension, ie, increased ANF production and plasma levels. In addition, most of the studies used male rats because the rate of increase in arterial blood pressure--as well as the level to which it rises--is greater in males than in females. Studies of a similar nature using female SHR are not available. The aim of this work was to determine 1) whether ANF and BNP production and secretion increase with the development of hypertension in genetically hypertensive rats; 2) whether a sexual dimorphism in ANF and BNP production and secretion is present in the genetically hypertensive rat during the development of hypertension; and 3) whether the demand for ANF and BNP is the same from each chamber of the heart under these experimental conditions. Age-matched male and female SHR, Wistar-Kyoto (WKY), and Sprague Dawley (SD) rats at 2, 4, and 8 weeks of age were used. The normotensive SD were included to provide a wider basis for baseline findings, as WKY rats are not always a suitable control for SHR due to genetic variations. Natriuretic peptide plasma levels and tissue content were measured by radioimmunoassay. ANF, BNP, as well as alpha- and beta-myosin heavy chain (MHC) mRNA were estimated by Northern blot analysis. Blood pressure (BP) of more than 150 mm Hg was found only in 8-week-old male SHR. Plasma immunoreactive (ir)ANF and irBNP increased significantly at puberty (8 weeks) in both male and female SHR. The earliest molecular change encountered during the development of hypertension was a significant increase in BNP mRNA in the right and left atria from both male and female 8-week-old SHR. In the ventricles from both male and female SHR, there was no increase in the ratio of left ventricular wet weight/body weight, no increase in ventricular ANF mRNA transcripts, and no myosin heavy chain isoform switch (a protein marker of hypertrophy). irBNP ventri

Topics: Age Factors; Animals; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Female; Gene Expression; Heart Ventricles; Hypertension; Male; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Rats, Sprague-Dawley; Sex Factors

Accordingly, we induced streptozotocin diabetes in rats and evaluated the effects of ligating the coronary artery to produce myocardial infarct by analyzing hemodynamics and the expression of brain natriuretic peptide (BNP) messenger (m) RNA. Eight-week diabetic rats and age-matched nondiabetic rats underwent ligation of the coronary artery for 1 week. Left ventricular end-diastolic pressure (LVEDP) was not statistically different between diabetic rats (15+/-6 mmHg) and nondiabetic rats (13+/-9 mmHg) 1 week after coronary ligation, size of infarct, systolic blood pressure were also similar in both groups after coronary ligation. The BNP mRNA/beta-actin mRNA ratio in right ventricle of nondiabetic rats with MI was increased to 350+/-60%, however, in diabetic rats with MI, that was slightly increased to 200+/-50% (P < 0.01). The level of BNP mRNA in the left ventricle of diabetic rats with MI was not increased significantly (120+/-30% versus that in diabetic rats without MI), although that in left ventricle of nondiabetic rats with MI was increased to 280+/-40% versus nondiabetic rats without MI (P < 0.01). Cardiac BNP synthesis in diabetic rats completely reverted to control levels after insulin therapy.

Topics: Animals; Body Weight; Coronary Vessels; Diabetes Mellitus, Experimental; Gene Expression; Heart; Hemodynamics; Insulin; Ligation; Male; Myocardial Infarction; Natriuretic Peptide, Brain; Organ Size; Rats; Rats, Wistar; RNA, Messenger

Chronic pressure overload is known to increase cardiac mass and expression levels of both atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) mRNAs. Although mechanical stretching of cardiac myocytes could cause these changes, humoral factor(s) secondary to pressure overload may also be involved. To dissociate humoral effects from the effects of mechanical loading on cardiac hypertrophic responses, we examined expression of ANP and BNP at both mRNA and protein levels and proportions of myosin isoforms in transplanted cervical hearts that were mechanically unloaded under conditions with or without hypertension by aortic coarctation. Seven days after transplantation, cardiac atrophy that usually occurs in transplanted hearts without hypertension by coarctation was prevented in the transplanted hearts with hypertension by coarctation. The levels of expression of ANP and BNP mRNAs were increased in the transplanted hearts with relative to those without hypertension by coarctation. The plasma level of angiotensin II was higher in rats with than without hypertension by coarctation. Plasma endothelin-1 levels were not significantly different between the two groups. In addition, levels of expression of ANP and BNP mRNAs were increased in the transplanted hearts without hypertension relative to those in the in situ hearts. The proportion of the V3 myosin isoform was also increased in the transplanted hearts without hypertension relative to the in situ hearts. These results indicate that humoral factor(s) secondary to the pressure overload produced by aortic coarctation enhanced the cardiac hypertrophic response and elevated the levels of mRNAs encoding these embryonic markers. Moreover, our findings regarding ANP and BNP expression in the transplanted hearts provide additional evidence that the fetal genes are reexpressed during the process of cardiac atrophy as well as in cardiac hypertrophy.

Topics: Angiotensin II; Animals; Aortic Coarctation; Atrial Natriuretic Factor; Atrophy; Blood Pressure; Body Weight; Cardiomegaly; Endothelin-1; Heart Rate; Heart Transplantation; Hypertension; Male; Myosins; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Rats; Rats, Inbred Lew; RNA, Messenger; Transcription, Genetic; Transplantation, Heterotopic; Transplantation, Isogeneic

Adaptation of cardiac muscle to prolonged hypobaric hypoxia (770-740 mbar, 2,250-2,550 m), endurance training, and their combination was studied in rats by investigating the gene expression of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) in atria and ventricles. Rats were assigned into the following groups according to the barometric conditions and physical activity; normobaric sedentary (NS), normobaric training, hypobaric sedentary (HS), and hypobaric training (HT). Experimental periods were 10, 21, and 56 days; the groups at 91 days served as recovery groups from exposure to and training in normobaric and hypobaric conditions for 56 days. The right ventricular hypertrophy in HT rats at 10 days and 56 days was associated with elevated BNP mRNA levels (2.1- and 1.7-fold, P < 0.05, respectively), whereas hypobaric exposure without training was not sufficient to significantly increase ventricular BNP gene expression, although it lead to hypertrophy of the right ventricle. Right and left atrial BNP mRNA levels were also increased (up to 3.9-fold, P < 0.01) in 10-day HS and 10-day HT groups. ANP mRNA levels in right ventricle and left ventricular epicardium were over twofold higher (P < 0.05-0.01) in 10-day HS and 10-day HT groups in comparison to 10-day NS group. Plasma immunoreactive ANP concentration was increased (P < 0.05) in both hypobaric groups up to 21 days. The results show that exposure to hypobaric hypoxia itself and endurance training in hypobaric, hypoxic conditions lead to a marked early increase in ventricular and atrial ANP and BNP mRNA levels. The adaptational response to hypoxia was more pronounced when the oxygen availability was lowered additionally by endurance training carried out in hypobaric hypoxic conditions.

Topics: Acclimatization; Animals; Atmospheric Pressure; Atrial Natriuretic Factor; Body Weight; Heart; Heart Atria; Hypertrophy, Right Ventricular; Hypoxia; Male; Myocardium; Natriuretic Peptide, Brain; Organ Size; Physical Conditioning, Animal; Rats; Rats, Wistar; RNA, Messenger; Time Factors; Transcription, Genetic

In hypertension with cardiac hypertrophy, the specific contributions to increased production of the cardiac natriuretic peptides (NP) atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) by load and the hypertrophic process are not known. In the present work we determine ANF and BNP synthesis and secretion in the aortic-banded rat treated with dosage schedules of the ACE inhibitor ramipril that result in the prevention or regression of both hypertension and hypertrophy (high dosage) or in the prevention or regression of hypertrophy alone with persistent hypertension (low dosage). Myosin heavy chain (MHC) isoform switch was studied as an indicator of ventricular cardiocyte hypertrophy as well as the levels of collagen III mRNA as a measure of changes in extracellular matrix.. Ramipril was administered for 6 weeks just after suprarenal aortic banding, or rats were banded for 6 weeks, after which ramipril was administered during the following 6 weeks. Banding caused an increase in blood pressure, left ventricular weight-to-body weight ratio, plasma and ventricular NP, ventricular NP mRNA, collagen III, and beta-MHC mRNA. Ramipril at 1 mg/kg normalized all these parameters while ramipril at 10 micrograms/kg normalized left ventricular weight-to-body weight ratio but not blood pressure. Plasma and ventricular NP content and mRNA levels were partially normalized by ramipril (10 micrograms/kg). Ramipril (10 micrograms/kg) prevented increased collagen III mRNA levels but did not affect beta-MHC mRNA levels.. (1) NP production and secretion in aortic-banded rats are independently related to increased blood pressure and hypertrophy. (2) A load-dependent component is more important than a load-independent component in regulating left ventricular NP production. (3) ANF production is more sensitive than BNP production to the load-independent component. (4) Low-dose ramipril treatment reverses hypertrophy and the increased collagen III expression but does not reverse the increased beta-MHC isoform expression, suggesting that these are independently regulated processes. (5) Aortic banding and ACE inhibition do not affect atrial NP production and content.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Aorta; Atrial Natriuretic Factor; Base Sequence; Body Weight; Constriction; Hemodynamics; Hypertension; Hypertrophy, Left Ventricular; Male; Molecular Sequence Data; Myocardium; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Organ Size; Ramipril; Rats; Rats, Sprague-Dawley; Renin

There is experimental evidence indicating that chronic moderate ethanol consumption delays the age-dependent increase in blood pressure. Since the brain natriuretic peptide (BNP) is a potent hypotensive hormone, the effect of chronic ethanol treatment on the heart BNP system was investigated, using spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. Chronic moderate ethanol consumption resulted in significantly lower circulating BNP levels for both SHR (206.9 +/- 18.5 vs. 306.9 +/- 28.1 pg/ml, n = 12, P < or = 0.05) and WKY rats (131.3 +/- 20.7 vs. 220.6 +/- 25.0 pg/ml, n = 12, P < or = 0.05). Left and right atrial BNP content and concentration in WKY rats and left atrial BNP content and concentration in SHR rats were augmented by the ethanol treatment, but not atrial BNP mRNA. In ventricular tissue, alcohol had no effect on total BNP content of either SHR or WKY rats, but it induced a significant elevation in ventricular BNP concentration (microgram/mg protein) and BNP mRNA in SHR, but not WKY rats. Thus, chronic ethanol treatment resulted in specific alterations in the activity of the heart BNP system.

Topics: Age Factors; Alcohol Drinking; Animals; Blood Pressure; Body Weight; Ethanol; Heart; Heart Rate; Male; Myocardium; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Polymerase Chain Reaction; Radioimmunoassay; Rats; Rats, Inbred SHR; Rats, Inbred WKY; RNA, Messenger; Transcription, Genetic

We examined the relationship between cardiac hypertrophy, myosin heavy chain (MHC) isoform expression, and production of atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) before and after the development of DOCA-salt hypertension. DOCA-salt rats exhibited significant left ventricular hypertrophy at the prehypertensive stage (1 week of treatment), without MHC isoform switch or change in natriuretic peptide gene expression. In the hypertensive stage (5 weeks of treatment), pronounced left ventricular hypertrophy was observed, and this was characterized by an increase in beta-MHC protein, resulting in a switch from 90% alpha-MHC to 51% alpha-MHC and 49% beta-MHC. ANF and BNP mRNA levels and peptide content were significantly increased at this stage. Unexpectedly, the MHC isoform switch was evident in the non-hypertrophied right ventricle to the same degree as in the left ventricle. Natriuretic peptide production was also increased in the right ventricle at 5 weeks of treatment, but to a lesser degree than in the left ventricle. In contrast, in the hypertrophied left atrium there was no MHC isoform switch, while ANF and BNP mRNA levels were augmented. Plasma ANF was significantly increased in the prehypertensive stage; this was accompanied by a partial depletion of atrial ANF stores. Plasma BNP was increased only in the hypertensive stage, reflecting an increase in ventricular BNP synthesis and secretion. These results suggest that 1) cardiac hypertrophy, MHC isoform expression, and stimulation of natriuretic peptide production are processes that may be dissociated from each other; 2) increases in plasma ANF without a concomitant increase in plasma BNP reflect atrial hemodynamic overload, while increases in both ANF and BNP in plasma are associated with ventricular hypertrophy; and 3) there exist differences in the storage, secretion, and processing patterns of ANF and BNP in the atria.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Blotting, Northern; Body Weight; Cardiomegaly; Centrifugation, Density Gradient; Chromatography, High Pressure Liquid; Desoxycorticosterone; Hypertension; Isomerism; Male; Myocardium; Myosin Subfragments; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Organ Size; Radioimmunoassay; Rats; Rats, Sprague-Dawley; RNA; Sodium Chloride

1. Plasma human brain natriuretic peptide-like immunoreactivity (hBNP-li) was measured in ten patients with chronic renal failure before and after 4 h of haemodialysis. 2. Plasma hBNP-li was elevated in all patients before dialysis (mean +/- SEM 21.0 +/- 3.8 pmol/l) compared with healthy control subjects (1.3 +/- 0.2 pmol/l, n = 11), but showed considerable inter-patient variability. Before dialysis plasma hBNP-li bore no relationship to the serum creatinine level or to the mean blood pressure. 3. Plasma hBNP-li fell significantly (P = 0.04) during 4 h of haemodialysis. The fall in plasma hBNP-li correlated significantly with the degree of postural blood pressure drop (r2 = 0.44, P = 0.05) and with the fall in body weight (r2 = 0.64, P less than 0.01) after haemodialysis. In all patients, plasma hBNP-li at the end of treatment remained above that in healthy subjects. 4. There was no significant correlation between the fall in plasma hBNP-li and the fall in serum creatinine level, and between the fall in plasma hBNP-li and the fall in supine systolic or diastolic blood pressure, during haemodialysis. 5. We have shown that plasma hBNP-li is elevated in patients with chronic renal failure and is decreased during haemodialysis. The fact that the plasma hBNP-li was not reduced to normal by haemodialysis despite restoration to normovolaemia gives tentative support to the view that, in addition to hypervolaemia, another factor may also be responsible for the elevated plasma hBNP-li seen in these patients.

Topics: Adolescent; Adult; Aged; Blood Pressure; Body Weight; Creatinine; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Posture; Renal Dialysis