atrial-natriuretic-factor and Obesity

Investigations into the mixed muscle-secretory phenotype of cardiomyocytes from the atrial appendages of the heart led to the discovery that these cells produce, in a regulated manner, two polypeptide hormones - the natriuretic peptides - referred to as atrial natriuretic factor or atrial natriuretic peptide (ANP) and brain or B-type natriuretic peptide (BNP), thereby demonstrating an endocrine function for the heart. Studies on the gene encoding ANP (NPPA) initiated the field of modern research into gene regulation in the cardiovascular system. Additionally, ANP and BNP were found to be the natural ligands for cell membrane-bound guanylyl cyclase receptors that mediate the effects of natriuretic peptides through the generation of intracellular cGMP, which interacts with specific enzymes and ion channels. Natriuretic peptides have many physiological actions and participate in numerous pathophysiological processes. Important clinical entities associated with natriuretic peptide research include heart failure, obesity and systemic hypertension. Plasma levels of natriuretic peptides have proven to be powerful diagnostic and prognostic biomarkers of heart disease. Development of pharmacological agents that are based on natriuretic peptides is an area of active research, with vast potential benefits for the treatment of cardiovascular disease.

Topics: Animals; Atrial Appendage; Atrial Fibrillation; Atrial Natriuretic Factor; Atrial Remodeling; Biomarkers; Cyclic GMP; Diabetes Mellitus; Fibrosis; Gene Expression Regulation, Developmental; Heart Atria; Heart Failure; Humans; Hypertension; Lipid Metabolism; Metabolic Syndrome; Mice; Myocardium; Myocytes, Cardiac; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Prognosis; Protein Processing, Post-Translational; Pulmonary Arterial Hypertension; Receptors, Guanylate Cyclase-Coupled; Secretory Vesicles; Ventricular Remodeling; Water-Electrolyte Balance

Midregional pro-atrial natriuretic peptide (MR-proANP), first isolated in 1981, is a novel peptide with multiple biological functions, especially within the cardiovascular system. This peptide plays an important role in many processes, including natriuresis, diuresis, and other physiological and pathophysiological pathways in the human body. Several electronic databases (PubMed, EBSCO, Scopus, and ScienceDirect) were analyzed in the present literature review. The aim of this study was to elucidate the wide roles of MR-proANP, which can be analyzed because of the development of a new sandwich immunoassay, and to determine the possible diagnostic and prognostic implications of MR-proANP on cardiovascular disease and other disorders. The studies discussed in this literature review provide valuable data on the role of ANP in the pathogenesis, diagnostic process, prognosis, and potential therapeutic strategies for disease. Although ANP is mainly associated with cardiovascular disease, it may be used as a biomarker in diabetology, neurology, and metabolic disorders.

Topics: Atrial Natriuretic Factor; Biomarkers; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Obesity; Prognosis; Renal Insufficiency, Chronic

Atrial and B-type Natriuretic Peptides (NP) are cardiac hormones with potent cardiovascular and metabolic effects. They signal through the NPRA/cGMP system and are inactivated by a clearance receptor NPRC and neutral endopeptidases (NEP). Recombinant ANP and BNP are currently used as drug treatment for acute decompensated congestive heart failure. Recent literature indicate that a defective NP system is linked to obesity and predict the risk of type 2 diabetes (T2D). Areas covered: This article reviews recent epidemiological, clinical and preclinical evidences that NP system deficiency may be causal of obesity and T2D. The molecular mechanisms of the NP pathway in several metabolic target tissues are presented. The therapeutic potential of NP in obesity and T2D is discussed. Expert opinion: Targeting the NP pathway may offer a novel therapeutic avenue for the management of obesity and T2D. The benefit/risk of drugs increasing circulating NP levels by blocking NPRC and NEP, and/or enhancing NPRA signaling should be assessed in obese and type 2 diabetic individuals.

Topics: Animals; Atrial Natriuretic Factor; Diabetes Mellitus, Type 2; Humans; Molecular Targeted Therapy; Natriuretic Peptide, Brain; Neprilysin; Obesity; Receptors, Atrial Natriuretic Factor

The natriuretic peptide (NP) family includes atrial natriuretic peptide (ANP), B-type natriuretic peptide, C-type natriuretic peptide and their receptors NPR-A, NPR-B and NPR-C. The effects exerted by this hormonal system in the control of cardiovascular, renal and endocrine functions have been extensively investigated. Moreover, the involvement of NP in the pathogenesis of cardiovascular diseases has been demonstrated. Among the NP components, NPR-C has been described, at the time of its discovery, as the clearance receptor of NP devoid of any physiological functions. Emerging roles of NPR-C, however, have been highlighted over the last few years in relation to its effects on the cardiovascular system and other organs. These effects appear to be directly mediated through distinct cAMP-dependent intracellular mechanisms. Moreover, evidence has been accumulated on a potential pathophysiological role of NPR-C in human diseases. Ongoing studies from our group are revealing its involvement in the mediation of antiproliferative effects exerted on vascular cells by a molecular variant of human ANP. Thus, a new appraisal of NPR-C is overcoming the traditional view of a mere clearance receptor. This review focuses on the most important evidence supporting an involvement of NPR-C in mediating some of the actions of NP and its direct implication in cardiovascular diseases. The current state of knowledge highlights the need of further studies to better clarify the specific roles of NPR-C in pathophysiological processes.

Topics: Atrial Natriuretic Factor; Cardiovascular Diseases; Humans; Hypertension; Natriuretic Peptide, C-Type; Obesity; Phenotype

The objective of this study was to investigate the association between natriuretic peptides, obesity and related comorbidities. A systematic review of the English language literature from 1996 to 2008 was performed with Pubmed/MEDLINE and the ISI Web of Knowledge. 'Natriuretic peptides', 'atrial natriuretic factor', 'brain natriuretic peptide', 'obesity', 'body mass index', 'lipolysis' and 'adipose tissue' were used as Mesh terms. We also conducted a handle search among the references of the original articles selected. Finally, seventy-five studies were considered eligible for inclusion in the review. Natriuretic peptides are widely known as body homeostasis regulators. Recently, their action as lipolytic agents has been identified. Obese patients, especially those with hypertension and metabolic risk factors, have reduced plasma levels of natriuretic peptides. Whether this precedes or follows obesity and its complications remains undefined. The lipolytic effect of natriuretic peptides indicates that they may be involved in the pathophysiology of obesity. In general, studies with obese patients support paradoxical reduced levels of natriuretic peptides. However, the selection of subjects and classification of obesity and heart failure varied among the reviewed studies, rendering comparison unreliable.

Topics: Adipose Tissue; Atrial Natriuretic Factor; Heart Failure; Hemodynamics; Humans; Lipid Metabolism; Lipolysis; Natriuretic Agents; Natriuretic Peptide, Brain; Natriuretic Peptides; Obesity

Natriuretic peptides (NPs) are released from the heart in response to pressure and volume overload. B-type natriuretic peptide (BNP) and N-terminal-proBNP have become important diagnostic tools for assessing patients who present acutely with dyspnea. The NP level reflects a compilation of systolic and diastolic function as well as right ventricular and valvular function. Studies suggest that using NPs in the emergency department can reduce the consumption of hospital resources and can lower costs by either eliminating the need for other, more expensive tests or by establishing an alternative diagnosis that does not require hospital stay. Caveats such as body mass index and renal function must be taken into account when analyzing NP levels. Natriuretic peptide levels have important prognostic value in multiple clinical settings, including in patients with stable coronary artery disease and with acute coronary syndromes. In patients with decompensated heart failure due to volume overload, a treatment-induced drop in wedge pressure is often accompanied by a rapid drop in NP levels. Knowing a patient's NP levels might thus assist with hemodynamic assessment and subsequent treatment titration. Monitoring NP levels in the outpatient setting might also improve patient care and outcomes.

Topics: Atrial Natriuretic Factor; Cardiovascular Diseases; Death, Sudden, Cardiac; Heart Diseases; Heart Failure; Hemodynamics; Humans; Kidney Failure, Chronic; Monitoring, Physiologic; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Obesity; Peptide Fragments; Prognosis; Pulmonary Edema; Pulmonary Embolism; Pulmonary Wedge Pressure; Renal Dialysis; Stroke; Weight Loss

The fact that the heart is able to secrete hormones, which are released in significant amounts in advance of certain cardiac conditions, has resulted in a wide range of opportunities and raised a multitude of questions. These hormones, named natriuretic peptides, possess diuretic, natriuretic and vasodilatory properties. The ones used in daily clinical practice are atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and their N-terminal fragments NT-proANP and NT-proBNP, respectively. Although most studies currently involve the use of BNP, the number involving NT-proBNP is expected to increase substantially in coming years because its level is less variable and its half-life longer. Nevertheless, at present there appears to be sufficient evidence to suggest that the plasma levels of these hormones will be extremely useful for the diagnosis, prognosis, screening, pharmacological monitoring, and treatment of patients with heart failure.

Topics: Atrial Natriuretic Factor; Biomarkers; Death, Sudden, Cardiac; Heart Failure; Hospitalization; Humans; Lung Diseases; Myocardium; Natriuretic Agents; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Natriuretic Peptides; Obesity; Prognosis; Renal Insufficiency; Ventricular Dysfunction, Left

In normal and obese humans, lipid mobilization and systemic nonesterified fatty acid levels are thought to be acutely controlled by catecholamines (ie, epinephrine and norepinephrine) and insulin. Natriuretic peptides (NPs) are known to play a key role in the regulation of salt and water balance and blood pressure homeostasis. They are involved in the pathophysiology of hypertension and heart failure. NPs have recently been found to exert potent lipolytic effects (ie, activating the breakdown of stored triacylglycerols) in isolated human fat cells and to promote lipid mobilization in vivo. Atrial natriuretic peptide increases the intracellular 3', 5'-cyclic guanosine monophosphate (cGMP) concentration which activates cGMP-dependent protein kinase leading to perilipin and hormone-sensitive lipase phosphorylation and lipolysis. NPs promote lipid mobilization when administered intravenously. NPs are also responsible for the residual lipid-mobilizing action observed under oral beta-blockade in subjects performing physical exercise. NPs are therefore novel factors which may open promising research pathways to explain the control of lipid mobilization in physiological and pathological conditions. The metabolic impact of altered production and circulation of NPs remains to be established. The potential influence of NPs on the development of lipid disorders, obesity-related cardiovascular events, and cardiac cachexia will be discussed in this review.

Topics: Atrial Natriuretic Factor; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Humans; Lipid Metabolism; Lipolysis; Metabolic Syndrome; Obesity

Topics: Animals; Atrial Natriuretic Factor; Catecholamines; Fatty Acids, Nonesterified; Humans; Lipolysis; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Obesity

Excessive accumulation of adipose tissue is associated with profound alterations in the cardiovascular system. including an increase in systemic blood pressure. It now appears clear that a central feature of obesity-associated hypertension is related to changes in sodium handling that may result from abnormalities in sympathetic nervous system activity, the renin-angiotensin-aldosterone system, natriuretic peptides, and kidney function. In this paper we review the role of these factors in the development of obesity-associated hypertension, thereby focusing on the potential role of adipose tissue in these alterations.

Topics: Adipose Tissue; Atrial Natriuretic Factor; Hypertension; Models, Biological; Obesity; Renin-Angiotensin System; Research Personnel; Sodium

The natriuretic peptide hormones play an important role in salt and blood pressure regulation. In observational studies, obesity and insulin resistance have been consistently associated with lower concentrations of natriuretic peptides. It has been proposed that insulin influences natriuretic peptide production.. We sought to determine the acute effects of insulin administration on natriuretic peptide concentrations.. 31 men and women (11 lean, 10 overweight, and 10 obese), ages 30-70 years, without cardiovascular disease or overt diabetes underwent a hyperinsulinemic-euglycemic insulin clamp. Plasma concentrations of N-terminal pro atrial natriuretic peptide (NT-proANP) and N-terminal pro B-type natriuretic peptide (NT-proBNP) were measured at baseline and steady-state (the final 30 minutes of the clamp protocol).. From baseline to steady-state, insulin levels increased from a mean level of 9.5 to 176.7 μU/ml (p<0.001). Over this period, circulating NT-proANP concentrations decreased by 9% (-1933 ng/L, p = 0.01). The changes in NT-proANP did not differ between lean, overweight, and obese individuals. Steady-state NT-proANP levels, adjusted for baseline, were lower in individuals with greater insulin resistance, independent of BMI. In contrast to NT-proANP, NT-proBNP levels did not change significantly during the clamp (p = 0.41).. Insulin administration was associated with a moderate decrease in circulating NT-proANP, but not NT-proBNP. The lowest NT-proANP concentrations were found in insulin-resistant individuals. Further investigations are warranted to elucidate potential mechanisms underlying the effects of insulin on the cardiac hormonal axis.

Topics: Adult; Aged; Atrial Natriuretic Factor; Female; Glucose Clamp Technique; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Peptide Fragments

In view of the known vasodilatory effects of glucagon-like peptide-1 and exenatide, we investigated the effects of exenatide on vasoactive factors. We analysed blood samples and mononuclear cells (MNCs) from a previous study, collected after a single dose and 12 weeks of exenatide or placebo treatment in a series of 24 patients with type 2 diabetes mellitus. After exenatide treatment, plasma concentrations of atrial natriuretic peptide, cyclic guanyl monophosphate (cGMP) and cyclic adenyl monophosphate increased significantly at 12 weeks. Plasma cGMP and adenylate cyclase expression in MNCs increased significantly after a single dose. Angiotensinogen concentration fell significantly 2 hours after a single dose and at 12 weeks, while renin and angiotensin II levels fell significantly only after a single dose and not after 12 weeks of treatment. Exenatide also suppressed the plasma concentration of transforming growth factor-β and the expression of P311 in MNCs at 12 weeks. Thus, exenatide induces an increase in a series of vasodilators, while suppressing the renin-angiotensin system. These changes may contribute to the overall vasodilatory effect of exenatide.

Topics: Adenylyl Cyclases; Angiotensinogen; Anti-Obesity Agents; Antihypertensive Agents; Atrial Natriuretic Factor; Blood Pressure; Cyclic AMP; Cyclic GMP; Diabetes Mellitus, Type 2; Exenatide; Gene Expression Regulation; Glucagon-Like Peptide 1; Humans; Hypoglycemic Agents; Leukocytes, Mononuclear; Nerve Tissue Proteins; Obesity; Oncogene Proteins; Peptides; Renin-Angiotensin System; Reproducibility of Results; Single-Blind Method; Transforming Growth Factor beta; Venoms

In weight loss trials, a considerable inter-individual variability in reduction of fat mass and changes of insulin resistance is observed, even under standardized study conditions. The underlying mechanisms are not well understood. Given the metabolic properties of the atrial natriuretic peptide (ANP) system, we hypothesized that ANP signaling might be involved in this phenomenon by changes of ANP secretion or receptor balance. Therefore, we investigated the impact of systemic, adipose and myocellular ANP system on metabolic and anthropometric improvements during weight loss.. We comprehensively investigated 143 subjects (31 male, 112 female) before and after a 3 month-standardized weight loss program. The time course of BMI, fat mass, insulin sensitivity, circulating mid-regional proANP (MR-proANP) levels as well as adipose and myocellular natriuretic receptor A (NPR-A) and C (NPR-C) mRNA expression were investigated.. BMI decreased by -12.6±3.7%. This was accompanied by a remarkable decrease of adipose NPR-C expression (1005.0±488.4 vs. 556.7±465.6; p<0.001) as well as a tendency towards increased adipose NPR-A expression (4644.7±946.8 vs. 4877.6±869.8; p=0.051). Weight loss induced changes in NPR-C (ΔNPR-C) was linked to relative reduction of total fat mass (ΔFM) (r=0.281; p<0.05), reduction of BMI (r=0.277; p<0.01), and increase of free fatty acids (ΔFFA) (r=-0.258; p<0.05). Basal NPR-C expression and weight loss induced ΔNPR-C independently explained 22.7% of ΔFM. In addition, ΔMR-proANP was independently associated with improvement of insulin sensitivity (standardized ß=0.246, p<0.01).. ANP receptor expression predicted the degree of weight loss induced fat mass reduction. Our comprehensive human data support that peripheral ANP signalling is involved in control of adipose tissue plasticity and function during weight loss. (Funded by the Deutsche Forschungsgemeinschaft (KFO281/2), the Berlin Institute of Health (BIH) and the German Centre for Cardiovascular Research (DZHK/BMBF); ClinicalTrials.gov number: NCT00850629).

Topics: Adipose Tissue; Adiposity; Adult; Atrial Natriuretic Factor; Blood Glucose; Body Mass Index; Caloric Restriction; Counseling; Exercise Therapy; Female; Humans; Insulin; Insulin Resistance; Lipids; Male; Middle Aged; Obesity; Overweight; Receptors, Atrial Natriuretic Factor; Weight Loss; Weight Reduction Programs

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

Atrial natriuretic peptides (ANP) and Brain natriuretic peptides (BNP) stimulate fat cell plasma membrane receptors. They are potent lipolytic agents on isolated fat cells from subcutaneous adipose tissue. The physiological effects of continuous endurance exercise on ANP release and plasma free fatty acids (FFA) concentrations have been well described. The enhancement of fat metabolism using high intensity intermittent exercise protocols has been assessed in more recent investigations. The combined effects of endurance exercise and water immersion on ANP and FFA plasma concentration and the magnitude of excess post-exercise oxygen consumption (EPOC) might be further enhanced by choosing the most effective exercise protocol. Exercise modalities may play a significant role in the future prevention and treatment of obesity.. The two testing trials will be performed according to a randomized and cross-over design. Twenty healthy sedentary pre-obese and obese class-1 men will be scrutinized with regard to their metabolic responses to continuous exercise in water and to high intensity endurance exercise in water. Both trials will be matched for energy expenditure. After preliminary testing, the tests will be conducted as repeated measurements. The two different exercise protocols will be compared. The aims of the study are to investigate (1) whether continuous endurance exercise or high intensity intermittent endurance exercise in water elicits both a higher release of ANP and BNP and a higher plasma concentration of glycerol and (2) to determine whether continuous endurance exercise in water or a high intensity intermittent endurance exercise in water would lead to a more pronounced short term (two hours) EPOC effect.. If our hypothesis would be confirmed, the most effective exercise protocol based on the combined effects of high intensity endurance exercise and water immersion on ANP and BNP release and glycerol plasma concentrations can be identified. Moreover, the magnitude of the EPOC effect can be augmented. Our study would provide a major contribution for creating optimized exercise modalities in the prevention and treatment of obesity.. Current controlled trials, ISRCTN95488515.

Topics: Atrial Natriuretic Factor; Biomarkers; Cross-Over Studies; Exercise Therapy; Fatty Acids, Nonesterified; Glycerol; Humans; Hydrotherapy; Immersion; Male; Natriuretic Peptide, Brain; Obesity; Physical Endurance; Research Design; Sedentary Behavior; Switzerland; Time Factors; Treatment Outcome; Up-Regulation; Water

The aim was to investigate the impact of polycystic ovary syndrome (PCOS) on the regulation of lipolysis by catecholamine and for the first time atrial natriuretic peptide (ANP) before and after 16 wk of aerobic training.. Eight hyperandrogenic obese women with PCOS [age, 25 +/- 1 yr; body mass index (BMI), 32.0 +/- 1.6 kg/m(2)] and seven healthy BMI-matched controls participated. Studies were performed before and after a 16-wk exercise training program in women with PCOS and cross-sectionally in a group of BMI-matched controls.. Lipolysis was measured in vitro in isolated adipocytes and in vivo by microdialysis of sc abdominal adipose tissue before and during a hyperinsulinemic euglycemic clamp.. In vitro, baseline and maximal ANP- and isoproterenol-induced lipolysis was markedly reduced in PCOS women. Baseline (P < 0.001) and ANP-(P < 0.01) and isoproterenol-(P < 0.001) mediated lipolysis, however, was remarkably increased after training, independent of changes in body weight and sex hormones. These functional improvements were supported by an increased 1) lipolytic sensitivity for ANP (1.3-fold; P < 0.05); 2) lipolytic responsiveness for isoproterenol (1.7-fold; P < 0.01); and 3) postreceptor-acting agent dibutyryl-cAMP (activating cAMP-dependent protein kinase) (2.1-fold; P < 0.05). In vivo, the lipolytic responsiveness to isoproterenol was also reduced in PCOS and tended to increase after exercise training. The insulin suppression of lipolysis during the hyperinsulinemic euglycemic clamp was also reduced in PCOS.. Together, these data show that the regulation of lipolysis by the main endocrine hormones is impaired in women with PCOS. These lipolytic defects can be partly reversed by aerobic exercise training independent of changes in body fat mass and sex hormones.

Topics: Adult; Atrial Natriuretic Factor; Body Mass Index; Catecholamines; Exercise; Exercise Therapy; Female; Glucose Clamp Technique; Humans; Insulin; Isoproterenol; Lipolysis; Microdialysis; Obesity; Polycystic Ovary Syndrome; Young Adult

Hemodynamic mechanism for brain edema forrmation in patients with hypertensive encephalopathy is unclear. Potential roles of natriuretic peptides in the pathogenesis of hypertensive encephalopathy are discussed. A 32-year-old man presented with slight left hemiparesis. He was slightly confused, and his blood pressure was extremely high. Cranial plain computerized tomography scans revealed diffuse brain edema mainly in the supratentorial white matter region. Blood examination revealed that plasma concentrations of atrial and brain natriuretic peptides were significantly high. His left hemiparesis disappeared within a day, but he tended to be agitated. His altered mental status, however, resolved with control of blood pressure. Serial magnetic resonance imagings demonstrated that the magnitude of brain edema was attenuated in proportion to decline in plasma concentrations of natriuretic peptides. This case suggests that significant elevation of plasma concentrations of natriuretic peptides may contribute to an acute rise in blood pressure, and that these peptides potentially play an important role in development of brain edema in hypertensive encephalopathy.

Topics: Adult; Atrial Natriuretic Factor; Blood Pressure; Brain; Brain Injuries; Humans; Hypertensive Encephalopathy; Magnetic Resonance Imaging; Male; Natriuretic Peptide, Brain; Obesity; Radiography; Renin-Angiotensin System; Time Factors

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

Obesity increases the risk of developing hypertension by two-to fourfold, with more that one third of all cases of hypertension attributable to obesity. The present study tested the role of atrial natriuretic peptide (ANP), endothelin-1,2 (ET-1,2) and neuropeptide Y (NPY) in pathogenesis of obesity hypertension. The plasma concentrations of ANP, ET-1,2 and NPY were determined in the peripheral venous blood by radioimmunoassay in 27 obese hypertensive patients (group I), in 24 obese normotensive patients (group II), and in 35 normal subjects (group III).. Mean plasma ANP was significantly higher in obese than in normal subjects. ANP levels were higher in patients group I than in those group II and I. In patients of group I plasma ANP concentrations correlated with III BMI and mean blood pressure. Plasma levels of ET-1,2 and NPY were similar in patients group I, II and III.

Topics: Adolescent; Adult; Aged; Atrial Natriuretic Factor; Catecholamines; Endothelin-1; Endothelin-2; Humans; Hypertension; Male; Middle Aged; Neuropeptide Y; Obesity; Peptides

Low concentrations of natriuretic peptides (NPs) have been associated with greater risk for Type 2 diabetes (T2D). African American individuals (AA) have lower NP levels and are disproportionately burdened by T2D. The purpose of this study was to test the hypothesis that higher post-challenge insulin in AA adults is associated with lower plasma N-terminal pro-atrial natriuretic peptide (NT-proANP). A secondary purpose was to explore associations between NT-proANP and adipose depots. Participants were 112 AA and European American (EA) adult men and women. Measures of insulin were obtained from an oral glucose tolerance test and hyperinsulinemic-euglycemic glucose clamp. Total and regional adipose depots were measured from DXA and MRI. Multiple linear regression analysis was used to assess associations of NT-proANP with measures of insulin and adipose depots. Lower NT-proANP concentrations in AA participants was not independent of 30-min insulin area under the curve (AUC). NT-proANP was inversely associated with 30-min insulin AUC in AA participants, and with fasting insulin and HOMA-IR in EA participants. Thigh subcutaneous adipose tissue and perimuscular adipose tissue were positively associated with NT-proANP in EA participants. Higher post-challenge insulin may contribute to lower ANP concentrations in AA adults.

Topics: Adult; Atrial Natriuretic Factor; Biomarkers; Diabetes Mellitus, Type 2; Female; Humans; Insulin; Male; Natriuretic Peptides; Obesity; Peptide Fragments

Atrial natriuretic peptide plays a potential role in obesity with unclear molecular mechanisms. The objective of this study was to examine the association between its coding gene (natriuretic peptide A [NPPA]) methylation and obesity.. Peripheral blood DNA methylation of NPPA promoter was quantified at baseline by targeted bisulfite sequencing for 2,497 community members (mean aged 53 years, 38% men) in the Gusu cohort. Obesity was repeatedly assessed by body mass index (BMI) and waist circumference (WC) at baseline and follow-up examinations. The cross-sectional, longitudinal, and prospective associations between NPPA promoter methylation and obesity were examined.. Of the 9 CpG loci assayed, DNA methylation levels at 6 CpGs were significantly lower in participants with central obesity than those without (all p < 0.05 for permutation test). These CpG methylation levels at baseline were also inversely associated with dynamic changes in BMI or WC during follow-up (all p < 0.05 for permutation test). After an average 4 years of follow-up, hypermethylation at the 6 CpGs (CpG2 located at Chr1:11908348, CpG3 located at Chr1:11908299, CpG4 located at Chr1:11908200, CpG5 located at Chr1:11908182, CpG6 located at Chr1:11908178, and CpG8 located at Chr1:11908165) was significantly associated with a lower risk of incident central obesity (all p < 0.05 for permutation test).. Hypomethylation at NPPA promoter was associated with increased future risk of central obesity in Chinese adults. Aberrant DNA methylation of the NPPA gene may participate in the mechanisms of central obesity.

Topics: Atrial Natriuretic Factor; Body Mass Index; China; Cross-Sectional Studies; DNA Methylation; Female; Humans; Longitudinal Studies; Male; Middle Aged; Obesity; Obesity, Abdominal; Procainamide

Topics: Acetates; Animals; Atrial Natriuretic Factor; Diet, High-Fat; Male; Natriuretic Peptide, Brain; Obesity; Rats; Rats, Wistar

Increasing evidence suggests natriuretic peptides (NPs) coordinate interorgan metabolic crosstalk. We recently reported exogenous ANP treatment ameliorated systemic insulin resistance by inducing adipose tissue browning and attenuating hepatic steatosis in diet-induced obesity (DIO). We herein investigated whether ANP treatment also ameliorates myocardial insulin resistance, leading to cardioprotection during ischemia-reperfusion injury (IRI) in DIO. Mice fed a high-fat diet (HFD) or normal-fat diet for 13 weeks were treated with or without ANP infusion subcutaneously for another 3 weeks. Left ventricular BNP expression was substantially reduced in HFD hearts. Intraperitoneal-insulin-administration-induced Akt phosphorylation was impaired in HFD hearts, which was restored by ANP treatment, suggesting that ANP treatment ameliorated myocardial insulin resistance. After ischemia-reperfusion using the Langendorff model, HFD impaired cardiac functional recovery with a corresponding increased infarct size. However, ANP treatment improved functional recovery and reduced injury while restoring impaired IRI-induced Akt phosphorylation in HFD hearts. Myocardial ultrastructural analyses showed increased peri-mitochondrial lipid droplets with concomitantly decreased ATGL and HSL phosphorylation levels in ANP-treated HFD, suggesting that ANP protects mitochondria from lipid overload by trapping lipids. Accordingly, ANP treatment attenuated mitochondria cristae disruption after IRI in HFD hearts. In summary, exogenous ANP treatment ameliorates myocardial insulin resistance and protects against IRI associated with mitochondrial ultrastructure modifications in DIO. Replenishing biologically active NPs substantially affects HFD hearts in which endogenous NP production is impaired.

Topics: Animals; Atrial Natriuretic Factor; Diet, High-Fat; Insulin Resistance; Mice; Myocardial Reperfusion Injury; Obesity; Proto-Oncogene Proteins c-akt

The causal relationship between obesity and high blood pressure is established; however, the detailed pathways for such association are still under research. This work aims to assess the changes in neprilysin, vasoconstrictor and vasodilatory molecules in obese hypertensive patients undergoing laparoscopic sleeve gastrectomy (LSG).. The present prospective study was done on 59 hypertensive obese patients in whom LGS was performed. Blood pressure, as well as blood samples for neprilysin, angiotensinogen, angiotensin II, renin, endothelin-1 "ET-1", aldosterone, atrial natriuretic peptide "ANP" and B-type natriuretic peptide "BNP", were assessed before and 15 months after surgery. Patients were divided into two groups according to the remission of hypertension (HTN).. After 15 months, remission of hypertension was seen in 42 patients (71%). The declines in the following measurements were significantly higher in patients with remission than those with persistent HTN: aldosterone (p = .029567), angiotensin II (p < .000001), angiotensinogen (p = .000021), neprilysin (p = .000601), renin (p = .000454) and endothelin-1(p = .000030). There was a significantly higher increment in ANP (p = .000002) and a non-significant increment in BNP (p = .081740). Angiotensin II 15 months after LSG and Δ ANP % were significant independent predictors of persistent HTN.. In the setting of LSG, aldosterone, angiotensinogen, angiotensin II, renin and neprilysin were significantly lower in patients with remission of HTN after 15 months than those with persistent HTN, and natriuretic peptides were significantly higher. A lower postoperative level of angiotensin II and a larger percentage increment of ANP are independently associated with hypertension remission after LSG.

Topics: Atrial Natriuretic Factor; Gastrectomy; Humans; Hypertension; Laparoscopy; Obesity; Prospective Studies

Topics: Atrial Natriuretic Factor; Blood Pressure; Humans; Hypertension; Obesity

Topics: Adult; Aged; Atrial Natriuretic Factor; Glucose; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Male; Middle Aged; Obesity; Thinness

A plethora of studies have demonstrated that cardiomyopathy represents a serious source of morbidity and mortality in patients with diabetes. Yet, the underlying mechanisms of diabetic cardiomyopathy are still poorly understood. Of interest, cytochrome P450 2J (CYP2J) and soluble epoxide hydrolase (sEH) are known to control the maintenance of cardiovascular health through the regulation of cardioprotective epoxyeicosatrienoic acids (EETs) and its less active products, dihydroxyeicosatrienoic acids (DHETs). Therefore, we examined the role of the aforementioned pathway in the development of diabetic cardiomyopathy. Our diabetic model initiated cardiomyopathy as indexed by the increase in the expression of hypertrophic markers such as NPPA. Furthermore, diabetic cardiomyopathy was associated with a low level of cardiac EETs and an increase of the DHETs/EETs ratio both in vivo and in cardiac cells. The modulation in EETs and DHETs was attributed to the increase of sEH and the decrease of CYP2J. Interestingly, the reduction of sEH attenuates cardiotoxicity mediated by high glucose in cardiac cells. Mechanistically, the beneficial effect of sEH reduction might be due to the decrease of phosphorylated ERK1/2 and p38. Overall, the present work provides evidence that diabetes initiates cardiomyopathy through the increase in sEH, the reduction of CYP2J, and the decrease of cardioprotective EETs.

Topics: Animals; Atrial Natriuretic Factor; Blood Glucose; Cell Line; Cytochrome P-450 Enzyme System; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Diet, High-Fat; Eicosanoids; Epoxide Hydrolases; Extracellular Signal-Regulated MAP Kinases; Humans; Male; Mice, Inbred C57BL; Myocytes, Cardiac; Natriuretic Peptide, Brain; Obesity; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Signal Transduction; Streptozocin

The sodium-sparing effect of insulin leads to increase in total sodium pool of the body which is a chronic stimulus for atrial natriuretic peptide (ANP). In our study we aimed to determine the relationship between ANP and microvascular complications of diabetes.. 60 patients, 30-70 years old, with the diagnosis of type 2 diabetes mellitus (DM) are enrolled into the study. Patients with a chronic disease other than DM are excluded. Blood samples for routine biochemical tests are taken after at least 12 h fasting at 8-9 am. Blood samples for glucose and insulin levels are taken 2 h after a standard meal. Blood tubes with EDTA are used for ANP levels. The microvascular complications of the patients are evaluated.. 32 of the patients had microvascular complications. Age, BMI, waist and hip circumferences, and ANP levels were significantly higher in the group with microvascular complications. There were no significant differences in waist-to-hip ratio, blood glucose, HbA1c, fasting insulin, postprandial insulin, fasting HOMA, postprandial HOMA as well as sodium, potassium, magnesium, calcium and lipid levels between the two groups. When the relationship between ANP and obesity, retinopathy, neuropathy, nephropathy, diabetes time, HbA1c, or sex are evaluated separately, the only significant parameters related to ANP were obesity and retinopathy.. In our study we have found that there was a significant relationship between ANP levels and microvascular complications of diabetes. Future studies are needed to show if ANP is the stimulus of microvascular complication development/progression or only an epiphenomenon.

Topics: Adult; Aged; Aryldialkylphosphatase; Atrial Natriuretic Factor; Biomarkers; Blood Glucose; Brachial Artery; Cohort Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Humans; Insulin; Male; Middle Aged; Obesity; Organ Size; Tunica Intima

Obese persons have lower circulating natriuretic peptide (NP) concentrations. It has been proposed that this natriuretic handicap plays a role in obesity-related hypertension. In contrast, hypertensive patients with left atrial enlargement have higher circulating NP concentrations. On this background, we investigated whether obese hypertensive men could have lower circulating NP concentrations despite evidence of pressure-induced greater left atrial size.. We examined 98 obese men (body mass index [BMI] ≥ 30.0 kg/m2) and 27 lean normotensive men (BMI 20.0-24.9 kg/m2). All men were healthy, medication free, with normal left ventricular ejection fraction. We measured blood pressure using 24-hour ambulatory blood pressure (ABP) recordings. Hypertension was defined as 24-hour ABP ≥ 130/80 mm Hg, and normotension was defined as 24-hour ABP < 130/80 mm Hg. We determined left atrial size using echocardiography, and we measured fasting serum concentrations of midregional proatrial NP (MR-proANP).. Of the 98 obese men, 62 had hypertension and 36 were normotensive. The obese hypertensive men had greater left atrial size (mean ± SD: 28.7 ± 6.0 ml/m2) compared with the lean normotensive men (23.5 ± 4.5 ml/m2) and the obese normotensive men (22.7 ± 5.1 ml/m2), P < 0.01. Nevertheless, despite evidence of pressure-induced greater left atrial size, the obese hypertensive men had lower serum MR-proANP concentrations (median [interquartile range]: 48.5 [37.0-64.7] pmol/l) compared with the lean normotensive men (69.3 [54.3-82.9] pmol/l), P < 0.01, whereas the obese normotensive men had serum MR-proANP concentrations in between the 2 other groups (54.1 [43.6-62.9] pmol/l).. Despite greater left atrial size, obese hypertensive men have lower circulating MR-proANP concentrations compared with lean normotensive men.

Topics: Adult; Aged; Atrial Natriuretic Factor; Blood Pressure; Cross-Sectional Studies; Echocardiography; Heart Atria; Hemodynamics; Humans; Hypertension; Male; Middle Aged; Obesity

The cardiac hormones atrial (ANP) and B-type natriuretic peptides (BNP) moderate arterial blood pressure and improve energy metabolism as well as insulin sensitivity via their shared cGMP-producing guanylyl cyclase-A (GC-A) receptor. Obesity is associated with impaired NP/GC-A/cGMP signaling, which possibly contributes to the development of type 2 diabetes and its cardiometabolic complications. In vitro, synthetic ANP, via GC-A, stimulates glucose-dependent insulin release from cultured pancreatic islets and β-cell proliferation. However, the relevance for systemic glucose homeostasis in vivo is not known. To dissect whether the endogenous cardiac hormones modulate the secretory function and/or proliferation of β-cells under (patho)physiological conditions in vivo, here we generated a novel genetic mouse model with selective disruption of the GC-A receptor in β-cells.. Mice with a floxed GC-A gene were bred to Rip-Cre. In vitro, the insulinotropic and proliferative actions of ANP were abolished in islets isolated from β GC-A KO mice. Concordantly, in vivo, infusion of BNP mildly enhanced baseline plasma insulin levels and glucose-induced insulin secretion in control mice. This effect of exogenous BNP was abolished in β GC-A KO mice, corroborating the efficient inactivation of the GC-A receptor in β-cells. Despite this under physiological, ND conditions, fasted and fed insulin levels, glucose-induced insulin secretion, glucose tolerance and β-cell morphology were similar in β GC-A KO mice and control littermates. However, HFD-fed β GC-A KO animals had accelerated glucose intolerance and diminished adaptative β-cell proliferation.. Our studies of β GC-A KO mice demonstrate that the cardiac hormones ANP and BNP do not modulate β-cell's growth and secretory functions under physiological, normal dietary conditions. However, endogenous NP/GC-A signaling improves the initial adaptative response of β-cells to HFD-induced obesity. Impaired β-cell NP/GC-A signaling in obese individuals might contribute to the development of type 2 diabetes.

Topics: Animals; Atrial Natriuretic Factor; Blood Glucose; Cell Proliferation; Disease Models, Animal; Disease Progression; Gene Deletion; Genetic Predisposition to Disease; Glucose Intolerance; Insulin; Insulin-Secreting Cells; Mice, Knockout; Natriuretic Peptide, Brain; Obesity; Phenotype; Receptors, Atrial Natriuretic Factor; Signal Transduction; Tissue Culture Techniques

To investigate the relationships among aldosterone level, use of antihypertensive (anti-HTN) medications, clinical profile, and atrial natriuretic peptide (ANP) level in individuals with HTN.. In a community-based cohort, we analyzed aldosterone plasma levels based on the presence (n=477) or absence (n=1073) of HTN. In individuals with HTN, we evaluated circulating aldosterone levels according to the number of anti-HTN drugs used, analyzed the associated clinical characteristics, and determined the relationship to the counterregulatory cardiac hormone ANP. Data were collected from August 25, 1997, through September 5, 2000.. Participants with HTN had higher serum aldosterone levels than those without HTN (6.4 vs 4.1 ng/dL [to convert to pmol/L, multiply by 27.74]; P<.001). When individuals with HTN were stratified according to the number of anti-HTN medications used, the increase in number of medications (0, 1, 2, and ≥3) was associated with higher aldosterone levels (4.8, 6.4, 7.10, and 7.9 ng/dL, respectively; P=.002), worse metabolic profile, and higher prevalence of cardiovascular, renal, and metabolic disease. In participants with HTN, ANP plasma levels were inversely related to aldosterone levels when the latter was divided into tertiles.. In this randomly selected general population cohort, aldosterone levels were higher in individuals with HTN compared with normotensive participants. Aldosterone levels increased with anti-HTN medication use. These findings also suggest a relative ANP deficiency with increasing aldosterone levels and anti-HTN drug use. These studies have pathophysiologic and therapeutic implications for targeting aldosterone in the clinical treatment of HTN.

Topics: Aged; Aldosterone; Antihypertensive Agents; Atrial Natriuretic Factor; Blood Glucose; Cholesterol, LDL; Cohort Studies; Coronary Artery Disease; Diuretics; Female; Glomerular Filtration Rate; Heart Failure; Humans; Hypertension; Hypertrophy, Left Ventricular; Hypolipidemic Agents; Insulin; Male; Metabolic Syndrome; Middle Aged; Minnesota; Myocardial Infarction; Obesity; Sampling Studies; Stroke; Triglycerides

In whites, the minor G allele of the atrial natriuretic peptide (ANP) genetic variant rs5068 is associated with higher circulating levels of ANP and B-type natriuretic peptide (BNP), lower risk of hypertension, higher high-density lipoprotein (HDL) cholesterol plasma levels, and lower prevalence of obesity and metabolic syndrome. The observed phenotype is consistent with the blood pressure lowering and metabolic properties of ANP and BNP. The cardiovascular and metabolic phenotype associated with rs5068 genotypes in African Americans is undefined. We genotyped 1631 African Americans in the Multi-Ethnic Study of Atherosclerosis (MESA) for rs5068 and investigated their phenotype. Genotype frequencies of rs5068 were 93.2% AA (n = 1520), 6.7% AG (n = 110) and 0.1% GG (n = 1). All subsequent analyses are AG + GG versus AA genotype. Using a Bonferroni corrected level of significance of 0.005, the prevalence of metabolic syndrome (23% vs 38%, age-sex-adjusted p = 0.002) and triglycerides plasma values (76 vs 90 mg/dl, age-sex-BMI adjusted p = 0.004) were both significantly lower in the AG+GG genotypes. In the AG+GG genotypes, the prevalence of diabetes (8% vs 18%, age-sex-BMI-adjusted p = 0.02) and insulin plasma levels tended to be lower (4.8 vs 5.7 μU/ml, age-sex-BMI adjusted p = 0.04) whereas HDL-cholesterol levels tended to be higher (55 vs 50 mg/dl, age-sex-BMI-adjusted p = 0.04). No association was found with hypertension. The association between the rs5068 G allele and a favorable metabolic phenotype is now shown in African Americans. The rs5068 AG+GG genotypes are associated with lower prevalence of metabolic syndrome and lower triglycerides values.

Topics: Aged; Aged, 80 and over; Alleles; Atherosclerosis; Atrial Natriuretic Factor; Black or African American; Cardiovascular Diseases; Cardiovascular System; Cholesterol, HDL; Cohort Studies; Ethnicity; Female; Genotype; Geography; Humans; Insulin; Male; Metabolic Syndrome; Middle Aged; Natriuretic Peptide, Brain; Obesity; Phenotype; Prevalence; Triglycerides; United States

Obese persons have low circulating natriuretic peptide (NP) concentrations. It has been proposed that this 'natriuretic handicap' could play a role in obesity-related hypertension. The normal physiological response of the NP system to an increase in blood pressure (BP) is an increase in NP secretion with concomitant higher circulating NP concentrations. In this study, we investigated whether higher BP would also be related to higher circulating NP concentrations in obese men; furthermore, we verified that BP had affected the hearts of our study participants, by determining left ventricular mass (LVM).. We examined 103 obese healthy medication-free men. We measured 24-hour ambulatory BP (ABP). LVM was calculated using the Cornell voltage-duration product method. Fasting serum concentrations of midregional proatrial NP (MR-proANP), a surrogate for active ANP, were measured. Linear regression analysis was used to calculate age-adjusted standardised regression coefficients (β).. LVM and BP increased across systolic ABP quartiles (mean LVM±SD: 1599.1±387.2 mm ms in first vs 2188.5±551.3 mm ms in fourth quartile, p<0.001; mean systolic ABP±SD: 114.5±4.2 mm Hg in first vs 149.0±7.7 mm Hg in fourth quartile, p<0.001). Systolic ABP was robustly associated with LVM (ß=0.48, p<0.001). Despite evidence of BP-related increases in LVM, serum MR-proANP was negatively associated with systolic ABP (ß=-0.32, p=0.004) and with diastolic ABP (ß=-0.45, p<0.001).. Contrary to known physiological BP responses, MR-proANP was negatively associated with ABP in our study. This suggests that a low amount of circulating NPs could play a role in the early stage of obesity-related hypertension.

Topics: Adult; Aged; Atrial Natriuretic Factor; Biomarkers; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Female; Heart Ventricles; Humans; Hypertension; Male; Middle Aged; Obesity

To evaluate left atrial (LA) volume and functions in obese subjects using real time three-dimensional echocardiography (RT3DE) and also the relationship between LA mechanical functions and N-terminal pro-atrial natriuretic peptide (NT-proANP).. This study included 40 obese (26 females and 14 males, mean age 51.9 years) and 40 normal weight subjects (23 females and 16 males, mean age 53.5 years) with normal coronary angiograms. All the study participants underwent RT3DE to assess LA volume and mechanical function. Plasma NT-proANP was determined by ELISA method.. There was no significant difference between groups in left ventricular (LV) diameters and ejection fraction, which reflect LV systolic function. However, transmitral deceleration time, isovolumetric relaxation time, and peak late diastolic tissue Doppler velocity values, which reflect LV diastolic function, were found to be significantly higher in obese subjects when compared with controls. LA maximum volume (LAVmax), LAVmax index (LAVI), LA minimal volume (LAVmin), before atrial contraction volume (LAVpreA), LA active emptying volume, LA total emptying volume, and LA active emptying fraction, which reflect LA reservoir and pump functions, were also higher in obese subjects when compared with controls. LA passive emptying fraction was significantly lower in obese subjects than in controls. NT-proANP levels were similar between groups. There were positive correlations between NT-proANP level and LAVI, LAVmax, LAVmin, LAVpreA, and LA total and active emptying volumes.. Left atrial mechanical functions and volumes are impaired in obese subjects. These findings may be regarded as early markers of subclinical cardiac failure in obese subjects who have not yet exhibited any clinical evidence of cardiovascular disease.

Topics: Atrial Natriuretic Factor; Echocardiography, Three-Dimensional; Enzyme-Linked Immunosorbent Assay; Female; Heart Atria; Heart Ventricles; Humans; Male; Middle Aged; Obesity; Protein Precursors; Ventricular Dysfunction, Left

Obesity is a risk factor for heart failure (HF) and identification of symptomatic, and obese HF patients are challenging, because obesity can mimic HF symptoms. We aimed to evaluate novel biomarkers for HF in obese subjects of the general population.. Midregional proadrenomedullin (MR-proADM), growth differentiation factor-15 (GDF-15), midregional pro-atrial natriuretic peptide (MR-proANP), and NT-proBNP were measured in 5000 individuals of the population-based Gutenberg Health Study (GHS), including 1204 obese individuals (BMI ≥ 30 kg/m. NT-proBNP and MR-proANP were lower in obese vs. non-obese HF individuals (p = 0.013 and p = 0.01, respectively), whereas GDF-15 was similar and MR-proADM was higher in obese vs. non-obese HF individuals. All biomarkers increased the odds ratio (OR) for prevalent HF. For NT-proBNP and MR-proANP, this increase was lower in obese vs. non-obese individuals, whereas it was comparable for MR-proADM and GDF-15. All biomarkers were associated with increased all-cause mortality (median follow-up 7.3 years, 211 events). Results were validated in 8373 individuals (n = 1734 with BMI ≥ 30 kg/m. All biomarkers were associated with HF and higher risk for all-cause mortality in the general population. In contrast to the natriuretic peptides NT-proBNP and MR-proANP, the novel biomarkers MR-proADM and GDF-15 were not lower in obese HF individuals, indicating their potential to facilitate HF diagnosis and prognosis in an increasingly obese HF population.

Topics: Adrenomedullin; Aged; Atrial Natriuretic Factor; Biomarkers; Cohort Studies; Female; Follow-Up Studies; Growth Differentiation Factor 15; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Prognosis; Prospective Studies; Protein Precursors; Risk Factors

Atrial fibrillation (AF) may present variously in time, and AF may progress from self-terminating to non-self-terminating AF, and is associated with impaired prognosis. However, predictors of AF types are largely unexplored. We investigate the clinical, biomarker, and genetic predictors of development of specific types of AF in a community-based cohort.. We included 8042 individuals (319 with incident AF) of the PREVEND study. Types of AF were compared, and multivariate multinomial regression analysis determined associations with specific types of AF.. Mean age was 48.5 ± 12.4 years and 50% were men. The types of incident AF were ascertained based on electrocardiograms; 103(32%) were classified as AF without 2-year recurrence, 158(50%) as self-terminating AF, and 58(18%) as non-self-terminating AF. With multivariate multinomial logistic regression analysis, advancing age (P< 0.001 for all three types) was associated with all AF types, male sex was associated with AF without 2-year recurrence and self-terminating AF (P= 0.031 and P= 0.008, respectively). Increasing body mass index and MR-proANP were associated with both self-terminating (P= 0.009 and P< 0.001) and non-self-terminating AF (P= 0.003 and P< 0.001). The only predictor associated with solely self-terminating AF is prescribed anti-hypertensive treatment (P= 0.019). The following predictors were associated with non-self-terminating AF; lower heart rate (P= 0.018), lipid-lowering treatment prescribed (P= 0.009), and eGFR <60 mL/min/1.73 m2 (P= 0.006). Three known AF-genetic variants (rs6666258, rs6817105, and rs10821415) were associated with self-terminating AF.. We found clinical, biomarker and genetic predictors of specific types of incident AF in a community-based cohort. The genetic background seems to play a more important role than modifiable risk factors in self-terminating AF.

Topics: Adult; Age Factors; Albuminuria; Aminopeptidases; Antihypertensive Agents; Atrial Fibrillation; Atrial Natriuretic Factor; Blood Glucose; Body Mass Index; C-Reactive Protein; Cohort Studies; Creatinine; Cystatin C; Female; Genetic Predisposition to Disease; Glomerular Filtration Rate; Heart Rate; Homeobox Protein PITX2; Homeodomain Proteins; Humans; Hypertension; Hypolipidemic Agents; Logistic Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Phosphotransferases (Phosphate Group Acceptor); Polymorphism, Single Nucleotide; Risk Factors; Sex Factors; Small-Conductance Calcium-Activated Potassium Channels; Transcription Factors

Catecholamines and natriuretic peptides (NPs) are the only hormones with pronounced lipolytic effects in human white adipose tissue. Although catecholamine-induced lipolysis is well known to be impaired in obesity and insulin resistance, it is not known whether the effect of NPs is also altered.. Catecholamine- and atrial NP (ANP)-induced lipolysis was investigated in abdominal subcutaneous adipocytes in vitro and in situ by microdialysis.. In a cohort of 122 women, both catecholamine- and ANP-induced lipolysis in vitro was markedly attenuated in obesity (n=87), but normalized after substantial body weight loss (n=52). The impairment of lipolysis differed between the two hormones when expressing lipolysis per lipid weight, the ratio of stimulated over basal (spontaneous) lipolysis rate or per number of adipocytes. Thus, while the response to catecholamines was lower when expressed as the former two measures, it was higher when expressed per cell number, a consequence of the significantly larger fat cell size in obesity. In contrast, although ANP-induced lipolysis was also attenuated when expressed per lipid weight or the ratio stimulated/basal, it was similar between non-obese and obese subjects when expressed per cell number suggesting that the lipolytic effect of ANP may be even more sensitive to the effects of obesity than catecholamines. Obesity was characterized by a decrease in the protein expression of the signaling NP A receptor (NPRA) and a trend toward increased levels of the clearance receptor NPRC. The impairment in ANP-induced lipolysis observed in vitro was corroborated by microdialysis experiments in situ in a smaller cohort of lean and overweight men.. ANP- and catecholamine-induced lipolysis is reversibly attenuated in obesity. The pro-lipolytic effects of ANP are relatively more impaired compared with that of catecholamines, which may in part be due to specific changes in NP receptor expression.

Topics: Adipocytes; Adult; Atrial Natriuretic Factor; Blotting, Western; Catecholamines; Energy Metabolism; Female; Gene Expression Regulation; Humans; Lipolysis; Male; Microdialysis; Obesity; Subcutaneous Fat, Abdominal

The cardiac natriuretic peptides (NPs), atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), have central roles in sodium and blood pressure regulation. Extracardiac factors (e.g., obesity and diabetes) influence NP production, potentially altering cardiovascular responses to volume and pressure stress.. This study examined the effects of acute carbohydrate intake on the NP system in humans, and investigated underlying mechanisms.. Normotensive subjects (N = 33) were given a high-carbohydrate shake. Venous blood was sampled to measure N-terminal (NT)-proANP and NT-proBNP levels. Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and HepG2 cells were treated with glucose, and expression levels of NPs and micro ribonucleic acid 425 (miR-425), a negative regulator of ANP, were examined. The role of nuclear factor kappa B (NF-κB) in the glucose-mediated effects was investigated using a NF-κB inhibitor and expression plasmids encoding NF-κB subunits.. We observed a 27% reduction in the levels of circulating NT-proANP (p < 0.001, maximal at 6 h) after carbohydrate challenge, with no effect on NT-proBNP levels in our human subjects. Glucose treatment of hESC-CMs for 6 h and 24 h increased levels of the primary transcript of miR-425 (pri-miR-425) and mature miR-425. A corresponding decrease in NPPA messenger RNA levels was also observed at both time points. Overexpression of NF-κB subunits in H9c2 cardiomyocytes increased miR-425 levels, whereas inhibition of NF-κB abrogated the glucose-mediated increase in pri-miR-425 levels in HepG2 cells.. Acute carbohydrate challenge is associated with a reduction in ANP production. The mechanism appears to involve a glucose-induced increase in the expression of miR-425, mediated by NF-κB signaling.

Topics: Adult; Animals; Atrial Natriuretic Factor; Blood Pressure; Female; Gene Expression Regulation; Hep G2 Cells; Humans; Male; Mice; MicroRNAs; Myocytes, Cardiac; Natriuretic Peptide, Brain; Natriuretic Peptides; Obesity; Peptide Fragments; Protein Precursors; RNA, Messenger; Signal Transduction; Sodium

Catecholamines and atrial natriuretic peptide (ANP) are major regulators of adipocyte lipolysis. Although obesity is characterized by catecholamine resistance in subcutaneous adipose tissue (SCAT), data on ANP lipolytic response and sensitivity in different adipose tissue (AT) depots of metabolically distinct humans are scarce. Ex vivo catecholamine- and ANP-induced lipolysis was investigated in adipocytes derived from SCAT and visceral AT (VAT) depot of lean (n=13) and obese men, with (n=11) or without (n=18) type 2 diabetes (HbA1c < or ≥ 6.5%). Underlying molecular mechanisms were examined by looking at functional receptors in the NP signalling pathway at the mRNA and protein level. Maximal ANP- and catecholamine-induced lipolysis in SCAT was blunted in obese type 2 diabetics compared with age-matched lean men whereas non-diabetic obese subjects showed intermediate responses. This blunted ANP-mediated lipolytic response was accompanied by lower mRNA and protein expression of the type-A natriuretic peptide (NP) receptor and higher mRNA but reduced protein expression of the scavenging type-C receptor. Maximal ANP-induced lipolysis was lower in VAT compared with SCAT but not different between groups. Collectively, our data show that both ANP- and catecholamine-mediated lipolysis is attenuated in SCAT of obese men with type 2 diabetes, and might be partially explained by NP receptor defects. Therefore, improving maximal ANP responsiveness in adipose tissue might be a potential novel strategy to improve obesity-associated metabolic complications.

Topics: Adipocytes; Adult; Atrial Natriuretic Factor; Catecholamines; Diabetes Mellitus, Type 2; Humans; Lipolysis; Male; Middle Aged; Obesity; Subcutaneous Fat

Relative atrial natriuretic peptide (ANP) deficiency has been implicated in the pathogenesis of obesity-associated cardiovascular and metabolic disease. We tested the hypothesis that more than 5% body weight reduction through 6 months hypocaloric dieting alters ANP release at rest and more so during exercise in overweight or obese patients.. Venous mid-regional pro-ANP concentration was assessed at rest and after incremental exhaustive exercise testing before and after weight reduction. We also measured natriuretic peptide receptor A and C mRNA expression in subcutaneous adipose tissue to gauge both ANP responsiveness and clearance mechanisms.. The average weight reduction of 9.1 ± 3.8  kg was associated with reductions in visceral and subcutaneous abdominal fat mass, liver fat content, insulin resistance, and ambulatory blood pressure. However, mid-regional pro-ANP plasma concentrations were unchanged with weight loss (51 ± 24 vs. 53 ± 24  pmol/l). Exercise elicited similar acute mid-regional pro-ANP increases before and after weight loss. Adipose tissue natriuretic peptide receptor type A mRNA expression remained unchanged, whereas natriuretic peptide receptor type C mRNA decreased with weight loss.. We conclude that physical exercise acutely increases ANP release in obese patients, whereas modest diet-induced weight loss primarily affects ANP clearance mechanisms. Interventions combining weight loss and regular physical exercise may be particularly efficacious in reversing obesity-associated relative natriuretic peptide deficiency.

Topics: Adipose Tissue; Adult; Atrial Natriuretic Factor; Blood Pressure Monitoring, Ambulatory; Diet, Reducing; Exercise; Female; Humans; Insulin Resistance; Male; Middle Aged; Obesity; Receptors, Atrial Natriuretic Factor; Rest; Weight Loss; Weight Reduction Programs

Several studies have shown that obese persons have lower circulating natriuretic peptide (NP) concentrations. The cause of the relative NP deficiency seen in obese persons is poorly understood, although variation in body composition and metabolic abnormalities has been suggested to play a role. Thus, the aim of this study was to assess whether variation in circulating NP concentrations would be associated with differences in metabolic disturbances rather than with differences in body composition.. In 27 normal weight men (body mass index (BMI) = 20.0-24.9kg/m(2)) and 103 obese men (BMI ≥ 30kg/m(2)), we determined body composition (total, android, and gynoid fat mass) by dual energy x-ray absorptiometry scanning, and we measured fasting serum concentrations of midregional proatrial NP (MR-proANP) and insulin, as well as fasting plasma glucose concentrations.. Mean weight ± SD was 74.9±6.7kg in the normal weight men and 106.1±10.8kg in obese men. Applying multiple regressions, adjusting for age and weight status (normal weight vs. obese), serum MR-proANP concentrations were significantly inversely associated with serum insulin concentrations (β = -0.39; P < 0.0001) and plasma glucose concentrations (β = -0.21; P = 0.02) but not with total (β = 0.00), android (β = -0.01), or gynoid (β = 0.03) fat mass percentage (P > 0.76). No significant interaction effects between metabolic measurements or body composition measurements and weight status on MR-proANP concentrations were found (P > 0.08).. In normal weight and obese men, lower circulating NP concentrations are associated with higher insulin and glucose concentrations and not with the proportion of total fat mass or the distribution of fat mass.

Topics: Adult; Aged; Atrial Natriuretic Factor; Blood Glucose; Body Composition; Body Mass Index; Cross-Sectional Studies; Humans; Insulin; Male; Middle Aged; Obesity

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

Topics: Adult; Atrial Natriuretic Factor; Biomarkers; Body Composition; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Glucagon-Like Peptide 1; Humans; Hypoglycemic Agents; Liraglutide; Male; Middle Aged; Natriuretic Peptide, Brain; Natriuretic Peptides; Obesity; Prospective Studies

Obesity is a strong risk factor for hypertension, but the mechanisms by which obesity leads to hypertension are incompletely understood. On this background, we assessed dietary sodium intake, serum levels of natriuretic peptides (NPs), and the activity of the renin-angiotensin system in 63 obese hypertensive men (obeseHT: body mass index, ≥30.0 kg/m(2); 24-hour ambulatory blood pressure, ≥130/80 mm Hg), in 40 obese normotensive men (obeseNT: body mass index, ≥30.0 kg/m(2); 24-hour ambulatory blood pressure, <130/80 mm Hg), and in 27 lean normotensive men (leanNT: body mass index, 20.0-24.9 kg/m(2); 24-hour ambulatory blood pressure, <130/80 mm Hg). All study subjects were medication free. As a surrogate estimate for dietary sodium intake, we measured sodium excretion in a 24-hour urine collection and we measured serum levels of midregional proatrial NP and plasma levels of renin and angiotensin II. The obese men had higher mean (±SD) urinary sodium excretion (obeseHT, 213.6±85.2 mmol; obeseNT, 233.0±70.0 mmol) than the lean normotensive men (leanNT, 155.5±51.7 mmol; P=0.003). ObeseHT had lower (median [interquartile range]) serum midregional proatrial NP levels (49.2 [37.3-64.7] pmol/L) than leanNT (69.3 [54.3-82.9] pmol/L; P=0.003), whereas obeseNT had midregional proatrial NP levels in between (54.1 [43.2-64.7] pmol/L); obeseNT had lower (median [interquartile range]) plasma levels of renin (5.0 [3.0-8.0] mIU/L versus 9.0 [4.0-18.0]) and angiotensin II (2.4 [1.5-3.5] pmol/L versus 4.2 [2.2-7.9]) than obeseHT (P≤0.049), whereas obeseHT had similar plasma levels of renin and angiotensin II as leanNT (P≥0.19). Thus, despite a high sodium intake and a high blood pressure, obese hypertensive men have a relative NP deficiency and an inadequate renin-angiotensin system suppression.

Topics: Adult; Aged; Angiotensin II; Atrial Natriuretic Factor; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Body Composition; Follow-Up Studies; Humans; Hypertension; Male; Middle Aged; Obesity; Prognosis; Renin; Renin-Angiotensin System

Although many obese individuals are normoglycemic and asymptomatic of cardiometabolic complications, this apparent healthy state may be a misnomer. Since heart failure is a major cause of mortality in obesity, we investigated the effects of heme-oxygenase (HO) on heart failure and cardiometabolic complications in obese normoglycemic Zucker-fatty rats (ZFs). Treatment with the HO-inducer, hemin, reduced markers of heart failure, such as osteopontin and osteoprotegerin, abated left-ventricular (LV) hypertrophy/fibrosis, extracellular matrix/profibrotic proteins including collagen IV, fibronectin, TGF-β1, and reduced cardiac lesions. Furthermore, hemin suppressed inflammation by abating macrophage chemoattractant protein-1, macrophage-inflammatory protein-1 alpha, TNF-α, IL-6, and IL-1β but enhanced adiponectin, atrial-natriuretic peptide (ANP), HO activity, insulin sensitivity, and glucose metabolism. Correspondingly, hemin improved several hemodynamic/echocardiographic parameters including LV-diastolic wall thickness, LV-systolic wall thickness, mean-arterial pressure, arterial-systolic pressure, arterial-diastolic pressure, LV-developed pressure, +dP/dt, and cardiac output. Contrarily, the HO-inhibitor, stannous mesoporphyrin nullified the hemin effect, exacerbating inflammatory/oxidative insults and aggravated insulin resistance (HOMA-index). We conclude that perturbations in insulin signaling and cardiac function may be forerunners to overt hyperglycemia and heart failure in obesity. Importantly, hemin improves cardiac function by suppressing markers of heart failure, LV hypertrophy, cardiac lesions, extracellular matrix/profibrotic proteins, and inflammatory/oxidative mediators, while concomitantly enhancing the HO-adiponectin-ANP axis.

Topics: Adiponectin; Animals; Atrial Natriuretic Factor; Blood Glucose; Chemokine CCL2; Dinoprost; Endothelin-1; Heart Failure; Heart Function Tests; Heart Ventricles; Heme Oxygenase (Decyclizing); Hemin; Hemodynamics; Inflammation; Insulin; Insulin Resistance; Macrophage Inflammatory Proteins; Macrophages; Metalloporphyrins; Myocytes, Cardiac; Obesity; Rats; Rats, Zucker; Risk Factors; Tumor Necrosis Factor-alpha; Ultrasonography; Up-Regulation

Cardiac natriuretic peptides (NP) are major activators of human fat cell lipolysis and have recently been shown to control brown fat thermogenesis. Here, we investigated the physiological role of NP on the oxidative metabolism of human skeletal muscle. NP receptor type A (NPRA) gene expression was positively correlated to mRNA levels of PPARγ coactivator-1α (PGC1A) and several oxidative phosphorylation (OXPHOS) genes in human skeletal muscle. Further, the expression of NPRA, PGC1A, and OXPHOS genes was coordinately upregulated in response to aerobic exercise training in human skeletal muscle. In human myotubes, NP induced PGC-1α and mitochondrial OXPHOS gene expression in a cyclic GMP-dependent manner. NP treatment increased OXPHOS protein expression, fat oxidation, and maximal respiration independent of substantial changes in mitochondrial proliferation and mass. Treatment of myotubes with NP recapitulated the effect of exercise training on muscle fat oxidative capacity in vivo. Collectively, these data show that activation of NP signaling in human skeletal muscle enhances mitochondrial oxidative metabolism and fat oxidation. We propose that NP could contribute to exercise training-induced improvement in skeletal muscle fat oxidative capacity in humans.

Topics: Adaptation, Physiological; Adult; Atrial Natriuretic Factor; Cells, Cultured; Gene Expression Regulation; Genes, Mitochondrial; Heat-Shock Proteins; Humans; Lipid Metabolism; Male; Mitochondria, Muscle; Muscle Fibers, Skeletal; Muscle, Skeletal; Natriuretic Peptide, Brain; Obesity; Oxidation-Reduction; Oxidative Phosphorylation; Oxygen Consumption; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Primary Cell Culture; Receptors, Atrial Natriuretic Factor; Signal Transduction; Transcription Factors; Up-Regulation

The present study was designed to develop an animal model of hypertension and cardiac hypertrophy associated with obesity in female rats. Furthermore, we studied the involvement of the natriuretic peptide system in the mechanisms of these conditions. Obesity was induced in Wistar rats by a high fat diet and ovariectomy. The rats were divided into four groups: ovariectomized or sham-operated with high-fat diet and ovariectomized or sham-operated with control diet. After 24 weeks of diet, rats were killed, and their tissues were removed. Cardiac atrial natriuretic peptide (ANP), clearance receptor (NPr-C) gene expression was determined by PCR. ANP concentrations were measured in plasma. Ovariectomized fat-fed rats (OF) showed increased body weight, visceral fat depot and blood pressure and decreased sodium excretion compared to other groups. Also, these rats showed higher heart-to-body weight and cell diameters of ventricular cardiomyocytes and lower cardiac ANP mRNA and plasma ANP than the control group. The adipocyte and renal NPr-C mRNA of OF rats were higher than the control group. These data showed that combined ovariectomy and high fat diet elicited obesity, hypertension and cardiac hypertrophy. These results suggest that the impairment of the natriuretic peptide system may be one of the mechanisms involved not only in development of hypertension but also in cardiac hypertrophy associated with obesity in ovariectomized rats.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Cardiomegaly; Diet; Dietary Fats; Disease Models, Animal; Female; Gene Expression; Heart; Hypertension; Intra-Abdominal Fat; Obesity; Organ Size; Ovariectomy; Ovary; Rats; Rats, Wistar; Receptors, Atrial Natriuretic Factor; RNA, Messenger; Sodium

Plasma B-type natriuretic peptide (BNP) and proBNP are established markers of cardiac dysfunction. Even though obesity increases the risk of cardiovascular disease, obese individuals have reduced plasma concentrations of natriuretic peptides. The underlying mechanism is not established. We used cultured cardiomyocytes and three different mouse models to examine the impact of obesity and cardiac lipid accumulation on cardiac natriuretic peptide expression. The cardiac ventricular expression of atrial natriuretic peptide (ANP) and BNP mRNA and ANP peptide was decreased 36-72% in obese ob/ob, db/db, and fat-fed C57BL/6 mice as compared with their respective controls. The db/db and ob/ob mice displayed impaired cardiac function, whereas the fat-fed mice had almost normal cardiac function. Moreover, the ventricular expression of hypertrophic genes (α- and β-myosin heavy chain and α-actin) and natriuretic peptide receptor genes were not consistently altered by obesity across the three mouse models. In contrast, cardiac ventricular triglycerides were similarly increased by 60-115% in all three obese mouse models and incubation with oleic acid caused triglyceride accumulation and an approximately 35% (P < 0.005) depression of ANP mRNA expression in cultured HL-1 atrial myocytes. The data suggest that obesity and altered cardiac lipid metabolism are associated with reduced production of ANP and BNP in the cardiac ventricles in the setting of normal as well as impaired cardiac function.

Topics: Animals; Atrial Natriuretic Factor; Cells, Cultured; Heart Ventricles; Mice; Myocytes, Cardiac; Natriuretic Peptide, Brain; Obesity; Protein Precursors; Random Allocation; RNA, Messenger; Statistics, Nonparametric; Triglycerides

Experimental studies suggest that the natriuretic peptides influence lipid and fatty acid metabolism. Although it has been shown that obese individuals have reduced natriuretic peptide levels, conflicting data exist on the relation of natriuretic peptide levels to other metabolic risk factors.. We examined the association of plasma levels of B-type natriuretic peptide and N-terminal pro-atrial natriuretic peptide with metabolic risk factors, the metabolic syndrome, and insulin resistance in 3333 Framingham study participants free of heart failure (mean age, 58 years; 54% women). Regression analyses were performed, with adjustment for clinical and echocardiographic variables. Plasma natriuretic peptide levels were inversely associated with all components of the metabolic syndrome except for elevated blood pressure. Adjusted natriuretic peptide levels were lower in persons with the metabolic syndrome compared with those without the metabolic syndrome: In men, B-type natriuretic peptide was 24% lower (P<0.001) and N-terminal pro-atrial natriuretic peptide was 16% lower (P<0.001); in women, B-type natriuretic peptide was 29% lower (P<0.001) and N-terminal pro-atrial natriuretic peptide was 18% lower (P<0.001). Individuals with insulin resistance, as indicated by an elevated homeostasis model assessment (HOMA-IR) index, had lower levels of B-type natriuretic peptide (P=0.009 in men, P<0.001 in women) and N-terminal pro-atrial natriuretic peptide (P<0.001 in men, P=0.001 in women).. Having several metabolic risk factors is associated with low circulating natriuretic peptide levels, even after adjustment for body mass index. These findings raise the possibility that reduced natriuretic peptide activity is a manifestation of the metabolic syndrome, which may have important clinical and pathophysiological implications.

Topics: Aged; Ambulatory Care; Atrial Natriuretic Factor; Biomarkers; Body Mass Index; Female; Heart Failure; Humans; Insulin; Insulin Resistance; Male; Metabolic Syndrome; Middle Aged; Natriuretic Peptide, Brain; Obesity; Protein Precursors; Risk Factors; Ultrasonography

Abnormal neurohormonal regulation of renal sodium handling plays an important role in obesity-associated hypertension. We investigated the effect of experimental obesity on renal response to atrial natriuretic peptide (ANP).. The effect of ANP was studied in three groups of rats: (1) lean controls, (2) animals made obese by a highly palatable diet, (3) rats treated with adipose tissue hormone, leptin, for 7 days to reproduce hyperleptinemia observed in obesity.. ANP administered at a dose of 50 pmol/kg min(-1) induced about a 3-fold lower increase in Na+ and cGMP excretion in obese and leptin-treated rats than in the control group. ANP decreased Na+,K+-ATPase activity in the renal medulla only in the control group. Natriuretic effect of exogenous cGMP was also impaired in obese and leptin-treated rats. In contrast, hydrolysis-resistant cGMP derivative, 8-bromo-cGMP exerted comparable natriuretic effects in all groups. Neutral endopeptidase inhibitor, phosphoramidon, and ANP clearance receptor antagonist, C-ANP, increased urinary ANP excretion in all groups to a similar level, but their natriuretic effect was impaired in obese and leptin-treated groups. A specific inhibitor of cGMP-degrading phosphodiesterase, zaprinast, had comparable natriuretic and Na+,K+-ATPase-lowering effects in all groups and restored normal sensitivity to ANP.. (1) Dietary-induced obesity is accompanied by impaired natriuretic effect of ANP, (2) ANP resistance in obesity may be accounted for by increased leptin level, (3) accelerated degradation of cGMP may contribute to ANP resistance associated with obesity and hyperleptinemia, suggesting that inhibiting cGMP-specific phosphodiesterases may be useful in the treatment of obesity-associated hypertension.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Animals; Atrial Natriuretic Factor; Cyclic GMP; Cyclic Nucleotide Phosphodiesterases, Type 5; Drug Resistance; Hyperlipidemias; Kidney; Male; Obesity; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Rats; Rats, Wistar; Sodium

This study was designed to evaluate whether a 4-month endurance training program could improve ANP- as well as isoproterenol-mediated (beta-adrenergic receptor agonist) in situ lipolysis and adipose tissue blood flow (ATBF) in the subcutaneous adipose tissue (SCAT) of untrained overweight subjects.. Ten overweight men aged 26.0 +/- 1.4 yr with a mean body mass index of 27.6 +/- 0.2 kg.m(-2), performed aerobic exercise 5 d.wk(-1) for 4 months. Before and after the training period, SCAT responsiveness was investigated in situ during a 60-min infusion of 1 micromol.L(-1) isoproterenol and 10 micromol.L(-1) ANP through microdialysis probes. Plasma metabolic parameters and physical fitness variables were measured as well.. Endurance training significantly increased fat-free mass and VO2max, while reducing plasma insulin, glucose, NEFA, low density lipoprotein (LDL)-C and the respiratory exchange ratio at rest. Training significantly lowered resting dialysate glycerol levels in SCAT. The lipid-mobilizing effect of ANP was markedly enhanced (by 191%, P < 0.05) after training as was that of isoproterenol (by 145%, P < 0.05). Resting adipose tissue blood flow as well as ANP- and isoproterenol-mediated rise in ATBF was increased after training.. The present study shows that endurance training improves ANP- as well as beta-adrenergic-receptor-mediated lipid mobilization and ATBF in the SCAT of overweight subjects. The recovery of a higher lipolytic efficiency in adipose tissue is an important benefit of a training program in overweight subjects.

Topics: Adipose Tissue; Adrenergic beta-Agonists; Adult; Atrial Natriuretic Factor; Exercise; France; Humans; Isoproterenol; Lipid Mobilization; Male; Microdialysis; Obesity

Essential hypertension is a heterogeneous disorder that is thought to develop because of several overlapping subsets of underlying mechanisms. One such causal pathway may involve pathophysiological alterations induced by obesity. In the present study, we examined whether investigating clinically defined subtypes of hypertension, such as obesity-associated hypertension, facilitates the search for its genes. Fifty-five extended families were selected on the basis of having > or =2 siblings affected by hypertension from a geographically remote French-Canadian population. Fifteen of these families showed a high prevalence (> or =70%) of obesity. Genome-wide scan using qualitative multipoint linkage analysis (GeneHunter 2.1; marker density <10 cM) was performed in the entire set of hypertensive families and the subset with high prevalence of obesity. In the scan involving all 55 families, the most significant loci (logarithm of odds [LOD] score=2.5) were identified on chromosomes 1 (D1S1597) and 11 (D11S1999). In the scan including only the subset of families with obesity-hypertension, the most significant locus (LOD score=3.1) was found on chromosome 1 in the same region as the scan involving all families (D1S1597). Genotyping additional markers increased the significance of this locus (LOD score=3.5) and refined its position (D1S2672). Several candidate genes of obesity-hypertension are located in close proximity; these include the tumor necrosis factor receptor 2 and atrial natriuretic peptide genes. These results suggest that investigating clinically defined subtypes of hypertension, such as obesity-associated hypertension, may facilitate the search for genes of this complex disorder.

Topics: Atrial Natriuretic Factor; Chromosome Mapping; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 11; Female; France; Genetic Linkage; Genome, Human; Genotype; Humans; Hypertension; Male; Middle Aged; Obesity; Pedigree; Quebec; Receptors, Tumor Necrosis Factor, Type II

The mechanisms linking obesity to hypertension have not been established, but sodium retention and excessive sympathetic tone are key contributors. The natriuretic peptides are important regulators of sodium homeostasis and neurohormonal activation, raising the possibility that obese individuals have an impaired natriuretic peptide response.. We examined the relations of plasma B-type natriuretic peptide (BNP) and N-terminal proatrial natriuretic peptide (N-ANP) to body mass index in 3389 Framingham Study participants (1803 women) without heart failure. Multivariable regression analyses were performed, adjusting for clinical and echocardiographic covariates. BNP levels below the assay detection limit and N-ANP levels in the lowest sex-specific quartile were categorized as low. Multivariable-adjusted mean plasma BNP levels in lean (<25 kg/m2), overweight (25 to 29.9 kg/m2), and obese (> or =30 kg/m2) men were 21.4, 15.5, and 12.7 pg/mL, respectively (trend P<0.0001). Corresponding values in women were 21.1, 16.3, and 13.1 pg/mL (trend P<0.001). A similar pattern was noted for plasma N-ANP. Obese individuals had higher odds of having low plasma BNP (multivariable-adjusted odds ratios: men, 2.51; 95% CI, 1.71 to 3.68; women, 1.84; 95% CI, 1.32 to 2.58) and low plasma N-ANP (odds ratios: men, 4.81; 95% CI, 2.98 to 7.76; women, 2.85; 95% CI, 2.01 to 4.04) compared with lean individuals. Diabetes also was associated with low plasma natriuretic peptide levels, and the negative effects of obesity and diabetes on natriuretic peptide levels were additive.. Obese individuals have low circulating natriuretic peptide levels, which may contribute to their susceptibility to hypertension and hypertension-related disorders.

Topics: Atrial Natriuretic Factor; Body Constitution; Body Mass Index; Diabetes Complications; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Protein Precursors

Aim of the study was to evaluate the role of atrial (ANP) and brain natriuretic peptides (BNP) as markers of preclinical cardiac disease in obesity.. We selected 26 obese (BMI > 29 kg m(-2)) never-treated hypertensives (24-h BP > 140 and/or 90 mmHg), 26 obese normotensives (24-h BP < 130/80 mmHg) and 25 lean (BMI < or = 25 kg m(-2)) never-treated hypertensives. Each subject underwent measurements of ANP and BNP plasma levels, 24-h ambulatory blood pressure (BP) monitoring, digitized M-mode and Doppler echocardiography.. Mean values of ANP and BNP were similar among the three groups. All the subjects had normal left ventricular (LV) systolic function. Within each group ANP levels were higher in patients with LV diastolic dysfunction than in patients with normal diastolic function, and BNP levels were higher in patients with LV hypertrophy and in patients with LV diastolic dysfunction. Within each group, ANP levels were inversely correlated with LV diastolic indices, whereas BNP levels were directly correlated with LV mass index and inversely correlated with LV diastolic indices. ANP and BNP levels were not correlated with other echocardiographic parameters, age, BMI or 24-h BP values.. In normotensive and hypertensive obese subjects the relationships of ANP and BNP levels with LV morpho-functional characteristics follow the same trend as in lean hypertensives, with ANP mainly influenced by diastolic dysfunction and BNP influenced by both LV hypertrophy and LV diastolic dysfunction. Therefore ANP and BNP can be considered useful markers of preclinical cardiac disease in obesity.

Topics: Adult; Atrial Natriuretic Factor; Biomarkers; Female; Heart Diseases; Heart Ventricles; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Natriuretic Peptides; Obesity; Ventricular Dysfunction, Left; Ventricular Function, Left

Obesity is a major risk factor for the development of cardiovascular disease. Emerging evidence indicates that leptin, a protein encoded by the obesity gene, is linked with cardiac hypertrophy in obese humans and directly induces cardiomyocyte hypertrophy in vitro. However, the mechanisms by which leptin induces cardiomyocyte hypertrophy are poorly understood.. This study investigated how leptin contributes to cardiomyocyte hypertrophy. Cultured neonatal rat cardiomyocytes were used to evaluate the effects of leptin on hypertrophy. Both endothelin-1 (ET-1) and reactive oxygen species (ROS) levels were elevated in a concentration-dependent manner in cardiomyocytes treated with leptin for 4 hours compared with those cells without leptin treatment. ET-1 stimulated ROS production in a concentration-dependent manner in cardiomyocytes. The augmentation of ROS levels in cardiomyocytes treated with both leptin and ET-1 was reversed by a selective ET(A) receptor antagonist, ABT-627, and catalase, a hydrogen peroxide-decomposing enzyme. After treatment for 72 hours, leptin or ET-1 concentration-dependently increased total RNA levels, cell surface areas, and protein synthesis in cardiomyocytes, all of which were significantly inhibited by ABT-627 or catalase treatment.. These findings indicate that leptin elevates ET-1 and ROS levels, resulting in hypertrophy of cultured neonatal rat cardiac myocytes. The ET-1-ET(A)-ROS pathway may be involved in cardiomyocyte hypertrophy induced by leptin. ET(A) receptor antagonists and antioxidant therapy may provide an effective means of ameliorating cardiac dysfunction in obese humans.

Topics: Animals; Animals, Newborn; Antioxidants; Atrasentan; Atrial Natriuretic Factor; Cardiomegaly; Catalase; Cell Size; Cells, Cultured; Endothelin A Receptor Antagonists; Endothelin-1; Gene Expression Regulation; Leptin; Myocytes, Cardiac; Obesity; Oxidative Stress; Pyrrolidines; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

Topics: Antihypertensive Agents; Atrial Natriuretic Factor; Blood Volume; Cohort Studies; Cross-Sectional Studies; Diet, Reducing; Disease Susceptibility; Humans; Hypertension; Natriuretic Peptide, Brain; Obesity; Protein Precursors; Thinness

Moxonidine, an imidazoline receptor agonist that acts centrally to inhibit sympathetic activity, has been shown to reduce effectively blood pressure, fasting insulin levels, and free fatty acids. In this study, we investigated the long-term effects of moxonidine treatment on cardiac natriuretic peptides (ANP and BNP) in Spontaneously Hypertensive Obese Rats (SHROBs), a rat model that resembles human Syndrome X. SHROBs expressing spontaneous hypertension, insulin resistance, and genetic obesity (weight 590 +/- 20 g, at 30 weeks) received moxonidine in chow at 4 mg/kg/day for 15 days. Moxonidine significantly reduced not only systolic blood pressure (187 +/- 6 versus 156 +/- 5 mm Hg, P < 0.05) but also plasma ANP (1595 +/- 371 versus 793 +/- 131 pg/mL, P < 0.05) and BNP (22 +/- 3 versus 14 +/- 1 pg/mL, P < 0.04), without influencing cardiac content of either peptide. Semi-quantitative PCR revealed that atrial ANPmRNA/GAPDHmRNA decreased to 39% 6 10% of pair-fed controls, P < 0.03. In left ventricles, moxonidine also decreased ANP mRNA to 69% +/- 7% and BNP mRNA to 74% +/- 6% of control, P < 0.02, but right ventricular ANP and BNP mRNA were not affected. These findings indicate that chronic inhibition of sympathetic activity with moxonidine in SHROB is associated with decreased ventricular natriuretic peptide transcription, consistent with the cardioprotective effects of moxonidine given the role of ANP and BNP as markers of cadiac disease. Moxonidine also improves the metabolic profile in these rats, thus it may be considered the drug of choice in treatment of metabolic syndrome X.

Topics: Animals; Antihypertensive Agents; Atrial Natriuretic Factor; Blood Pressure; Female; Heart Atria; Heart Ventricles; Humans; Hypertension; Imidazoles; Male; Natriuretic Peptide, Brain; Obesity; Rats; Rats, Inbred SHR

Endurance training increases natriuretic peptide synthesis in the hypertrophied myocardium of spontaneously hypertensive rats. We examined the effects of 22-week-long treadmill exercise on plasma and tissue atrial natriuretic peptide in Zucker rats, a model of genetic obesity and moderate hypertension without clear cardiac hypertrophy. The blood pressures of the animals were measured by the tail-cuff method, and plasma and tissue samples for the peptide determinations were taken at the end of the study. The training increased heart weight to body weight ratio, while atrial natriuretic peptide contents in the right and left atrium, ventricular tissue, and plasma did not change. The exercise prevented the elevation of blood pressure, which was observed in non-exercised obese Zucker rats, and also reduced blood pressure in the lean rats. In conclusion, these results suggest that in the absence of preceding myocardial hypertrophy, the long-term exercise-induced workload is not deleterious to the heart in experimental obesity, since no changes in plasma and tissue atrial natriuretic peptide were detected.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Male; Myocardium; Obesity; Physical Conditioning, Animal; Rats; Rats, Zucker; Time Factors

The purposes of this study were to examine a new method to determine exercise intensity for obese people based on the cardiac vagal activity and to determine the effect of this approach on myocardial stress.. Forty-three middle aged obese female volunteers (age 43.7+/-6.5 y; height 1.56+/-0.05 m; body mass 66.5+/-9.3 kg; body mass index 27.3+/-2.8 kg m(2); percentage body fat 40.7+/-5.9%).. In the first experiment, 43 subjects performed a ramp exercise test on a bicycle ergometer with measurement of ECG and gas exchange parameters. In the second experiment, 11 subjects performed 45 min of constant walking exercise on a treadmill at a level corresponding to exercise intensity determined by vagal activity obtained from a ramp bicycle test. Blood pressure, endothelin 1 (ET-1), catecholamine, atrial natriuretic peptide (ANP), and brain natriuretic peptide (BNP) were measured before and after exercise.. The heart rate variability power decreased with increasing work rate, and changed little after reaching individual-specific work rate. We presumed that vagal activity disappeared at this point and that the heart rate at this exercise intensity was determined as the vagal activity threshold (T(VA)). The results showed a significant positive correlation (r=0.742, P<0.0001) between T(VA) and ventilatory threshold (VT) heart rates, although the mean heart rate of T(VA) (114.3+/-8.5 beats/min) was significantly lower (P<0.001) than that at VT (119.0+/-11.7), suggesting the cardiac vagal withdrawal occurred prior to the onset of lactate acidosis (lactic acid accumulation). Furthermore, exercise intervention experiment at T(VA) indicated that ET-1, catecholamine and BNP levels were not significantly different before and after exercise. However, ANP levels increased significantly after exercise (pre-exercise 18.6+/-5.38 vs post-exercise 44.0+/-24.87 pg/ml, P<0.001), which in turn brought about a significant post-exercise reduction in the blood pressure (SBP 117.6+/-13.7 vs 110.5+/-7.4 mmHg, P<0.05; DBP 78.6+/-6.7 vs 73.5+/-6.6 mmHg, P<0.01).. Our data suggest that it is possible to determine the exercise intensity (T(VA)) on the basis of cardiac vagal response. These results also suggest that exercise at T(VA) level is a safe exercise intensity in the light of cardiac stress, and that T(VA) may be recommended for obese people who might possess lower cardiac sympatho-vagal activity.

Topics: Adult; Atrial Natriuretic Factor; Blood Pressure; Catecholamines; Electrocardiography; Endothelin-1; Ergometry; Exercise; Exercise Test; Female; Heart Rate; Humans; Middle Aged; Natriuretic Peptide, Brain; Obesity; Oxygen Consumption; Vagus Nerve

We recently demonstrated that natriuretic peptides and especially the atrial natriuretic peptide (ANP) are powerful lipolytic agents on isolated human fat cells. To search for a possible influence of obesity on ANP responsiveness, we compared the lipolytic effects of human ANP (h-ANP) on isolated subcutaneous abdominal adipose tissue (SCAAT) fat cells from young healthy lean and obese men. The lipid-mobilizing effects of an intravenous infusion of h-ANP was studied, as well as various metabolic and cardiovascular parameters that were compared in the same subjects. h-ANP (50 ng/min/kg) was infused iv for 60 min. Microdialysis probes were inserted in SCAAT to measure modifications of the extracellular glycerol concentrations during h-ANP infusion. Spectral analysis of blood pressure and heart rate oscillations that were recorded using digital photoplethysmography were used to assess changes in autonomic nervous system activity. h-ANP induced a marked and similar increase in glycerol and nonesterified fatty acids, and a weak increase in insulin plasma levels in lean and obese men. Plasma norepinephrine concentrations rose similarly during h-ANP infusion in lean and obese men. The effects of h-ANP infusion on the autonomic nervous system were similar in both groups, with an increase in the spectral energy of the low-frequency band of systolic blood pressure variability and a decrease in the spectral energy of the high-frequency band of heart rate. In SCAAT, h-ANP infusion increased extracellular glycerol concentration and decreased blood flow similarly in both groups. The increase in extracellular glycerol observed during h-ANP infusion was not modified when 0.1 mM propranolol was added to the microdialysis probe perfusate to prevent beta-adrenoceptor activation. These data show that ANP is a potent lipolytic hormone independent of the activation of the sympathetic nervous system, and that obesity did not modify the lipid-mobilizing effect of ANP in young obese subjects.

Topics: Adipocytes; Adrenergic beta-Antagonists; Adult; Analysis of Variance; Atrial Natriuretic Factor; Biopsy, Needle; Blood Pressure; Cells, Cultured; Epinephrine; Ethanol; Fatty Acids, Nonesterified; Glycerol; Heart Rate; Humans; Isoproterenol; Male; Norepinephrine; Obesity; Propranolol; Sympathetic Nervous System; Sympathomimetics

In the obesity model of the Zucker rat, myocardial protein kinase C (PKC) activation by phorbol ester is impaired. The influence of obesity on myocardial cell signaling was investigated by studying the activation of PKC isozymes and MAP kinases (MAPK) p38 and p42/44 as well as the induction of ANP mRNA.. Isolated hearts obtained from 17-week-old lean and obese Zucker rats were perfused with 200 nM phorbol 12-myristate 13-acetate (PMA) at different time periods. Immunodetectable PKC isozymes, phosphorylated-MAPK, and ANP mRNA were determined by Western and Northern blots, respectively.. PMA promoted a marked transient translocation of ventricular PKCalpha from the cytosol to the membranes within 10 minutes in lean rats, whereas it had a much weaker effect in obese rats. Moreover, PMA induced a significant activation of PKCdelta in lean but not in obese rat hearts. After PKC activation, increases in phosphorylation levels of myocardial p38 and p42 MAPK were approximately 3-fold higher in lean rats than in obese animals. Concerning the induction of ANP, PMA transiently tripled ANP mRNA within 60 minutes in lean but not in obese rats.. In the genetically obese Zucker rat, the myocardial signal transduction cascade PKC-MAPK-ANP mRNA seems to be markedly impaired. It can be speculated that this abnormal cardiac cell signaling in obese rats reflects an early phase in the cardiac pathogenesis accompanying obesity.

Topics: Animals; Atrial Natriuretic Factor; Enzyme Activation; Female; In Vitro Techniques; Mitogen-Activated Protein Kinases; Myocardium; Obesity; Protein Kinase C; Rats; Rats, Zucker; RNA, Messenger; Signal Transduction; Tetradecanoylphorbol Acetate

We examined the effect of a hypocaloric diet on adrenomedullin (AM), atrial natriuretic peptide (ANP), and brain natriuretic peptide (BNP) in 12 obese patients with essential hypertension (age, 48-81 years; body mass index, 26-34 kg/m2). For the initial week, a standard diet of 2000 kcal/day was given, followed by 3 weeks of a hypocaloric diet of 850 kcal/day, with a constant intake of sodium. The patients lost 3.7 +/- 0.2 kg body weight during the hypocaloric diet period (p < 0.0001). The decrease in blood pressure during the study period was 10.3 +/- 3.6 mmHg systole (p = 0.017) and 4.2 +/- 3.2 mmHg diastole (NS). Plasma AM concentration was decreased significantly from 4.88 +/- 0.46 to 3.97 +/- 0.38 pmol/l by the hypocaloric diet (p = 0.004). Plasma ANP and BNP concentrations were also decreased significantly by the hypocaloric diet (p = 0.042 for each). These results demonstrate, for the first time, that plasma AM concentration as well as plasma ANP and BNP concentrations are decreased by a hypocaloric diet in obese patients with essential hypertension. These vasodilator peptides may act against further elevation in blood pressure in obese patients with essential hypertension.

Topics: Adrenomedullin; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Energy Intake; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Peptides

The expression of the natriuretic peptide clearance receptor is abundant in human and rat adipose tissue, where it is specifically inhibited by fasting. In obese hypertensives, plasma atrial natriuretic peptide (ANP) levels were found to be lower than in obese normotensives. Therefore, the increased adipose mass might influence ANP levels and/or its biological activity. The aim of the present study was to evaluate whether the humoral, hemodynamic, and renal effects of exogenous ANP in obese hypertensives might be enhanced by a very low calorie diet. Eight obese hypertensives received a bolus injection of ANP (0.6 mg/kg) after 2 weeks of a normal calorie/normal sodium diet, and blood pressure (BP), heart rate, ANP, cGMP, plasma renin activity, and aldosterone were evaluated for 2 hours before and after the injection. Diuresis and natriuresis were measured every 30 minutes. The patients then started a low calorie/normal sodium diet (510 kcal/150 mmol/d) for 4 days, and then the ANP injection protocol was repeated. The low calorie diet induced a slight weight loss (from 90.6+/-1.1 to 87. 7+/-1.2 kg; P<0.01), which was accompanied by increase of cGMP excretion (from 146.0+/-10.1 to 154.5+/-9.5 nmol/24 h; P<0.05) together with a reduction of BP (P<0.01 versus basal levels). ANP injection after diet was followed by an increase of ANP levels similar to that observed before diet, but plasma cGMP, diuresis, and natriuresis increased significantly only after diet. Similarly, the decrease of BP after ANP administration was significantly higher after diet (change in mean arterial pressure, -6.4+/-0.7 versus -4. 0+/-0.6 mm Hg; P<0.05) as well as that of aldosterone (P<0.01). These data show that a low calorie diet enhances the humoral, renal, and hemodynamic effects of ANP in obese hypertensives and confirm the importance of caloric intake in modulating the biological activity of ANP, suggesting that the natriuretic peptide system can play a role in the acute changes of natriuresis and diuresis associated with caloric restriction.

Topics: Aldosterone; Animals; Atrial Natriuretic Factor; Diet; Diuresis; Female; Hemodynamics; Humans; Hypertension; Male; Middle Aged; Obesity; Rats; Renin

The clearance receptor for natriuretic peptides (NPRC), a candidate gene for essential hypertension, is highly expressed in adipose tissue, where is nutritionally regulated. The objectives of the present study were to sequence the human 5'-flanking regulatory region of NPRC, to identify allelic variants and their frequencies, and to study the genotype/phenotype correlation in hypertensive patients.. Using polymerase chain reaction (PCR) and direct automated sequencing, a biallelic (A/C) polymorphism was detected at position -55 in a conserved promoter element named P1. The novel C(-55) variant makes the promoter sequence identical to the mouse gene and introduces a second Hgal site in the amplified DNA, allowing the genotyping of a large number of subjects. In a random sample of 232 white Caucasians the C(-55) allele was more commonly found (81.7% of all alleles) with 155 CC (66.8%), 69 AC (29.7%) and only eight AA (3.5%) genotypes. Atrial natriuretic peptide (ANP) levels were determined in 84 patients with essential hypertension. In the presence of obesity (body mass index (BMI) > or = 30 kg/m2) the homozygous CC hypertensives (n = 21) had significantly lower plasma ANP (33.6 +/- 11.1 pg/ml) compared with the AC patients (n = 11; 46.8 +/- 15.9 pg/ml; P = 0.01), whereas systolic blood pressure (SBP) and mean blood pressure (MBP) had the opposite association (SBP 163.9 +/- 18.7 versus 150.9 +/- 12.9 and MBP 123.3 +/- 12 versus 114.5 +/- 5.9 mmHg; P< 0.05). The difference in ANP levels were also present when overweight patients (BMI > or = 27 kg/m2) were considered.. A common 'ancestral' C(-55) variant of the NPRC P1 promoter is associated with lower ANP levels and higher SBP and MBP in obese hypertensives. The C(-55) variant, in the presence of increased adiposity, might reduce plasma ANP through increased NPRC-mediated ANP clearance, contributing to higher blood pressure.

Topics: Adult; Aged; Alleles; Animals; Atrial Natriuretic Factor; Blood Pressure; Body Mass Index; Female; Gene Frequency; Genetic Testing; Genotype; Guanylate Cyclase; Humans; Hypertension; Male; Mice; Middle Aged; Molecular Sequence Data; Obesity; Polymerase Chain Reaction; Polymorphism, Genetic; Promoter Regions, Genetic; Receptors, Atrial Natriuretic Factor; Regulatory Sequences, Nucleic Acid; Sequence Homology, Nucleic Acid

Topics: Atrial Natriuretic Factor; Diet, Reducing; Humans; Hypertension; Obesity

To study the regulation of antidiuretic hormone (ADH) and atrial natriuretic peptide (ANP) in obese and lean women with a swelling syndrome.. Thirty-four obese women and 12 lean women with a swelling syndrome and an abnormal isotopic test of capillary permeability to albumin were investigated.. After 10 nocturnal hours of fluid restriction, subjects were asked at 8am to ingest a tap water load of 20 ml/kg within 10 min and to remain strictly recumbent until twelve noon on the first day, and to remain standing and to walk around until twelve noon on the second day. Free water clearance and the cGMP/creatinine and albumin/creatinine ratios were determined hourly in the morning.. The total 4 h-urinary volume/ingested water volume ratio was significantly lower on the second day both in the lean and the obese patients, the differences being slightly larger in the obese patients. The increase in free water clearance was significantly less on the second day in the obese patients. The increase in cGMP/creatinine ratio was also significantly lower on the second day in the obese patients. The maximum level of the urinary albumin/creatinine ratio was significantly higher on the second day in the obese patients.. In obese women with a swelling syndrome: (1) The higher increase in the urinary albumin excretion rate after water loading followed by a sustained upright position suggests a widespread alteration in capillary function, which is also indicated by the isotopic test of capillary permeability to albumin. (2) The water load-induced inhibition of ADH secretion and stimulation of ANP secretion or ANP activity, more defective in the upright position than in the recumbent one, is probably another major contributing factor to orthostatic oedema.

Topics: Adult; Albumins; Atrial Natriuretic Factor; Capillary Permeability; Case-Control Studies; Creatinine; Drinking; Edema; Female; Guanosine Monophosphate; Humans; Middle Aged; Obesity; Posture; Statistics, Nonparametric; Vasopressins

Based on our studies at the Hypertension research unit, we have found that the renin-angiotensin aldosterone. System (RAAS) undergoes several changes being the following the most relevant: Low plasma renin concentration (LPRC), while the plasma Aldosterone concentration is high (HPAC). At the same time we found calcium metabolism alterations: High urine calcium excretion, low serum ionic calcium and high PTH level. This alterations are more evident if the elder patient become hypertensive. We have found this changes in several groups in our community: black, ancient, obese and diabetic patients; who more often suffer hypertension and they must be followed up closely. In this group there are the sodium dependent hypertensive and they are the one who can get beneficial effects from the low salt diet and high calcium intake. When we studied the low plasma renin hypertensive we found the calcium changes mentioned before in ancient patient, as well as, high urine Zinc excretion. When we gave and oral calcium supplement to these patients, we saw that the calcium and Zinc alterations mentioned before were corrected. The high plasma renin concentration hypertensive patients showed low serum magnesium concentration and high urine magnesium excretion. A brief comment on the possible role of oxidative stress on essential hypertension is made.

Topics: Adult; Aged; Aldosterone; Antihypertensive Agents; Atrial Natriuretic Factor; Black People; Calcium; Comorbidity; Diabetes Mellitus; Disease Susceptibility; Endothelium, Vascular; Female; Humans; Hypertension; Lipoxygenase; Magnesium; Male; Middle Aged; Models, Biological; Obesity; Oxidative Stress; Parathyroid Hormone; Renin-Angiotensin System; Risk Factors; Sodium, Dietary; Venezuela; Zinc

Human and rat adipose tissue contain very high levels of natriuretic peptides clearance receptor messenger (m)RNA, and fasting inhibits its gene expression in adipose tissue. In this study we evaluated plasma atrial natriuretic peptide (ANP) and gene expression of biologically active type A natriuretic peptide receptor (NPr-A) and clearance natriuretic peptide receptor (NPr-C) in adipose tissue of obese hypertensive and obese normotensive patients.. We studied 27 untreated obese hypertensives, 26 obese normotensives (body mass index > or = 30 kg/m2), 24 non-obese essential hypertensives and 23 lean healthy subjects (body mass index < or = 25 kg/m2). Blood samples were withdrawn for ANP, plasma renin activity and aldosterone radioimmunoassays. Subcutaneous peri-umbilical adipose tissue samples were obtained, by needle aspiration, in 13 obese hypertensives and in 12 obese normotensives and used for RNA extraction. Then, complementary synthesis and semiquantitative polymerase chain reaction (PCR) with primers complementary to sequences of different exons of the genes encoding for NPr-A, NPr-C and beta-actin, were performed. 32P-labeled PCR products were separated by electrophoresis, blotted onto nylon membranes, and the exposed autoradiographic films were analysed by densitometry. NPr signals were normalized by the beta-actin expression level.. Plasma ANP was lower in obese hypertensives than in obese normotensives (37.5+/-7 versus 43.2+/-6 pg/ml, P< 0.05), but was higher in non-obese hypertensives than in non-obese normotensives. In contrast, plasma renin activity and aldosterone were higher in the obese hypertensives. Although NPr-A and NPr-C expression were not statistically different between the two obese groups, the NPr-A: NPr-C mRNA ratios were significantly lower in obese hypertensives (P < 0.03).. Our data suggest that in obese hypertensives compared to obese normotensives, the lower NPr-A: NPr-C ratio might determine decreased biological activity and/or an increased clearance of natriuretic peptide in adipose tissue, suggesting that the natriuretic peptide and its receptor system may be important in obesity-related hypertension where ANP levels are lower.

Topics: Actins; Adipose Tissue; Aldosterone; Atrial Natriuretic Factor; Biopsy, Needle; DNA Primers; Female; Gene Expression; Guanylate Cyclase; Humans; Hypertension; Male; Middle Aged; Obesity; Polymerase Chain Reaction; Receptors, Atrial Natriuretic Factor; Renin; RNA, Messenger

Hypertension is commonly associated with diabetes mellitus. The aim of the present study was to explore the pathophysiological significance of the natriuretic peptide (NP) system in hypertension associated with genetically obese/hyperglycemic Wistar fatty rats. The messenger RNA (mRNA) levels of the two biologically active NP receptors, NP-A receptor [more specific for atrial natriuretic peptide (ANP)] and NP-B receptor [more specific for C-type natriuretic peptide (CNP)], and CNP mRNA levels were determined in the aorta and kidney by ribonuclease protection assay. Plasma ANP levels were determined by RIA. Both NP-A and NP-B receptor mRNA levels in the aortae of Wistar fatty rats were double those in Wistar lean rats. Plasma ANP levels and CNP mRNA levels in the aorta of Wistar fatty rats were also significantly higher than those in Wistar lean rats. In contrast, there was no significant difference in renal levels of the mRNA for both NP receptors and CNP between the two strains. Administration of a NP-A and -B receptor antagonist, HS-142-1, to Wistar fatty rats resulted in a significant increase in systolic blood pressure and a larger decrease in plasma cGMP level than that in Wistar lean rats, with no difference in the extents of decrease in urine volume and urinary sodium excretion between the two strains. These results suggest that both the ANP/NP-A system and the CNP/NP-B system in vessels are up-regulated at the level of gene expression and may, thus, play an important role in counteracting the hypertension associated with diabetes mellitus.

Topics: Animals; Aorta; Atrial Natriuretic Factor; Blood Vessels; Cyclic GMP; Diuresis; Guanylate Cyclase; Hyperglycemia; Hypertension; Kidney; Male; Natriuresis; Natriuretic Peptide, C-Type; Obesity; Polysaccharides; Proteins; Rats; Rats, Wistar; Receptors, Atrial Natriuretic Factor; RNA, Messenger

Topics: Adult; Atrial Natriuretic Factor; beta-Endorphin; Blood Glucose; Female; Humans; Insulin; Male; Middle Aged; Naloxone; Obesity

Plasma atrial natriuretic peptide (ANP) concentrations were determined in basal conditions and after infusion of 1000 ml of 0.9% NaCl in women with anorexia nervosa, in normotensive obese women and in healthy women of the control group. Additionally, in the obese women and in the controls, plasma ANP was measured after iv injection of clonidine. Anorectic patients were investigated in the period of weight loss (mean deficit of body weight was 40%). The mean body mass index (BMI) in the obese women was 36.44 +/- 0.36 kg/m2. Basal plasma ANP concentrations were significantly higher in both anorectic and obese women (p < 0.001 and p < 0.01, respectively). The response of ANP to acute water load was markedly blunted in anorexia nervosa and in obesity (delta % = 232% in control group, 14% in anorexia nervosa and 21% in obesity. A significant increase of ANP was found after iv injection of clonidine in the control group and in obesity (p < 0.001 and p < 0.01, respectively). However, the increase of response (expressed as a percentage change) in obese patients was lower than that in the control group (delta % = 64% and 199%, respectively). The response of ANP to alpha 2-adrenergic stimulation was higher than to hemodynamic stimulus. Our results suggest that the disturbed control of neuropeptides and neurotransmitters as well as changes in peripheral metabolism may explain the impaired responsibility of ANP to hemodynamic stimuli in anorectic and obese patients.

Topics: Adolescent; Adult; Anorexia Nervosa; Atrial Natriuretic Factor; Body Weight; Clonidine; Female; Humans; Injections, Intravenous; Middle Aged; Obesity; Sodium Chloride; Water

It is well-known that the prevalence of hypertension progressively increases with body weight. Since the major physiological activities of atrial natriuretic factor (ANF) are its natriuretic, diuretic and vasodilatory effects, the aim of the present study was to investigate the ANF basal plasma levels and platelet receptor number in 15 young normotensive obese (O) and 12 age-matched normal weight healthy (C) women. ANF effectiveness was also studied in eight of the obese and seven of the control women, after an intravenous bolus of the hormone (human ANF (99-126): 0.5 mg/kg body weight). Results are expressed as means+s.d. Basal ANF plasma levels were similar between obese (18.2 +/- 9.7 pg/ml) and control women (12.3 +/- 7.7 pg/ml), whereas obese patients showed an increase density of platelet ANF-binding sites (clearance receptors) (C: 28.7 +/- 33.5 fmol/10(9) cells; O: 39.6 +/- 4.6 fmol/10(9) cells; P < 0.001), without apparent differences in receptor affinity (Kd) (C: 6.0 +/- 3.0 pM; O: 7.0 +/- 2.0 pM). The biological response to ANF, evaluated by changes of mean blood pressure levels (C: 5 +/- 1 mmHg; O: 1 +/- 1 mmHg; P < 0.001) and the percentage increase of diuresis (C: 159 +/- 52%; O: 81 +/- 62%; P < 0.01) and natriuresis (C: 205 +/- 129%; O: 99 +/- 41%; P < 0.05) was significantly reduced in obese patients. The percentage increase in sodium excretion was inversely related to the basal insulin concentrations in the obese group (r = 0.64, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Atrial Natriuretic Factor; Blood Platelets; Blood Pressure; Diuresis; Female; Humans; Natriuresis; Obesity; Premenopause; Receptors, Atrial Natriuretic Factor

To investigate whether the response of salt-regulating hormones to volume expansion is impaired in obese subjects, we assessed the effects of saline load (0.25 mL/kg.min.120 min) in 9 young, healthy, normotensive obese subjects (body mass index, > 30 kg/m2) and in 10 lean control subjects (body mass index, < 25 kg/m2) matched for age, gender, height, and mean blood pressure. Hematocrit, plasma renin activity (PRA), plasma aldosterone (PA), atrial natriuretic factor (ANF), and urinary sodium excretion (UNaV) were evaluated. Saline load increased ANF levels significantly (P < .001) in lean subjects at both 60 and 120 minutes, whereas they decreased in obese subjects. Such decreases became significant (P < .01) at 120 minutes. Suppression of PRA and PA by saline load were more marked in lean than obese subjects. Hematocrit decreased in both groups, and UNaV increased more in lean than obese subjects during saline load. Comparisons of percent changes in ANF, PRA, and PA after saline load showed that the responses of lean and obese subjects were significantly different (P < .001 for ANF at both 60 and 120 minutes; P < .05 for PRA and PA at both 60 and 120 minutes). In conclusion, the lack of ANF response and the reduced suppression of PRA and PA to saline load indicate a dysfunction of these systems in obese subjects. This alteration may be involved in the higher susceptibility of obese subjects to developing hypertension.

Topics: Adult; Aldosterone; Atrial Natriuretic Factor; Blood Glucose; Blood Pressure; Body Mass Index; Creatinine; Diastole; Echocardiography; Female; Heart Rate; Hematocrit; Humans; Insulin; Male; Obesity; Reference Values; Renin; Sodium; Systole

Aim of this study was to verify the existence of a correlation between the insular hormones and the atrial natriuretic factor (ANF). We studied 70 subjects (20 control, 20 obese, 20 non insulin-dependent diabetic obese, 10 insulin-dependent diabetic subjects) submitted to a glucagon test (1 mg i.v.). Blood samples were collected at -15, 0, 3, 6, 12, 15, 30, 60, 120, 150 minutes to assay insulin, C-peptide, serum electrolytes and ANF levels. The results to point out are: the ANF basal values are significantly higher (p < 0.01) in non insulin-dependent obese patients than in controls; the obese subjects also present a significant difference (p < 0.05). After glucagon injection no variations have been found in the ANF values until the 15th minute; then the controls, the obese and, above all, the non insulin-dependent diabetic obese subjects showed a significant increase of the ANF values between 60' and 90' (basal values 38 +/- 4 ng/ml; 90' values 85 +/- 7 ng ml). As these high values appear only after the induction of hyperinsulinism in our experiment and are not present in the type-1 diabetic subjects, it's probable that insulin, rather than glucagon, stimulates, directly or indirectly, the ANF secretion. If this hypothesis is confirmed, the correlation between insulin and ANF should deserve attention from a therapeutic point of view in subjects with glycometabolic imbalance.

Topics: Adolescent; Adult; Atrial Natriuretic Factor; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glucagon; Humans; Hyperinsulinism; Insulin; Male; Middle Aged; Obesity; Potassium; Secretory Rate; Sodium

To examine the relation between plasma atrial natriuretic peptide (ANP) and the natriuresis of fasting.. ANP, aldosterone and renin were examined during natriuresis of fasting in 25 obese essential hypertensive patients and nine overweight normotensive subjects placed on a supervised 500-KCal diet composed of 50% carbohydrates, 30% fat and 20% protein, and unlimited salt. Twenty-four-hour urinary electrolytes were measured on days 0, 4, 7 and 10 of the diet.. Urinary sodium concentration nearly doubled in the patients on day 4, and increased 1.4-fold in the normotensive controls. Plasma ANP rose nearly threefold in the hypertensives on day 4 and nearly doubled in the normotensives. Patients and controls showed similar patterns of natriuresis and ANP secretion during the diet.. We conclude that there is a clear association between ANP levels and natriuresis of fasting.

Topics: Adolescent; Adult; Aged; Aldosterone; Atrial Natriuretic Factor; Fasting; Female; Humans; Hypertension; Male; Middle Aged; Natriuresis; Obesity; Sodium

The pathophysiological mechanisms in hypertension may differ in men and women. Plasma renin activity was measured in 27 premenopausal, never-treated hypertensive women (blood pressure 141 +/- 2/93 +/- 1 mm Hg) and in 18 age-matched normotensive women (blood pressure 113 +/- 2/71 +/- 2 mm Hg). All subjects were unaware of their blood pressure status. The hypertensive women had on average lower plasma renin activity (0.21 +/- 0.03 nmol/L/h) than their normotensive controls (0.42 +/- 0.07 nmol/L/h, P less than .01). Serum estradiol was also lower in the hypertensive women (0.57 +/- 0.06 v 0.81 +/- 0.09 nmol/L, P less than .05). No difference in epinephrine, norepinephrine, atrial natriuretic peptide, or vasopressin was found between the groups. Plasma renin activity was positively correlated to plasma norepinephrine in the hypertensive women only (r = 0.41, P less than .05). Since low renin hypertension is associated with less cardiovascular complications, this may offer an explanation for the better prognosis of hypertension in women.

Topics: Adult; Aging; Arginine Vasopressin; Atrial Natriuretic Factor; Blood Pressure; Calcium; Catecholamines; Estradiol; Female; Humans; Hypertension; Menopause; Norepinephrine; Obesity; Potassium; Progesterone; Renin; Sodium; Sympathetic Nervous System

The N-terminus of the atrial natriuretic factor (ANF) prohormone (ie, proANF 1-98) contains two vasodilatory peptides consisting of amino acids (aa): aa 1-30 (ie, proANF 1-30) and aa 31-67 (ie, proANF 31-67) of the 126 aa prohormone. The relationship of this N-terminus to the renin-aldosterone axis and blood pressure reduction was investigated in 18 obese subjects (5 hypertensive and 13 normotensive) placed on a 12-week, low sodium (40 mmol), weight reducing diet. The N-terminus of the ANF prohormone and proANF 31-67, which circulates as a distinct entity after being proteolytically cleaved from the N-terminus, were significantly (p less than 0.001) higher (767 +/- 1.01 and 816 +/- 135 fmol/ml) in the obese hypertensive group compared with the obese normotensive group (377 +/- 24 and 356 +/- 17 fmol/ml, respectively) prior to beginning the weight reduction program. There was a dramatic fall in the N-terminus and in proANF 31-67 after 1 week of weight reduction in both obese groups, which correlated with the decrease in mean arterial pressure during the first week and throughout the 12 weeks of weight reduction (r = .54, p less than 0.001 and r = .59, p less than 0.001, respectively). ProANF 1-98 had a significant (p less than 0.01) inverse correlation with plasma renin in both obese groups. ProANF 31-67, likewise, had an inverse correlation with plasma renin in the hypertensive (p less than 0.002), as well as the normotensive (p less than 0.03) subjects. ProANF 31-67 did not significantly correlate with aldosterone in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aldosterone; Atrial Natriuretic Factor; Blood Pressure; Diet, Reducing; Female; Humans; Hypertension; Male; Middle Aged; Obesity; Peptide Fragments; Protein Precursors; Time Factors; Weight Loss

Topics: Atrial Natriuretic Factor; Humans; Hypertension; Obesity; Weight Loss

The purpose of this study was to determine if the reflex response to a saline load is altered in the obese Zucker rat. The obese Zucker rat is a genetic model of obesity and insulin-resistant diabetes that has been reported to have high blood pressure. We examined the reflux renal responses to volume expansion in both anesthetized obese and lean Zucker rats. Initial blood pressure was significantly elevated in the obese Zucker rats compared with the lean controls. Urine flow and sodium excretion from innervated and denervated kidneys were measured before and after volume expansion with normal saline. Volume expansion resulted in significantly less urine flow and sodium excretion in the obese than the lean Zucker rats. This response was evident in both the intact and denervated kidneys. Rats were then infused with atrial natriuretic peptide (ANP) to determine if natriuretic and diuretic responses were altered in these rats. The diuretic action of ANP was not significantly reduced in the obese Zucker rat. However, the natriuretic action of ANP was significantly attenuated in the obese rats. These results indicate that the reflux response to an acute saline load is attenuated in the obese Zucker rat and that this decreased response may be due to a reduction in the direct action of ANP on the kidney.

Topics: Animals; Atrial Natriuretic Factor; Blood Glucose; Blood Pressure; Body Weight; Denervation; Glomerular Filtration Rate; Heart Rate; Insulin; Kidney; Obesity; Organ Size; Rats; Rats, Zucker; Reference Values; Renal Circulation; Sodium; Sodium Chloride

Renal clearance studies were conducted in conscious, chronically catheterized obese and lean Zucker rats to investigate the natriuretic responses to i) acute IV infusion of isotonic NaCl = 5% of total body weight and ii) IV infusion of alpha rat atrial natriuretic peptide (ANP) in a dose of 300 ng/kg/min. In the baseline state, arterial blood pressure (BP) was significantly higher in obese vs lean rats. Absolute values of GFR and sodium excretion were similar but lower in obese vs lean rats when factored for body weight. In the 2 h period during and after NaCl infusion, obese rats showed a greater natriuresis vs lean while BP rose significantly and similarly. ANP infusion was natriuretic in obese rats but had no effect on lean rats. ANP lowered BP in both groups but BP remained higher in obese vs lean rats at all times. These studies show that in the chronic, unstressed preparation the 6-8 month old, female Zucker obese rat has a higher BP vs the 6-8 month old lean Zucker. The short term natriuretic response to either a NaCl load or ANP infusion is greater in obese vs lean Zuckers and the depressor response to ANP is intact in obese Zuckers. Thus the higher BP in this model of obesity is unlikely to be due to either a defective response to ANP or to a defect in the renal response to acute sodium challenge.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Female; Glomerular Filtration Rate; Hypertension; Isotonic Solutions; Natriuresis; Obesity; Rats; Rats, Zucker; Sodium Chloride

Obesity is usually associated with expansion of blood volume. Therefore, we studied whether obesity affects cardiac and plasma atrial natriuretic peptide (ANP) levels in experimental animal model. Mice made obese with gold thioglucose developed cardiac hypertrophy associated with increases in ANP in atrial tissue and plasma. There were significant (p less than 0.01) correlations between the cardiac ANP concentration and body weight or cardiac weight. These data suggest that enhanced synthesis of atrial ANP in obese mice can be mainly ascribed to increased blood volume associated with cardiac hypertrophy.

Topics: Animals; Atrial Natriuretic Factor; Aurothioglucose; Body Weight; Heart; Male; Mice; Mice, Obese; Myocardium; Obesity; Organ Size; Radioimmunoassay; Ventromedial Hypothalamic Nucleus

The effect of obesity and weight reduction upon circulating concentrations of atrial natriuretic peptide was assessed in an experimental model of the disease. Obese rats weighing in excess of 750 g were compared with formerly obese animals subjected to a 15-week period of caloric restriction resulting in a 40% reduction in body weight. Mean adipocyte size was significantly reduced with weight loss, as was estimated body fat. Mean arterial blood pressure remained normotensive for both groups, but a significant reduction in heart rate was associated with weight reduction. Circulating atrial natriuretic peptide was significantly elevated in the lean rats, which also exhibited decreased plasma renin activity and a negative sodium balance. Analysis of heart to body weight ratios implied that an obesity-associated, volume-induced cardiac hypertrophy remained even after the normalization of body fat. These results suggest that the diuresis and natriuresis accompanying weight reduction may be facilitated by atrial natriuretic peptide, which was elevated in part due to a persistent left ventricular hypertrophy following the transition from the obese to lean condition.

Topics: Adipose Tissue; Animals; Atrial Natriuretic Factor; Heart; Hemodynamics; Kidney; Obesity; Rats; Weight Loss

The relationship between atrial natriuretic factor (ANF), the renin-aldosterone axis, and blood pressure reduction with weight loss was investigated in 18 obese subjects (five hypertensive and 13 normotensive) placed on a 12-week, low-sodium (40 mmol), weight-reducing diet. ANF was significantly higher (P less than .02) in the obese hypertensive group compared with the obese normotensive group throughout the study. There was a dramatic fall in the circulating concentration of ANF after 1 week of weight reduction in both obese groups. Mean arterial pressure fell significantly in both groups, with the hypertensive group becoming normotensive during the first week of the diet. The marked changes in ANF and mean arterial pressure during the first week of the diet appeared related to reduced salt intake. Mean arterial pressure and ANF concentrations, however, continued to fall during the eighth to 12th week of weight reduction diet in the hypertensive patients when salt intake had been unchanged for several months. In both the hypertensive and normotensive subjects ANF paralleled blood pressure changes (r = .54, P less than .0001) throughout the 12-week study period. ANF was inversely correlated with plasma renin activity and aldosterone, with the most dramatic changes in their concentrations being during the first week of the diet. These results demonstrate that weight loss while ingesting a controlled low sodium diet is accompanied by changes in ANF that directly correlate with changes in blood pressure and inversely correlate with changes in the renin-aldosterone axis, which ANF is known to inhibit.

Topics: Adult; Aged; Aldosterone; Atrial Natriuretic Factor; Blood Pressure; Electrolytes; Female; Heart Rate; Humans; Hypertension; Male; Middle Aged; Obesity; Renin; Weight Loss