atrial-natriuretic-factor and Metabolic-Syndrome

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

Natriuretic peptides are a group of hormones including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C type (CNP), urodilatin and guanilyn. ANP (half-life: 2-4 min), is secreted by the atrium, BNP (half-life: 20 min) by the ventricle, CNP by the vascular endothelium, urodilatin by the kidney and guanylin by the intestine. These natriuretic peptides prevent water and salt retention through renal action, vasodilatation and hormonal inhibition of aldosterone, vasopressin and cortisol. These peptides also have a recently demonstrated metabolic effect through an increase of lipolysis, thermogenesis, beta cell proliferation and muscular sensitivity to insulin. Blood levels of these natriuretic peptides depend on "active NPR-A receptors/clearance NPR-C receptors", the last ones being abundant on adipocytes. Therefore, natriuretic peptides act as adipose tissue regulator and constitute a link between blood pressure and metabolic syndrome. They are used as markers and treatment of cardiac failure. Other applications are on going. BNP and NT-proBNP (inactive portion de la pro-hormone) are used as markers of cardiac failure since they have a longer half-life than ANP. BNP decrease is quicker and more important than that one of NT-ProBNP in case of improvement of cardiac failure. Chronic renal insufficiency and beta-blockers increase BNP levels. BNP measurement is useless under treatment with neprilysine inhibitors such as sacubitril, one of the neutral endopeptidases involved in catabolism of natriuretic peptides. The association sacubitril/valsartan is a new treatment of chronic cardiac failure, acting through the decrease of ANP catabolism.

Topics: Atrial Natriuretic Factor; Blood Pressure; Endocrine System; Energy Metabolism; Hemodynamics; Humans; Metabolic Syndrome; Natriuretic Agents; Receptors, Atrial Natriuretic Factor; Risk Factors

Blood pressure is maintained for preventing from the progression of damage of central nervous system. Endocrine system plays important roles in the prevention from the damage through the functional deviation. Hypertension is one of the results of the endocrinological deviation. Although the hypertension induced by the endocrinological deviation is a risk for the progression of metabolic syndrome, it is important in the maintaining activity of central nervous system.

Topics: Aged; Aging; Arteriosclerosis; Atrial Natriuretic Factor; Blood Volume; Cardiac Output; Central Nervous System; Endocrine System; Glucocorticoids; Growth Substances; Humans; Hypertension; Metabolic Syndrome; Parathyroid Hormone; PPAR gamma; Renin-Angiotensin System; Risk; Vascular Resistance; Vasopressins

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

Metabolic syndrome (MetS) is a cluster of factors that increase the risk of developing diabetes, stroke, and heart failure. The pathophysiology of injury by ischemia/reperfusion (I/R) is highly complex and the inflammatory condition plays an important role by increasing matrix remodeling and cardiac apoptosis. Natriuretic peptides (NPs) are cardiac hormones with numerous beneficial effects mainly mediated by a cell surface receptor named atrial natriuretic peptide receptor (ANPr). Although NPs are powerful clinical markers of cardiac failure, their role in I/R is still controversial. Peroxisome proliferator-activated receptor α agonists exert cardiovascular therapeutic actions; however, their effect on the NPs' signaling pathway has not been extensively studied. Our study provides important insight into the regulation of both ANP and ANPr in the hearts of MetS rats and their association with the inflammatory conditions caused by damage from I/R. Moreover, we show that pre-treatment with clofibrate was able to decrease the inflammatory response that, in turn, decreases myocardial fibrosis, the expression of metalloprotease 2 and apoptosis. Treatment with clofibrate is also associated with a decrease in ANP and ANPr expression.

Topics: Animals; Arrhythmias, Cardiac; Atrial Natriuretic Factor; Clofibrate; Inflammation; Ischemia; Metabolic Syndrome; Natriuretic Peptides; PPAR alpha; Rats; Receptors, Atrial Natriuretic Factor; Reperfusion Injury

The action of atrial natriuretic peptide (ANP) on natriuresis, diuresis and vasodilatation, insulin resistance, liver, kidney, and adipose tissue may contribute to the healthy metabolic and cardiovascular development. Even though the circulating level of ANP is reduced in patients with obesity, its response to weight loss remains poorly explored in pediatric populations.. To evaluate the effects of ANP variations in response to interdisciplinary weight loss intervention on metabolic syndrome (MetS) and cardiometabolic risks in adolescents with obesity.. 73 adolescents with obesity attended a 20-week clinical interdisciplinary weight loss therapy including clinical, nutritional, psychological and exercise training approach. Body composition, biochemical analyses and blood pressure were evaluated. MetS was classified according to the International Diabetes Federation (IDF) (2007). After the treatment, volunteers were divided according to Increasing (n=31) or Decreasing (n=19) ANP plasma levels.. Both groups present significant reduction of body weight, Body Mass Index (BMI), waist, neck and hip circumferences (WC, NC and HC, respectively) and increasing fat-free mass (FFM). Interestingly, a significant reduction in body fat, TG/HDL-c ratio and MetS prevalence (from 23% to 6%) was observed in the Increased ANP group only.. This study suggests that an increase in ANP serum levels after weight loss therapy could be associated with improvements in cardiometabolic risks and the reduced prevalence of MetS in adolescents with obesity.. A ação do peptídeo natriurético atrial (ANP) na natriurese, diurese e vasodilatação, resistência à insulina, fígado, rim e tecido adiposo pode contribuir para o desenvolvimento metabólico e cardiovascular saudável. Embora o nível circulante de ANP seja reduzido em pacientes com obesidade, sua resposta à perda de peso ainda é pouco explorada em populações pediátricas.. Avaliar os efeitos das variações do ANP em resposta à intervenção interdisciplinar para perda de peso na Síndrome Metabólica (SMet) e nos riscos cardiometabólicos em adolescentes com obesidade.. 73 adolescentes com obesidade participaram de uma terapia interdisciplinar para perda de peso de 20 semanas, incluindo uma abordagem clínica, nutricional, psicológica e de exercícios físicos. A composição corporal, análises bioquímicas e pressão sanguínea foram avaliadas. A SMet foi classificada de acordo com a Federação Internacional de Diabetes (IDF) (2007). Após o tratamento, os voluntários foram divididos de acordo com os níveis de plasma do ANP aumento (n=31) ou ANP redução (n=19).. Ambos os grupos apresentaram redução significativa de peso corporal, índice de massa corporal (IMC) e circunferências de cintura, pescoço e quadril (CC, CP e CQ, respectivamente), e aumento da massa livre de gordura (MLG). É interessante observar que houve uma redução significativa na gordura corporal, na razão de TG/HDL-c e na prevalência de SMet (de 23% para 6%) somente no grupo com ANP aumento.. Este estudo sugere que o aumento nos níveis séricos de ANP após a terapia para perda de peso pode estar associado a melhorias nos riscos cardiometabólicos e na prevalência reduzida de SMet em adolescentes com obesidade.

Topics: Adolescent; Atrial Natriuretic Factor; Body Composition; Body Mass Index; Cardiovascular Diseases; Child; Humans; Metabolic Syndrome; Pediatric Obesity; Weight Loss

The natriuretic peptides (NPs) system, and mainly atrial natriuretic peptide (ANP), plays a key role in human metabolism and cardiometabolic disorders. Due to differences in NP levels and in prevalence of metabolic syndrome (MetS) between men and women, we aimed to explore the gender difference of association between N-terminal pro-atrial natriuretic peptide (NT-proANP) and MetS in a general population in China.. Participants' weight, height, waist circumference, blood pressure, plasma NT-proANP, and other traditional biomarkers were measured. Multivariate logistic regression models were used to determine the association between plasma NT-proANP and MetS, and the odds ratio (OR) and 95% confidence interval (CI) were calculated for men and women, respectively.. Among 2203 participants, 1361 (61.78%) were women, 687(30.77%) participants had MetS, and the average age was 53 years. Women had a higher level of NT-proANP than men. However, adjusted logistic regression demonstrated that men in the upper quartile group of NT-proANP had 0.60 (95% CI 0.39-0.92) times the risk of having MetS, while women in the upper quartile group had 1.10 (95% CI 0.77-1.56) times the risk of having MetS compared to the lower quartile group. Furthermore, with the increase of the level of NT-proANP, the ORs showed a declining trend in men (P = 0.017), but it was not statistically significant among women (P = 0.700).. There are gender differences in the relationship between NT-proANP and MetS, while an inverse association between plasma NT-proANP and MetS in men suggests that higher levels of NT-proANP may be a protective factor for MetS.

Topics: Adult; Atrial Natriuretic Factor; China; Female; Humans; Male; Metabolic Syndrome; Middle Aged; Protective Factors; Sex Characteristics; Sex Factors

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 middle-aged and elderly populations, circulating natriuretic peptide concentrations are negatively associated with several components of the metabolic syndrome. Whether these negative associations are also present in healthy adolescents and young adults from the general population are unknown.. In a cross-sectional setting, we measured plasma concentrations of mid-regional proatrial natriuretic peptide (MR-proANP) in 343 adolescents (age 14-16 years) and 616 young adults (age 20-28 years) from the Danish site of the European Youth Heart Study, which is a population-based study of cardiovascular disease risk factors in children, adolescents and young adults. We used linear regression analysis to examine the associations, expressed as standardized regression coefficients, of various variables of interest with MR-proANP stratified according to age group, adjusting for age and gender.. Among the young adults, MR-proANP was negatively associated with body mass index (BMI) (β = -0.10, P = 0.02), waist circumference (WC) (β = -0.14, P < 0.001), systolic blood pressure (BP) (β = -0.08, P = 0.03), diastolic BP (β = -0.23, P < 0.001), insulin (β = -0.15, P < 0.001), and triglycerides (β = -0.14, P < 0.001). Among the adolescents a somehow different pattern was observed since MR-proANP was not significantly associated with BMI (β = -0.00, P = 0.98), WC (β = -0.01, P = 0.90) and insulin (β = -0.02, P = 0.69). Nevertheless, among the adolescents, MR-proANP was negatively associated with triglycerides (β = -0.13, P = 0.01), diastolic BP (β = -0.12, P = 0.01) and systolic BP (β = -0.10, P = 0.10), although the latter association was of borderline significance.. The young adults displayed significant negative associations between MR-proANP and several components of the metabolic syndrome, whereas such associations were not found among the adolescents besides triglycerides and diastolic BP.

Topics: Adolescent; Adult; Age Distribution; Age Factors; Atrial Natriuretic Factor; Biomarkers; Blood Pressure; Body Mass Index; Chi-Square Distribution; Cross-Sectional Studies; Denmark; Female; Health Surveys; Humans; Insulin; Linear Models; Male; Metabolic Syndrome; Multivariate Analysis; Sex Distribution; Sex Factors; Triglycerides; Waist Circumference; Young Adult

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

Atrial natriuretic peptide (ANP) is a potent lipolytic agent that acts in adipose tissue. Low levels of ANP might lead to reduced lipolysis and excessive weight gain, which could be one of the biological alterations that contribute to the development of obesity. The aim of the present study was to evaluate the relationship between metabolic syndrome and fasting serum ANP concentrations in older adults.. Fasting blood samples were obtained from 90 older adults. Metabolic syndrome and its components were defined using diagnostic criteria from the International Diabetes Federation.. A total of 40 older adults (44.4%) had metabolic syndrome. Fasting ANP level was negatively correlated with metabolic syndrome (P = 0.015). Univariate linear regression analysis showed that high-density lipoprotein cholesterol (P < 0.001) was positively correlated with serum logANP levels, whereas waist circumference (P = 0.001) and body fat mass (P = 0.002) were negatively correlated with fasting serum logANP levels. Multivariate forward stepwise linear regression analysis of the significant variables showed that high-density lipoprotein cholesterol (β = 0.419, R(2) = 0.268, P < 0.001) and body fat mass (β = -0.396, R(2) = 0.154, P = 0.002) were independent predictors of fasting serum logANP levels in geriatric persons.. Serum ANP levels were reduced in geriatric persons affected by metabolic syndrome. Body fat mass and high-density lipoprotein cholesterol were independent predictors of fasting serum ANP levels in older adults.

Topics: Adiposity; Aged; Atrial Natriuretic Factor; Body Mass Index; Case-Control Studies; Cholesterol, HDL; Fasting; Female; Humans; Male; Metabolic Syndrome; Waist Circumference

Long-acting natriuretic peptide (LANP) is one of the peptide hormones in atrial natriuretic peptide (ANP) prohormone. Its biological properties are blood pressure regulation, maintenance of plasma volume and anticancer effects. The aim of this study was to evaluate the relationship between metabolic syndrome (MetS) and fasting serum LANP concentration in hypertensive patients.. Fasting blood samples were obtained from 224 patients with or without hypertension. MetS and its components were defined using diagnostic criteria from the International Diabetes Federation.. Eighty-eight hypertensive patients (59.5 %) had MetS. Hypertensive patients with MetS had higher body weight (p = 0.003), waist circumference (p = 0.003), body mass index (p = 0.002), triglyceride concentrations (p = 0.029), insulin levels (p = 0.001), HOMA-IR (p <0.003) and HOMA-β (p = 0.049) and lower HDL-C concentrations (p = 0.001), LANP levels (p = 0.012) than those without MetS. The univariable linear regression analysis showed that age (p = 0.038) and the BUN concentration (p = 0.022) were positively correlated with the serum LANP levels, whereas the insulin level (p = 0.001), HOMA-IR (p = 0.004), and HOMA-β (p = 0.001) were negatively correlated with the fasting serum LANP levels among the hypertensive patients. Multivariable forward stepwise linear regression analysis of the significant variables showed that the HOMA-β (β = -0.387, R(2) = 0.141, p <0.001) was an independent predictor of fasting serum LANP levels in hypertensive patients.. LANP level is significantly reduced in hypertensive patients affected by MetS and is negatively related to pancreatic beta cell function in hypertensive patients.

Topics: Aged; Atrial Natriuretic Factor; Blood Pressure; Body Mass Index; Cholesterol, HDL; Cross-Sectional Studies; Fasting; Female; Humans; Hypertension; Insulin; Insulin Resistance; Male; Metabolic Syndrome; Middle Aged; Peptide Fragments; Triglycerides; Waist Circumference

Subjects with metabolic syndrome (MetS) and individuals with type 2 diabetes are at high risk for vascular complications. Hormones acting on vascular endothelium may be involved in the atherogenic process associated with metabolic disorders. The objective of this study was to determine the correlation of pro-atrial natriuretic hormone (proANP) with the presence of subclinical atherosclerosis.. In 1272 subjects participating in the KORA F4 study, we determined plasma levels of mid-regional proANP (MR-proANP) and the intima-media thickness (IMT) of the carotid artery. We used logistic regression models to investigate the relation of MR-proANP with components of MetS and IMT.. In multiple adjusted regression models, MR-proANP levels were inversely associated with MetS (OR = 0.66, 95% CI 0.47-0.93), central obesity (OR = 0.67, 95% CI 0.46-0.96), raised triglyceride levels (OR = 0.53, 95% CI 0.37-0.77), prediabetes (OR = 0.62, 95%, CI 0.44-0.87) and type 2 diabetes (OR = 0.55, 95% CI 0.35-0.88) when comparing the top quartile vs. the lower three quartiles. Furthermore, there was an inverse relationship between MR-proANP and IMT. After adjustment for traditional cardiovascular risk markers, individuals with high MR-proANP plasma levels in the top quartile (Q4) had significantly lower IMT values (Q4 vs. Q1-Q3: β -0.0178, 95% CI -0.0344; -0.0013).. In this population-based study, high plasma concentrations of MR-proANP were significantly associated with a lower incidence of MetS components and lower measures of early atherosclerosis. The data suggest a link between MR-proANP levels and the development of vascular complications.

Topics: Atherosclerosis; Atrial Natriuretic Factor; Automation; Carotid Arteries; Carotid Intima-Media Thickness; Cohort Studies; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Glomerular Filtration Rate; Glucose Tolerance Test; Hormones; Humans; Male; Metabolic Syndrome; Middle Aged; Multivariate Analysis; Peptide Fragments; Regression Analysis; Risk Factors; Triglycerides

To study the effects of a diet rich in salt and/or saturated fat on atrial natriuretic peptide (ANP)-granules, hypertension, renin expression, and cardiac structure in C57Bl/6 mice.. Young adult male mice were separated into four groups (n = 12) and fed one of the following for 9 weeks: standard chow/normal salt (SC-NS), high-fat chow/normal salt (HF-NS), standard chow/high salt (SC-HS) and high-fat chow/high salt (HF-HS). Alterations in the serum ANP, ultrastructural analysis of cardiomyocytes that produce ANP, structural analysis of the left ventricle, blood pressure, renin expression, glomerular filtration rate (GFR), feed efficiency, and lipid and glucose parameters were examined.. The HF-NS diet showed a small increase in ANP production and left ventricular hypertrophy, increased food efficiency, and abnormal lipid and glucose parameters. The SC-HS diet showed a large increase in ANP granules in myocytes and corresponding elevation in ANP serum levels, left ventricular hypertrophy, hypertension, decrease in renin levels, and increase in GFR. The combination of the two diets (HF-HS) had an additive effect.. The incorporation of a high-fat high-salt diet induced ultrastructural changes in cardiomyocytes, increased the production of ANP and increased its serum level, and reduced the amount of renin in the kidney.

Topics: Animals; Atrial Natriuretic Factor; Diet, High-Fat; Dietary Fats; Down-Regulation; Glomerular Filtration Rate; Hypertension; Hypertrophy, Left Ventricular; Kidney; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Myocytes, Cardiac; Random Allocation; Renin; Secretory Vesicles; Sodium Chloride, Dietary; Soybean Oil; Up-Regulation

Urotensin II (UII) exerts multiple effects on the cardiovascular system, acts as a diabetogenic agent, and may also contribute to the development of the metabolic syndrome (MetS). The aim of this study was to determine circulating UII in patients with type 2 diabetes mellitus (T2DM) and its relationship with MetS. A total of 360 consecutive patients with T2DM were included. MetS presence/absence (MetS [+]/[-]) was defined according to American Heart Association/National Heart, Lung and Blood Institute criteria. Plasma concentrations of UII were determined by radioimmunoassay. UII levels were significantly higher in MetS (+) than in MetS (-) T2DM patients (0.97 pg/mL [0.93-1.01], n=294 vs 0.82 pg/mL [0.75-0.88] pg/mL, n=66, respectively; P<.001). Multiple logistic regression analysis showed that UII was significantly associated with MetS (+) (odds ratio, 6.41 [95% confidence interval, 1.21-16.04]; P=.02). UII plasma concentrations are significantly higher in T2DM patients presenting with MetS. Therefore, circulating UII may participate in the worsening course of some T2DM patients and may provide novel therapeutic perspectives.

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Diabetes Mellitus, Type 2; Female; Humans; Logistic Models; Male; Metabolic Syndrome; Middle Aged; Natriuretic Peptide, Brain; Phenotype; Protein Precursors; Retrospective Studies; Urotensins

Urate, a naturally-occurring antioxidant, is a marker/factor for cardiovascular disease. Hyperuricaemia is associated with IR, MetS and endothelial dysfunction. We characterised the associations between neurohormones, uricaemia, and glucose homeostasis in type 2 diabetes mellitus (T2DM) males. Cross-sectional; 705 T2DM males divided into two groups: uric acid < 7.0 mg/dl (normouricaemic; n=476) versus uric acid >or= 7.0 mg/dl (hyperuricaemic; n=229). HOMA beta-cell function (B), insulin sensitivity (S), hyperbolic product (BxS), and (BxS) loss rate were determined alongside neurohormones (Nt-proANP, BNP, Big ET-1 and UII). Mean age and diabetes duration were not different between groups. Hyperuricaemics had more macroangiopathy, total/central adiposity, IR, hypertension, dyslipidemia and MetS prevalence. Nt-proANP and BNP levels were more than twice as high in hyperuricaemics, whereas Big ET-1 and UII were higher by 46% and 14%, respectively. HOMA (BxS) was higher in hyperuricaemics: 31 (16)% vs. 26 (18)% (p=0.0004). BxS loss rate was faster in normouricaemics: 1.36 (0.54)% vs. 1.20 (0.43)%/year(-1) (p<0.0001 ). The proportion with HbA(1C) < 7.0% was 39% (normouricaemics) vs. 49% (hyperuricaemics; p=0.0091). In T2DM males, hyperuricaemia is associated with raised neurohormones together with better beta-cell indices. Urate's dual properties may translate into beneficial (glucose homeostasis) and detrimental (raised neurohormones) effects.

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Blood Glucose; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Endothelin-1; Glycated Hemoglobin; Humans; Hyperuricemia; Insulin; Insulin-Secreting Cells; Male; Metabolic Syndrome; Middle Aged; Natriuretic Peptide, Brain; Up-Regulation; Uric Acid

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

The metabolic syndrome (MS) is associated with left ventricular hypertrophy (LVH). Previous evidence has shown that LVH is favoured by low levels of atrial natriuretic peptide (ANP), independently from blood pressure (BP), in hypertension. Although levels of natriuretic peptides are known to be lower in obesity, plasma ANP levels have not yet been assessed in MS. We aimed to assess the ANP levels and their relationship with left ventricular mass (LVM) in patients affected by MS.. One hundred and twenty-eight essential hypertensive patients were included in the study: 51 with MS and 77 without MS. Clinical, echocardiographical and biochemical parameters, and levels of both N-terminal (NT)-proANP and alphaANP were assessed.. Hypertensive patients affected by MS had higher LVM and increased frequency of LVH. NT-proANP levels were significantly lower in MS, independent of waist circumference (WC). Log(NT-proANP) levels were significantly inversely related to left ventricular mass index (LVMI) (beta = -0.360, P < 0.001) and LVM/height (beta = -0.370, P < 0.001) in the whole hypertensive population by multiple linear regression analysis. The relationship of log(NT-proANP) with LVM was more enhanced in patients with MS.. The present study demonstrates that levels of NT-proANP are significantly reduced in hypertensive patients affected by MS, and they are significantly inversely related to the increased LVM observed in these patients. Our findings, while supporting previous experimental and clinical evidence of the antihypertrophic role of ANP in hypertension, may help to identify one of the possible mechanisms directly underlying LVH in MS.

Topics: Atrial Natriuretic Factor; Biomarkers; Blood Pressure; Case-Control Studies; Echocardiography, Doppler; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Linear Models; Male; Metabolic Syndrome; Middle Aged; Predictive Value of Tests; Protein Precursors; Rome; Stroke Volume; Transforming Growth Factor beta