atrial-natriuretic-factor and Insulin-Resistance

The natriuretic peptide system includes three known peptides: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). They contribute to the regulation of cardiovascular homeostasis through diuretic, natriuretic, and vasodilatory properties. Among them, ANP has received particular attention because of its effects on blood pressure regulation and cardiac function. Although the potential for its therapeutic application in the treatment of hypertension and heart failure has been evaluated in several experimental and clinical investigations, no pharmacological approach directly targeted at modulation of ANP levels has ever reached the stage of being incorporated into clinical practice. Recently, ANP has also received attention as being a possible cardiovascular risk factor, particularly in the context of hypertension, stroke, obesity, and metabolic syndrome. Abnormalities in either peptide levels or peptide structure are thought to underlie its implied role in mediating cardiovascular diseases. Meanwhile, BNP has emerged as a relevant marker of left ventricular (LV) dysfunction and as a useful predictor of future outcome in patients with heart failure. This review deals with the major relevant findings related to the cardiovascular and metabolic effects of natriuretic peptides, to their potential therapeutic use, and to their role in mediating cardiovascular diseases.

Topics: Atrial Natriuretic Factor; Biomarkers; Blood Pressure; Blood Vessels; Cardiovascular Diseases; Fibrosis; Humans; Inflammation; Insulin Resistance; Lipid Metabolism; Myocardium; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Natriuretic Peptides; Risk Factors; Ventricular Dysfunction, Left; Ventricular Remodeling

Topics: Animals; Atrial Natriuretic Factor; Calmodulin-Binding Proteins; Disease Models, Animal; Genetic Predisposition to Disease; Humans; Hypertension; Insulin Resistance; Mutation; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Quantitative Trait Loci; Rats; Receptors, Adrenergic, beta; Renin-Angiotensin System

Topics: Atrial Natriuretic Factor; Autonomic Nervous System; Blood Coagulation Disorders; Bradykinin; Cardiac Output; Diastole; Endothelins; Endothelium, Vascular; Female; Genetic Predisposition to Disease; Humans; Hypertension; Insulin Resistance; Pregnancy; Prenatal Exposure Delayed Effects; Renin-Angiotensin System; Vascular Resistance

The cause of primary (essential) hypertension remains unknown, but a number of circulating hormones and endothelium-derived factors are probably involved. This review summarizes recent evidence on the roles of hyperinsulinemia, the renin-angiotensin system, atrial natriuretic factor, and three endothelium-derived factors--prostacyclin, endothelium-derived relaxing factor, and endothelin.

Topics: Animals; Atrial Natriuretic Factor; Epoprostenol; Hormones; Humans; Hyperinsulinism; Hypertension; Insulin Resistance; Models, Biological; Muscles; Nitric Oxide; Renin-Angiotensin System

Topics: Animals; Atrial Natriuretic Factor; Catecholamines; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Retinopathy; Humans; Hypertension; Insulin Resistance; Renin-Angiotensin System; 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

Plasma concentrations of pro-Atrial natriuretic peptide, proANP, are decreased in obesity and diabetes. Decreased proANP concentrations have also been noted after meal intake, and recently, a glucose-mediated regulation of ANP gene expression was reported. Hence, we evaluated the effects of insulin, glucagon and glucose on plasma proANP in a series of observational and experimental studies. Six healthy men underwent seven days of bed rest. Before and after the bed rest, hyperinsulinemic euglycemic clamps with serial plasma measurements of proANP were performed. Moreover, plasma proANP was quantified in 65 individuals with normal or impaired glucose regulation. Finally, the effects of infusion-induced hyperglucagonemia were examined in ten healthy men. Bed rest decreased insulin sensitivity and plasma proANP. The decrease in proANP was not associated with insulin sensitivity and the peptide concentrations remained constant during euglycemic hyperinsulinemia and hyperglycemic hyperglucagonemia. Impaired glucose regulation was not associated with decreased proANP concentrations. Bed rest per se induces a marked decrease in plasma proANP concentrations whereas insulin resistance and impaired glucose regulation was not associated with lower proANP concentrations. Neither acute hyperinsulinemia nor hyperglucagonemia seems to affect plasma proANP. Our findings thus suggest that decreased plasma proANP concentrations occur late in the development of insulin resistance.

Topics: Adult; Atrial Natriuretic Factor; Bed Rest; Blood Glucose; Humans; Insulin; Insulin Resistance; Male

In 2243 subjects, MR-proANP was measured at baseline. At follow up, MR-proANP levels in the high normal range were associated with lower prevalence of insulin resistance and higher post challenge GIP secretion.

Topics: Atrial Natriuretic Factor; Biomarkers; Female; Heart Failure; Humans; Insulin Resistance; Male; Middle Aged; Prevalence; Prospective Studies; Reference Values

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

The relationship between atrial natriuretic peptide (ANP), increased free fatty acid (FFA) and insulin resistance in patients with mitral valve disease (MVD), a group characterised by elevated atrial pressure and increased ANP levels, is not defined. The present study was performed to evaluate, in MVD patients, the relationship between increased ANP and FFA levels and insulin resistance and the role of mitral valve replacement/repair in ameliorating these metabolic alterations. Conversely, coronary heart disease (CHD) patients were evaluated before and after coronary artery bypass grafting (CABG), since they are known to be insulin resistant in the presence of chronic FFA increase.. Fifty MVD patients and 55 CHD patients were studied before and 2 months after surgery and compared with 166 normal subjects. Before surgery, 56% of MVD patients had impaired glucose tolerance or newly diagnosed type 2 diabetes after a standard oral glucose load and this percentage decreased to 46% after surgery. In CHD, impaired glucose tolerance (IGT) or newly diagnosed type 2 diabetic patients were 67% of patients before and after CABG. In MVD, left atrial (LA) volume, ANP, FFA incremental area and insulin levels were higher and Insulin Sensitivity (IS) index significantly reduced while after surgery, LA volume, ANP and FFA significantly decreased and IS index significantly improved. In CHD, insulin resistance and hyperinsulinaemia were present both before and after surgery with increased tumour necrosis factor (TNF)-α and interleukin (IL)-6 levels.. In MVD, a higher degree of abnormal glucose tolerance and insulin resistance are associated to increased levels of ANP and FFA, while these metabolic alterations are improved by mitral valve replacement/repair surgery. Clinical Trial.gov registration number NCT 00520962.

Topics: Aged; Atrial Natriuretic Factor; Coronary Artery Bypass; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Female; Glucose Intolerance; Heart Valve Diseases; Humans; Insulin Resistance; Interleukin-6; Male; Middle Aged; Mitral Valve; Regression Analysis; Tumor Necrosis Factor-alpha

beta-Receptor blockers may exert a spectrum of metabolic and humoral effects, which might differ depending on the specific adrenoreceptor characteristics of the individual agents. We investigated the influence of celiprolol, a beta 1-blocker with beta 2-agonistic and, possibly, additional weak alpha-receptor antagonistic properties, on insulin sensitivity (SI), glucose homeostasis, and lipid profile in 20 young, healthy, normotensive individuals. SI, fasting plasma glucose and insulin, serum total triglycerides (TG), lipoprotein cholesterol (C) fractions, lipoprotein a [Lp(a)], and plasma atrial natriuretic factor (ANF) levels were determined before and after acute glucose loading under placebo conditions and after 3 weeks of celiprolol administration. The participants were instructed to follow a 3-day standard diet (2,500 kcal/day, 45% carbohydrates, 40% fat, and 15% protein) and an overnight fast before measurements were recorded. As compared with control values, SI, fasting plasma glucose and insulin, the areas under the glucose and insulin curves, the k value of glucose disappearance after glucose load, and serum cholesterol fractions, TG, and Lp(a) were unchanged during celiprolol administration. However, celiprolol significantly reduced plasma ANF levels (p < 0.02). The latter increased in response to acute hyperglycemia/hyperinsulinemia with placebo (p < 0.05) but not with celiprolol. Although diastolic blood pressure (DBP) decreased slightly during the first and second week of celiprolol administration, BP and heart rate (HR) did not differ significantly after 3 weeks on celiprolol treatment as compared with placebo conditions. Our findings demonstrate that in healthy lean humans beta-receptor modulation with celiprolol is neutral with regard to SI and lipoprotein metabolism. Moreover, glucose loading stimulates whereas celiprolol decreases plasma ANF levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenergic beta-1 Receptor Antagonists; Adrenergic beta-Antagonists; Adult; Atrial Natriuretic Factor; Blood Glucose; Body Weight; Celiprolol; Creatinine; Female; Glucose; Humans; Insulin; Insulin Resistance; Lipoproteins; Male; Patient Compliance; Receptors, Adrenergic, beta-2; Sensitivity and Specificity; Sodium

To assess the efficacy and safety of different doses of the alpha-1 blocker terazosin on long-term therapy, 12 essential hypertensives (7 males, 5 females, aged 27-61) were investigated. The study was conducted according to the Latin square design and each patient underwent 4 periods of treatment with 2, 5, 10 mg/day terazosin and placebo, in a double-blind, randomized order. Each treatment lasted 4 weeks. In comparison to placebo, a fall in diastolic pressure was observed already with the 2 mg/daily dose, with a decrease > 10 mmHg in 7 patients (responders). Body weight increased in a dose dependent manner, while atrial natriuretic peptide, serum glucose and insulin during oral glucose tolerance test, total cholesterol, HDL and LDL cholesterol, triglycerides were unaffected. It is concluded that terazosin is effective and safe in essential hypertensives already at 2 mg daily dose. Further reduction in blood pressure at higher doses is likely to be counteracted by salt and water retention.

Topics: Adrenergic alpha-Antagonists; Adult; Atrial Natriuretic Factor; Blood Glucose; Double-Blind Method; Female; Humans; Hypertension; Insulin Resistance; Lipids; Male; Middle Aged; Prazosin

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

Increasing evidence suggests natriuretic peptides (NPs) coordinate inter-organ metabolic crosstalk with adipose tissues and play a critical role in energy metabolism. We recently reported A-type NP (ANP) raises intracellular temperature in cultured adipocytes in a low-temperature-sensitive manner. We herein investigated whether exogenous ANP-treatment exerts a significant impact on adipose tissues in vivo. Mice fed a high-fat-diet (HFD) or normal-fat-diet (NFD) for 13 weeks were treated with or without ANP infusion subcutaneously for another 3 weeks. ANP-treatment significantly ameliorated HFD-induced insulin resistance. HFD increased brown adipose tissue (BAT) cell size with the accumulation of lipid droplets (whitening), which was suppressed by ANP-treatment (re-browning). Furthermore, HFD induced enlarged lipid droplets in inguinal white adipose tissue (iWAT), crown-like structures in epididymal WAT, and hepatic steatosis, all of which were substantially attenuated by ANP-treatment. Likewise, ANP-treatment markedly increased UCP1 expression, a specific marker of BAT, in iWAT (browning). ANP also further increased UCP1 expression in BAT with NFD. Accordingly, cold tolerance test demonstrated ANP-treated mice were tolerant to cold exposure. In summary, exogenous ANP administration ameliorates HFD-induced insulin resistance by attenuating hepatic steatosis and by inducing adipose tissue browning (activation of the adipose tissue thermogenic program), leading to in vivo thermogenesis during cold exposure.

Topics: Adipose Tissue, Brown; Adipose Tissue, White; Animals; Atrial Natriuretic Factor; Diet, High-Fat; Energy Metabolism; Fatty Liver; Glucose Intolerance; Insulin Resistance; Male; Mice; Mice, Inbred C57BL; Thermogenesis

Increased myocardial autophagy has been established as an important stress-induced cardioprotective response. Three weeks after generating cardiomyocyte-specific autophagy deficiency, via inducible deletion of autophagy-related protein 7 (Atg7), we found that these mice (AKO) had increased body weight and fat mass without altered food intake. Glucose and insulin tolerance tests indicated reduced insulin sensitivity in AKO mice. Metabolic cage analysis showed reduced ambulatory activity and oxygen consumption with a trend of elevated respiratory exchange ratio in AKO mice. Direct analysis of metabolism in subcutaneous and visceral adipocytes showed increased glucose oxidation and reduced ATGL expression and HSL phosphorylation with no change in lipid synthesis or fatty acid oxidation. Importantly, we found AKO mice had reduced myocardial and circulating levels of atrial natriuretic peptide (ANP), an established mediator of myocardial-adipose cross talk. When normal ANP levels were restored to AKO mice with use of osmotic pump, the metabolic dysfunction evident in AKO mice was corrected. We conclude that cardiac autophagy deficiency alters myocardial-adipose cross talk via decreased ANP levels with adverse metabolic consequences.

Topics: Adipocytes; Adipose Tissue; Animals; Atrial Natriuretic Factor; Autophagy; Autophagy-Related Protein 7; Glucose; Insulin; Insulin Resistance; Mice; Mice, Knockout; Myocardium; Palmitates; Phosphorylation

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

Higher levels of brain natriuretic peptide (BNP) have been associated with a decreased risk of diabetes in adults, but whether BNP is related to insulin resistance in older adults has not been established.. N-terminal of the pro hormone brain natriuretic peptide (NT-pro BNP) was measured among Cardiovascular Health Study participants at the 1989-1990, 1992-1993 and 1996-1997 examinations. We calculated measures of insulin resistance [homeostatic model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), Gutt index, Matsuda index] from fasting and 2-h concentrations of glucose and insulin among 3318 individuals with at least one measure of NT-proBNP and free of heart failure, coronary heart disease and chronic kidney disease, and not taking diabetes medication. We used generalized estimating equations to assess the cross-sectional association of NT-proBNP with measures of insulin resistance. Instrumental variable analysis with an allele score derived from nine genetic variants (single nucleotide polymorphisms) within or near the NPPA and NPPB loci was used to estimate an un-confounded association of NT-proBNP levels on insulin resistance.. Lower NT-proBNP levels were associated with higher insulin resistance even after adjustment for BMI, waist circumference and other risk factors (P < 0.001 for all four indices). Although the genetic score was strongly related to measured NT-proBNP levels amongst European Americans (F statistic = 71.08), we observed no association of genetically determined NT-proBNP with insulin resistance (P = 0.38; P = 0.01 for comparison with the association of measured levels of NT-proBNP).. In older adults, lower NT-proBNP is associated with higher insulin resistance, even after adjustment for traditional risk factors. Because related genetic variants were not associated with insulin resistance, the causal nature of this association will require future study.

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Black or African American; Blood Glucose; Cross-Sectional Studies; Fasting; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Male; Natriuretic Peptide, Brain; Peptide Fragments; Polymorphism, Single Nucleotide; White People

Topics: Atrial Natriuretic Factor; Humans; Insulin; Insulin Resistance; Natriuretic Peptide, Brain; Natriuretic Peptides

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

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

It is believed that a dysfunction in adipose tissue plays an important role in the pathogenesis of polycystic ovary syndrome (PCOS). Natriuretic peptides are hormones that regulate cardiovascular and body fluid homeostasis and adipose tissue metabolism. Natriuretic peptide levels are reduced in individuals with obesity and diabetes.. This study aimed to investigate whether natriuretic peptide levels are altered in women with PCOS and whether they correlate with adiponectin levels or insulin sensitivity markers.. This was a cross-sectional study at a referral center in a teaching hospital.. We evaluated 40 patients diagnosed with PCOS according to the Rotterdam criteria and 36 control women matched for age and body mass index.. We measured serum adiponectin, plasma atrial natriuretic peptide (ANP), and plasma brain natriuretic peptide using enzyme immunoassays in both groups. We evaluated metabolic markers, such as fasting glucose, insulin, total cholesterol, high-density lipoprotein, low-density lipoprotein, and triglycerides. In addition, we calculated the homeostasis model assessment for insulin resistance index (HOMA-IR) and the lipid accumulation product (LAP) index and tested the linear correlations between these metabolic indices and the plasma ANP and serum adiponectin concentrations.. ANP and adiponectin were reduced in the PCOS group compared with the control group (P = 0.010 and P = 0.014, respectively). The brain natriuretic peptide concentration did not differ between the two groups (P = 0.883). There was no correlation between ANP and any of the metabolic markers. In the control group, the serum adiponectin level was inversely correlated with BMI (P = 0.011), waist circumference (P = 0.021), insulin (P = 0.013), fasting glucose (P = 0.010), homeostasis model assessment for insulin resistance index (P = 0.007), and lipid accumulation product (P = 0.022). Remarkably, none of these correlations were observed in the women with PCOS.. Women with PCOS had lower ANP and adiponectin compared with controls matched for age and BMI. Thus, the mechanisms that affect ANP and adiponectin production and clearance may be altered in PCOS, regardless of adiposity. These hormones may be involved in the metabolic features of PCOS.

Topics: Adiponectin; Adiposity; Adult; Atrial Natriuretic Factor; Biomarkers; Body Mass Index; Cross-Sectional Studies; Down-Regulation; Female; Hospitals, Teaching; Humans; Insulin Resistance; Lipid Metabolism; Natriuretic Peptide, Brain; Overweight; Polycystic Ovary Syndrome

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

Atrial natriuretic peptide (ANP) has been shown to regulate lipid and carbohydrate metabolism providing a possible link between cardiovascular function and metabolism by mediating the switch from carbohydrate to lipid mobilization and oxidation. ANP exerts a potent lipolytic effect via cGMP-dependent protein kinase (cGK)-I mediated-stimulation of AMP-activated protein kinase (AMPK). Activation of the ANP/cGK signaling cascade also promotes muscle mitochondrial biogenesis and fat oxidation. Here we demonstrate that ANP regulates lipid metabolism and oxygen utilization in differentiated human adipocytes by activating the alpha2 subunit of AMPK. ANP treatment increased lipolysis by seven fold and oxygen consumption by two fold, both of which were attenuated by inhibition of AMPK activity. ANP-induced lipolysis was shown to be mediated by the alpha2 subunit of AMPK as introduction of dominant-negative alpha2 subunit of AMPK attenuated ANP effects on lipolysis. ANP-induced activation of AMPK enhanced mitochondrial oxidative capacity as evidenced by a two fold increase in oxygen consumption and induction of mitochondrial genes, including carnitine palmitoyltransferase 1A (CPT1a) by 1.4-fold, cytochrome C (CytC) by 1.3-fold, and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) by 1.4-fold. Treatment of human adipocytes with fatty acids and tumor necrosis factor α (TNFα) induced insulin resistance and down-regulation of mitochondrial genes, which was restored by ANP treatment. These results show that ANP regulates lipid catabolism and enhances energy dissipation through AMPK activation in human adipocytes.

Topics: Adipocytes; AMP-Activated Protein Kinases; Atrial Natriuretic Factor; Cells, Cultured; Enzyme Activation; Gene Expression; Genes, Mitochondrial; Humans; Insulin Resistance; Lipid Metabolism; Lipolysis; Oxygen Consumption

Increased adipose tissue secretion of adipokines and cytokines has been implicated in the chronic low-grade inflammation state and insulin resistance associated with obesity. We tested here whether the cardiovascular and metabolic hormone atrial natriuretic peptide (ANP) was able to modulate adipose tissue secretion of several adipokines (derived from adipocytes) and cytokines (derived from adipose tissue macrophages).. We used protein array to measure the secretion of adipokines and cytokines after a 24-h culture of human subcutaneous adipose tissue pieces treated or not with a physiological concentration of ANP. The effect of ANP on protein secretion was also directly studied on isolated adipocytes and macrophages. Gene expression was measured by real-time RT-quantitative PCR.. ANP decreased the secretion of the pro-inflammatory cytokines IL-6 and TNF-alpha, of several chemokines, and of the adipokines leptin and retinol-binding protein-4 (RBP-4). The secretion of the anti-inflammatory molecules IL-10 and adiponectin remained unaffected. The cytokines were mainly expressed in macrophages that expressed all components of the ANP-dependent signalling pathway. The adipokines, leptin, adiponectin and RBP-4 were specifically expressed in mature adipocytes. ANP directly inhibited the secretion of IL-6 and monocyte chemoattractant protein-1 by macrophages. The inhibitory effects of ANP on leptin and growth-related oncogene-alpha secretions were not seen under selective hormone-sensitive lipase inhibition.. We suggest that ANP, either by direct action on adipocytes and macrophages or through activation of adipocyte hormone-sensitive lipase, inhibits the secretion of factors involved in inflammation and insulin resistance.

Topics: Abdomen; Adipocytes; Adiponectin; Adipose Tissue; Adult; Atrial Natriuretic Factor; Cells, Cultured; Cytokines; Female; Humans; Inflammation; Insulin Resistance; Macrophages; Middle Aged; Overweight; Polymerase Chain Reaction; RNA

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

Myocardium undergoing remodeling in vivo exhibits insulin resistance that has been attributed to a shift from the insulin-sensitive glucose transporter GLUT4 to the fetal, less insulin-sensitive, isoform GLUT1. To elucidate the role of altered GLUT4 expression in myocardial insulin resistance, glucose uptake and the expression of the glucose transporter isoforms GLUT4 and GLUT1 were measured in adult rat cardiomyocytes (ARC). ARC in culture spontaneously undergo dedifferentiation, hypertrophy-like spreading, and return to a fetal-like gene expression pattern. Insulin stimulation of 2-deoxy-D-glucose uptake was completely abolished on day 2 and 3 of culture and recovered thereafter. Although GLUT4 protein level was reduced, the time-course of unresponsiveness to insulin did not correlate with altered expression of GLUT1 and GLUT4. However, translocation of GLUT4 to the sarcolemma in response to insulin was completely abolished during transient insulin resistance. Insulin-mediated phosphorylation of Akt was not reduced, indicating that activation of phosphatidylinositol 3-kinase (PI3K) was preserved. On the other hand, total and phosphorylated Cbl was reduced during insulin resistance, suggesting that activation of Cbl/CAP is essential for insulin-mediated GLUT4 translocation, in addition to activation of PI3K. Pharmacological inhibition of contraction in insulin-sensitive ARC reduced insulin sensitivity and lowered phosphorylated Cbl. The results suggest that transient insulin resistance in ARC is related to impairment of GLUT4 translocation. A defect in the PI3K-independent insulin signaling pathway involving Cbl seems to contribute to reduced insulin responsiveness and may be related to contractile arrest.

Topics: Animals; Atrial Natriuretic Factor; Biological Transport, Active; Calcium Channel Blockers; Cell Differentiation; Cell Size; Cells, Cultured; Deoxyglucose; Diacetyl; Enzyme Activation; Gene Expression Regulation; Glucose Transporter Type 1; Glucose Transporter Type 4; Insulin; Insulin Resistance; Monosaccharide Transport Proteins; Muscle Proteins; Myocardial Contraction; Myocytes, Cardiac; Phosphatidylinositol 3-Kinases; Phosphorylation; Protein Processing, Post-Translational; Protein Serine-Threonine Kinases; Protein Transport; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-cbl; Rats; RNA, Messenger; Sarcolemma; Ubiquitin-Protein Ligases; Verapamil

In hypertensive patients, diminished nocturnal blood pressure (BP) fall is associated with poor prognosis for cardiovascular events. However, the relation of insulin resistance with the etiology of nondipper essential hypertension remains unclear. The aim of the present study was to assess the role of insulin resistance in diminished nocturnal BP fall, left ventricular hypertrophy (LVH), and increased plasma atrial (ANP) and brain natriuretic peptides (BNP) in essential hypertensive patients. One hundred and three patients with essential hypertension were divided into dippers (n = 57; age: 57 +/- 5 years, mean +/- SD) or age-matched nondippers (n = 46; 57 +/- 4 years), based on ambulatory BP (ABP) monitoring. Although the systolic and diastolic ABP values were similar during the day, those at night were higher in nondippers than in dippers ( p < 0.0001 for each). Echocardiographic findings revealed that the left ventricular mass index (LVMI) was higher in nondippers (p < 0.0001). Plasma ANP and BNP were also higher in nondippers (p < 0.0001 for each). Fasting plasma concentrations of glucose and insulin (p < 0.0001 for each) and the homeostasis model assessment (HOMA) index (p < 0.0001) were also higher in nondippers. Multivariate analysis revealed that systolic ABP at night was a significant factor for LVMI, ANP and BNP. In addition, the HOMA index was a significant factor for LVMI and BNP. These observations suggest that diminished nocturnal BP fall is closely related to the development of LVH with concomitant increase in BNP in essential hypertensive patients, and that insulin resistance may play a key role in these processes.

Topics: Atrial Natriuretic Factor; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Case-Control Studies; Circadian Rhythm; Echocardiography; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Insulin Resistance; Male; Middle Aged; Natriuretic Peptide, Brain

A fructose-enriched diet induces an increase in blood pressure associated with metabolic alterations in rats. Our hypothesis was that an increase in protein kinase C (PKC) activation, reported in the acute period of fructose overload, and an impaired vessel's response to vasoactive substances contribute to maintain elevated blood pressure levels in the chronic period. The aims of this study were to investigate in this animal model of hypertension: (1) if the increase in PKC activation was also found in the chronic stage; (2) the involvement of nitric oxide and insulin in the vessel's response; and plasma atrial natriuretic factor and nitrites/nitrates (nitric oxide metabolites) behavior. We evaluated the effects of: PKC-stimulator 12,13-phorbol dibutyrate, phenylephrine, insulin, nitric oxide synthase-inhibitor NG-nitro-L-arginine methyl esther (L-NAME) and PKC-inhibitor Calphostin C on aortic rings responses of Sprague-Dawley rats: fructose-fed and control. The fructose-fed group showed higher contractility to 12,13-phorbol dibutyrate than the control group in aortic rings pre-incubated with insulin, and this difference disappeared with L-NAME. The response to phenylephrine in rings pre-incubated with Calphostin C was decreased in the fructose-fed group and increased with Calphostin C plus L-NAME. Fructose-fed rats showed higher levels of plasma atrial natriuretic factor and nitrites/nitrates than controls. In conclusion, chronic fructose feeding seems to develop an impaired response to insulin, dependent on nitric oxide, suggesting a PKC alteration. Vasorelaxant agents, such as atrial natriuretic factor and nitric oxide, would behave as compensatory mechanisms in response to high blood pressure.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Enzyme Activators; Enzyme Inhibitors; Fructose; Hypertension; Hypoglycemic Agents; Insulin; Insulin Resistance; Male; Muscle Contraction; Muscle, Smooth, Vascular; Naphthalenes; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Phorbol 12,13-Dibutyrate; Protein Kinase C; Rats; Rats, Sprague-Dawley

Pioneer studies have proposed that multiple metabolic abnormalities, such as insulin resistance, increased Na(+)-H(+) exchanger activity and abnormal intracellular calcium homeostasis, are frequently associated with a subset of essential hypertensive patients with low plasma renin activity (PRA). However, it is unclear whether insulin resistance is related to the low renin status in the very early phase of genetical hypertension. Besides, there is controversy on the subject of the in vivo effect of acute hyperinsulinaemia on sodium-related factors. We investigated the relationship between sodium-related parameters and insulin sensitivity, and the effects of euglycaemic hyperinsulinaemia on cyclic guanosine monophosphate (cGMP) and atrial natriuretic peptide (ANP) levels in 17 young, lean, normotensive male subjects, who displayed extreme predispositions for the development of hypertension. PRA was significantly lower in the positive than in the negative family history group (P < 0.05). Insulin sensitivity (M-value) was correlated with PRA before euglycaemic hyperinsulinaemic clamping (r = 0.577, P < 0.05), and was also inversely correlated with fractional excretion of sodium (FE(Na)) before clamping (r = -0.51, P < 0.05). Euglycaemic hyperinsulinaemia significantly decreased PRA (P < 0.0001) and increased cGMP (P < 0.05) and ANP levels (P < 0.01). In conclusion, insulin sensitivity may be partially determined by PRA levels and FE(Na) before clamping in young, lean, normotensive male subjects. Acute euglycaemic hyperinsulinaemia decreases PRA, and increases cGMP and ANP levels from the fasting condition.

Topics: Adult; Atrial Natriuretic Factor; Cyclic GMP; Glucose Clamp Technique; Homeostasis; Humans; Hyperinsulinism; Hypertension; Insulin Resistance; Male; Predictive Value of Tests; Renin; Sensitivity and Specificity; Sodium; Thinness

To clarify the association between the actions of insulin on the vascular wall and on the muscles in diabetes, we evaluated insulin-mediated vasodilation and muscle glucose uptake simultaneously using the euglycemic hyperinsulinemic glucose clamp technique and the calculation of total peripheral vascular resistance (TPR) from arterial pulse wave analysis in 19 Japanese patients with type 2 diabetes who had no signs of atherosclerosis. During the clamp study, the plasma norepinephrine (NE) level and plasma renin activity (PRA) increased without showing any significant correlation to the glucose infusion rate (GIR); a marker of muscle insulin sensitivity, and no changes of other plasma vasoactive hormone levels were observed. TPR decreased over time during the clamp study. The decrease of TPR from baseline was 0.88 +/- 0.02 at 1 h (mean +/- S.E.M., P < 0.01) and 0.79 +/- 0.03 at 2 h (P < 0.01), and the relative change in TPR from baseline was negatively correlated with GIR (r = -0.48 at 1 and 2 h; both P < 0.05). Our results suggest that there is also insulin resistance in the vascular wall, and this phenomenon may be associated with muscle insulin resistance in type 2 diabetes.

Topics: Adult; Atrial Natriuretic Factor; Blood Glucose; Diabetes Mellitus, Type 2; Endothelin-1; Female; Glucose Clamp Technique; Humans; Infusions, Intravenous; Insulin; Insulin Resistance; Male; Muscle, Skeletal; Norepinephrine; Regression Analysis; Renin; Sodium; Vascular Resistance; Vasodilation

Non-insulin-dependent diabetes mellitus (NIDDM) is characterized by insulin resistance hyperinsulinaemia and a high frequency of hypertension. It has recently been shown that insulin exerts a sodium-retaining effect, which is preserved in NIDDM: We sought to determine whether insulin affected renal sodium handling differently in hypertensive and normotensive NIDDM patients.. After a baseline period of 2 h, eight normotensive (N-) NIDDM patients and eight NIDDM patients with hypertension (H-) underwent a euglycaemic clamp with infusion of two sequential doses of insulin (50 and 500 mU/kg/h) or vehicle (time control) during 2-h periods each. Fractional clearances of sodium and lithium were determined according to standard methods. Fractional lithium clearance was used to assess segmental tubular sodium handling.. Insulin induced similar decrements in fractional sodium excretion (N-NIDDM: 43+/-5.9 and 57+/-9.1%,H-N IDDM: 48+/-16.4 and 62+/-12.5%, low and high insulin dose respectively). Distal tubular sodium absorption increased simultaneously. A fall in fractional proximal sodium reabsorption was observed in N-NIDDM (4.4+/-2.7 and 29.8+/-5.1%, low and high insulin dose respectively), which was attenuated in H-NIDDM (-5.0+/-7.3 and -2.1+/-13.9% respectively). The latter appeared to be related to a defective atrial natriuretic factor (ANF) and renal cyclic GMP response. A modest decrease in blood pressure occurred during insulin infusion that was not related to changes in ANF or FeLi.. The findings suggest that insulin-induced sodium retention may contribute to hypertension in NIDDM if the homeostatic response to offset this effect fails.

Topics: Atrial Natriuretic Factor; Blood Pressure; Cardiovascular System; Case-Control Studies; Cyclic GMP; Diabetes Mellitus, Type 2; Female; Humans; Hypertension; Insulin; Insulin Resistance; Kidney; Male; Middle Aged; Natriuresis; Renin

Impaired renal sodium excretion and increased plasma atrial natriuretic peptide (ANP) levels have been reported in patients with hypertension associated with insulin resistance and hyperinsulinemia. To clarify the interrelationship between hyperinsulinemia and plasma natriuretic peptides, we investigated the effects of physiological and non-physiological hyperinsulinemia on the plasma ANP and brain natriuretic peptide (BNP) levels. Plasma immunoreactive insulin (IRI), ANP and BNP levels were determined by a euglycemic-hyperinsulinemic glucose clamp in 20 patients with non-insulin-dependent diabetes mellitus, by a glucose challenge test in 22 normal subjects and by an insulin challenge test in six normal subjects. Both in the glucose clamp and the glucose challenge test, plasma ANP showed a significant increase in association with increased plasma IRI and plasma volume. However, there was no significant correlation between the changes in plasma ANP levels and plasma IRI levels in view of the peak values and the area under the curve of their responses. In addition, the plasma ANP did not show any significant change despite the marked elevation of plasma IRI in the insulin challenge test. There was no significant change in plasma BNP under any of the hyperinsulinemic conditions. These findings provide in vivo evidence for the lack of a direct effect of acute hyperinsulinemia on natriuretic peptides, although the chronic effects of hyperinsulinemia remain to be elucidated.

Topics: Acute Disease; Adult; Atrial Natriuretic Factor; Blood Glucose; Diabetes Mellitus, Type 2; Female; Glucose; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins

Insulin-stimulated peripheral glucose uptake and insulin-induced renal tubular sodium reabsorption were investigated in normotensive men with a family history of hypertension (relatives, n = 35) compared with age- and body mass index-matched normotensive men with no family history of hypertension (controls, n = 23). The effect of insulin on the renin-aldosterone system was also studied. The euglycemic hyperinsulinemic clamp technique was used to measure peripheral glucose uptake (insulin sensitivity index). Renal clearance of 51Cr-labeled EDTA, sodium, and lithium was used to calculate fractional excretion of sodium and fractional proximal and distal tubular reabsorption of sodium before and during insulin infusion. The insulin sensitivity index was lower in relatives than in controls. Fractional excretion of sodium was reduced, and fractional proximal and distal tubular reabsorption of sodium were increased to the same extent in both groups during insulin infusion. Fractional distal tubular reabsorption of sodium was positively correlated to the reduction of serum potassium in all individuals. Plasma renin activity increased to the same extent in both groups, whereas plasma aldosterone was reduced only in controls. In conclusion, the impaired insulin-stimulated glucose uptake in peripheral tissues in normotensive sons of hypertensive families was accompanied by retained insulin-induced tubular sodium reabsorption. The lack of suppression of aldosterone secretion in these individuals may enhance sodium retention.

Topics: Absorption; Adult; Atrial Natriuretic Factor; Blood Pressure; Humans; Hypertension; Insulin; Insulin Resistance; Kidney; Male; Middle Aged; Renal Circulation; Renin; Sodium

Hyperinsulinemia and insulin resistance are implicated in the etiology of hypertension, but the mechanisms involved have not been established. The objectives of this study were to determine whether untreated essential hypertensive patients are more sensitive to the antinatriuretic action of insulin and more resistant to the counteracting natriuretic effect of atrial natriuretic peptide in contrast to age- and sex-matched normotensive control subjects. Urinary sodium excretion was measured at baseline, during hyperinsulinemic euglycemic clamp, and during coadministration of insulin and atrial natriuretic peptide. Baseline urinary sodium excretion was not significantly different in the normotensive subjects (415 +/- 47 mumol/min, n = 12) and hypertensive patients (381 +/- 18 mumol/min, n = 10); with the institution of insulin infusion, there was a similar and significant decline from baseline (P < .001) to 289 +/- 35 mumol/min in normotensive subjects and 235 +/- 17 mumol/min in hypertensive patients. Atrial natriuretic peptide was able to oppose the antinatriuretic action of insulin in normotensive subjects, increasing urinary sodium excretion significantly to a mean level of 352 +/- 31 mumol/min (P < .05), which did not differ significantly from baseline. In the hypertensive group, atrial natriuretic peptide infusion had no effect on urinary sodium excretion (238 +/- 18 mumol/min), and the difference from baseline remained highly significant (P < .001). The hypertensive patients were significantly less insulin sensitive than their normotensive counterparts, as reflected by a lower glucose utilization rate and higher mean baseline plasma insulin level (P < .05 for each).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Atrial Natriuretic Factor; Glucose Clamp Technique; Hemodynamics; Humans; Hypertension; Insulin; Insulin Resistance; Kidney Tubules; Male; Middle Aged; Natriuresis; Renal Circulation; Sodium