Modulation of renin angiotensin system components by high glucose levels in the culture of collecting duct cells.

Diabetes mellitus and its complications have become a major health concern in Western countries. Increased activity of the intrarenal renin-angiotensin system (RAS) contributes to diabetic nephropathy (DN). We previously reported that in mesangial cells, the high glucose concentration (HG) leads to upregulation of angiotensin-converting enzyme (ACE) messenger RNA, suggesting that ACE was modulated by angiotensin II (Ang II) release. However, this relation in the collecting duct has not yet been studied. We, therefore, aimed to evaluate RAS modulation in inner medullary collecting duct cells (IMCD) exposed to HG. The IMCD were divided into normal glucose (5 mM D-glucose, NG), high glucose (30 mM, HG), and mannitol (30 mM, M) groups. The cells were cultured 48 hr in their respective media. The intracellular and extracellular ACE activity was measured using hippuryl-His-Leu as substrate via a fluorimetric assay and expression was analyzed using western blot analysis. ACE activity, intracellular (27%) and extracellular (22%), was significantly lower in the HG group than in NG and M. ACE2 activity and Ang 1-7 levels were higher in the intracellular compartment. Our data suggest that the HG cannot modify ACE synthesis in IMCD cells but can modulate its activity. The decrease in ACE activity may result in decreased levels of Ang II to protect the IMCD against proliferative and inflammatory deleterious effects of this peptide. Conversely, the increase of ACE2 generating high levels of Ang 1-7, a vasodilator peptide, suggesting that this peptide can induce glucose uptake and protect cells against oxidative stress, which can elicit insulin resistance.

Timing of fructose intake: an important regulator of adiposity.

1. Overconsumption of fructose produces glucose intolerance, autonomic abnormalities and renal dysfunction and may be related to the worldwide epidemic of obesity and diabetes. 2. Experiments were conducted to determine whether the time period (light or dark) of fructose consumption influenced the pathological consequences. C57BL mice were given standard chow and assigned to one of three groups: (i) control (n = 10), which received water over a 24 h period; (ii) FL (n = 11), which received 10% fructose solution during the 12 h light period; and (iii) FD (n = 11), which received 10% fructose solution during the 12 h dark period. 3. There was a time related increase in body weight for all groups (P < 0.01, 2 vs 6 wks). There was a greater increase in body fat in the FL group compared with the control and FD groups. The changes in adiposity occurred even though the total caloric intake was not significantly different among the groups (approximately 18 kcal/day). Total fluid (water + fructose) consumption was greater in the FD and FL groups compared with control at 6 weeks. Significant increases were noted for plasma insulin and leptin at 8 weeks, with highest levels in the FL compared with FD group (P < 0.05). There were no significant changes in glucose, glucose tolerance, cholesterol, triglycerides or adiponectin. 4. The results of the present study suggest that there is a mismatch in caloric consumption, metabolism and adiposity as related to the light-dark cycle of fructose consumption. These findings have clinical implications in the control of bodyweight, abdominal fat accumulation and Type 2 diabetes.

Wistar rat as an animal model to study high-fat induced kidney damage: a systematic review.

The effects of high-fat-associated kidney damage in humans are not completely elucidated. Animal experiments are essential to understanding the mechanisms underlying human diseases. This systematic review aimed to compile evidence of the role of a high-fat diet during the development of renal lipotoxicity and fibrosis of Wistar rats to understand whether this is a satisfactory model for the study of high fat-induced kidney damage. We conducted systematic searches in PUBMED, EMBASE, Lilacs, and Web of Science databases from inception until May 2021. The risk of bias was assessed using SYRCLE toll. Two reviewers independently screened abstracts and reviewed full-text articles. A total of 11 studies were included. The damage varied depending on the age and sex of the animals, time of protocol, and amount of fat in the diet. In conclusion, the Wistar rat is an adequate animal model to assess the effects of a high-fat diet on the kidneys.HighlightsA high-fat diet may promote kidney damage in Wistar rats.Wistar rat is efficient as an animal model to study high-fat-induced kidney damage.The effect of the diet depends on the fat amount, consumption time, and animal age.

Reduction of oxidative stress and inflammatory signaling in the commissural nucleus of the solitary tract (commNTS) and rostral ventrolateral medulla (RVLM) in treadmill trained rats.

Inflammation has been associated with cardiovascular diseases and the key point is the generation of reactive oxygen species (ROS). Exercise modulates medullary neurons involved in cardiovascular control. We investigated the effect of chronic exercise training (Tr) in treadmill running on gene expression (GE) of ROS and inflammation in commNTS and RVLM neurons. Male Wistar rats (N = 7/group) were submitted to training in a treadmill running (1 h/day, 5 days/wk/10 wks) or maintained sedentary (Sed). Superoxide dismutase (SOD), catalase (CAT), neuroglobin (Ngb), Cytoglobin (Ctb), NADPH oxidase (Nox), cicloxigenase-2 (Cox-2), and neuronal nitric oxide synthase (NOS1) gene expression were evaluated in commNTS and RVLM neurons by qPCR. In RVLM, Tr rats increased Ngb (1.285 ± 0.03 vs. 0.995 ± 0.06), Cygb (1.18 ± 0.02 vs.0.99 ± 0.06), SOD (1.426 ± 0.108 vs. 1.00 ± 0.08), CAT (1.34 ± 0.09 vs. 1.00 ± 0.08); and decreased Nox (0.55 ± 0.146 vs. 1.001 ± 0.08), Cox-2 (0.335 ± 0.05 vs. 1.245 ± 0.02), NOS1 (0.51 ± 0.08 vs. 1.08 ± 0.209) GE compared to Sed. In commNTS, Tr rats increased SOD (1.384 ± 0.13 vs. 0.897 ± 0.101), CAT GE (1.312 ± 0.126 vs. 0.891 ± 0.106) and decreased Cox-2 (0.052 ± 0.011 vs. 1.06 ± 0.207) and NOS1 (0.1550 ± 0.03559 vs. 1.122 ± 0.26) GE compared to Sed. Therefore, GE of proteins of the inflammatory process reduced while GE of antioxidant proteins increased in the commNTS and RVLM after training, suggesting a decrease in oxidative stress of downstream pathways mediated by nitric oxide.

Early consumption of high-fat diet worsens renal damage in spontaneously hypertensive rats in adulthood.

The association between hypertension and obesity has been shown to be an important cause of kidney disease. We aimed to investigate the impact of a high-fat diet (HFD) administered in spontaneously hypertensive rats (SHR) after weaning in renal morphology and functional parameters. Male post-weaned SHR were divided into two groups: standard control diet (CD) (3% lipids; n = 8) or HFD (30% lipids; n = 8) during 8 weeks. The group HFD showed an increase in serum triglycerides (HFD: 96 ± 7 vs. CD: 33 ± 2 mg/dL) and glucose intolerance (HFD: 185 ± 7 vs. CD: 149 ± 4 mg/dL/min). Moreover, the HFD also showed an increase in almost 90% of the periepididymal and retroperitoneal adiposity. There was no difference in arterial blood pressure between groups. Renal morphofunctional parameters were decreased in HFD group for glomerular tuft area and diameter (4733 ± 65 µm2 and 82 ± 1 µm, respectively) when compared with CD group (5289 ± 171 µm2 and 88 ± 2 µm, respectively). HFD also showed a decrease of 50% of the renal function, which was associated with higher renal extracellular matrix and lipid deposition. Therefore, our data suggest that HFD since early period of life may contribute to renal damage in adults with hypertension, and this impairment can be associated with increased renal lipid accumulation.

Post-weaning Exposure to High-Fat Diet Induces Kidney Lipid Accumulation and Function Impairment in Adult Rats.

Aim: We investigated the kidney morphofunctional consequences of high-fat diet intake since post-weaning in adult rats. Main Methods: Male Wistar rats were divided into two groups: ND (normal diet; n = 10) and HD (high-fat diet; n = 10). The high-fat diet was introduced post-weaned and animals were followed for 8 weeks. Key Findings: HD group did not change body weight gain even though food consumption has decreased with no changes in caloric consumption. The HD group showed glucose intolerance and insulin resistance. The glomerular filtration rate (GFR) was decreased in vivo (ND: 2.8 ± 1.01; HD: 1.1 ± 0.14 ml/min) and in the isolated perfusion method (34% of decrease). Renal histological analysis showed a retraction in glomeruli and an increase in kidney lipid deposition (ND: 1.5 ± 0.17 HD: 5.9 ± 0.06%). Furthermore, the high-fat diet consumption increased the pro-inflammatory cytokines IL-6 (ND: 1,276 ± 203; HD: 1,982 ± 47 pg/mL/mg) and IL-1b (ND: 97 ± 12 HD: 133 ± 5 pg/mL/mg) without changing anti-inflammatory cytokine IL-10. Significance: Our study provides evidence that high-fat diet consumption leads to renal lipid accumulation, increases inflammatory cytokines, induces glomeruli retraction, and renal dysfunction. These damages observed in the kidney could be associated with an increased risk to advanced CKD in adulthood suggesting that reduction of high-fat ingestion during an early period of life can prevent metabolic disturbances and renal lipotoxicity.

Intra-Renal Angiotensin Levels Are Increased in High-Fructose Fed Rats in the Extracorporeal Renal Perfusion Model.

Overconsumption of fructose leads to metabolic syndrome as a result of hypertension, insulin resistance, and hyperlipidemia. In this study, the renal function of animals submitted to high fructose intake was analyzed from weaning to adulthood using in vivo and ex vivo methods, being compared with a normal control group. We investigated in ex vivo model of the role of the renin Angiotensin system (RAS) in the kidney. The use of perfused kidney from animals submitted to 8-week fructose treatment showed that high fructose intake caused metabolic and cardiovascular alterations that were consistent with other studies. Moreover, the isolated perfused kidneys obtained from rats under high fructose diet showed a 33% increase in renal perfusion pressure throughout the experimental period due to increased renal vascular resistance and a progressive fall in the glomerular filtration rate, which reached a maximum of 64% decrease. Analysis of RAS peptides in the high fructose group showed a threefold increase in the renal concentrations of angiotensin I (Ang I) and a twofold increase in angiotensin II (Ang II) levels, whereas no change in angiotensin 1-7 (Ang 1-7) was observed when compared with the control animals. We did not detect changes in angiotensin converting enzyme (ACE) activity in renal tissues, but there is a tendency to decrease. These observations suggest that there are alternative ways of producing Ang II in this model. Chymase the enzyme responsible for Ang II formation direct from Ang I was increased in renal tissues in the fructose group, confirming the alternative pathway for the formation of this peptide. Neprilysin (NEP) the Ang 1-7 forming showed a significant decrease in activity in the fructose vs. control group, and a tendency of reduction in ACE2 activity. Thus, these results suggest that the Ang 1-7 vasodilator peptide formation is impaired in this model contributing with the increase of blood pressure. In summary, rats fed high fructose affect renal RAS, which may contribute to several deleterious effects of fructose on the kidneys and consequently an increase in blood pressure.

Parallel evolution of vgsc mutations at domains IS6, IIS6 and IIIS6 in pyrethroid resistant Aedes aegypti from Mexico.

Aedes aegypti is the primary urban mosquito vector of viruses causing dengue, Zika and chikungunya fevers -for which vaccines and effective pharmaceuticals are still lacking. Current strategies to suppress arbovirus outbreaks include removal of larval-breeding sites and insecticide treatment of larval and adult populations. Insecticidal control of Ae. aegypti is challenging, due to a recent rapid global increase in knockdown-resistance (kdr) to pyrethroid insecticides. Widespread, heavy use of pyrethroid space-sprays has created an immense selection pressure for kdr, which is primarily under the control of the voltage-gated sodium channel gene (vgsc). To date, eleven replacements in vgsc have been discovered, published and shown to be associated with pyrethroid resistance to varying degrees. In Mexico, F1,534C and V1,016I have co-evolved in the last 16 years across Ae. aegypti populations. Recently, a novel replacement V410L was identified in Brazil and its effect on vgsc was confirmed by electrophysiology. Herein, we screened V410L in 25 Ae. aegypti historical collections from Mexico, the first heterozygote appeared in 2002 and frequencies have increased in the last 16 years alongside V1,016I and F1,534C. Knowledge of the specific vgsc replacements and their interaction to confer resistance is essential to predict and to develop strategies for resistance management.

Relationship between renal and cardiovascular changes in a murine model of glucose intolerance.

UNLABELLED: Nutrition is an important variable which may affect the risk for renal disease. We previously showed that a high fructose diet in mice produced hypertension and sympathetic activation [8]. The purpose of this study was to determine if a fructose diet altered renal function. A high fructose diet for 12 weeks impaired glucose tolerance, but caused no change in body weight, blood glucose or plasma insulin. Impairment in renal function was documented by the almost two fold increase in urinary protein excretion ( CONTROL: 6.6+/-0.6 vs. Fructose: 15.0+/-0.7 mmol protein/mmol creatinine; p<0.05) which was also accompanied by increases in urinary volume. The diet produced little change in renal histology, kidney weight or kidney weight/body weight ratio. Urinary excretion of angiotensin II/creatinine ( CONTROL: 78.9+/-16.6 vs. Fructose: 80.5+/-14.2 pg/mmol) and renal angiotensin converting enzyme activity ( CONTROL: 9.2+/-1.6 vs. Fructose: 7.6+/-1.0 ACE units) were not different between groups. There was a positive correlation between mean arterial pressure (r=0.7, p=0.01), blood pressure variability (BPV) (r=0.7, p=0.02), low frequency BPV component (r=0.677, p=0.03) and urinary protein excretion. Results show that consumption of a high fructose diet in mice had deleterious effects on renal function, which were correlated with cardiovascular changes.

Autonomic modulation of arterial pressure and heart rate variability in hypertensive diabetic rats.

OBJECTIVE: The aim of the present study was to evaluate the autonomic modulation of the cardiovascular system in streptozotocin (STZ)-induced diabetic spontaneously hypertensive rats (SHR), evaluating baroreflex sensitivity and arterial pressure and heart rate variability. METHODS: Male SHR were divided in control (SHR) and diabetic (SHR+DM, 5 days after STZ) groups. Arterial pressure (AP) and baroreflex sensitivity (evaluated by tachycardic and bradycardic responses to changes in AP) were monitored. Autoregressive spectral estimation was performed for systolic AP (SAP) and pulse interval (PI) with oscillatory components quantified as low (LF:0.2-0.6Hz) and high (HF:0.6-3.0Hz) frequency ranges. RESULTS: Mean AP and heart rate in SHR+DM (131+/-3 mmHg and 276+/-6 bpm) were lower than in SHR (160+/-7 mmHg and 330+/-8 bpm). Baroreflex bradycardia was lower in SHR+DM as compared to SHR (0.55+/-0.1 vs. 0.97+/-0.1 bpm/mmHg). Overall SAP variability in the time domain (standard deviation of beat-by-beat time series of SAP) was lower in SHR+DM (3.1+/-0.2 mmHg) than in SHR (5.7+/-0.6 mmHg). The standard deviation of the PI was similar between groups. Diabetes reduced the LF of SAP (3.3+/-0.8 vs. 28.7+/-7.6 mmHg2 in SHR), while HF of SAP were unchanged. The power of oscillatory components of PI did not differ between groups. CONCLUSIONS: These results show that the association of hypertension and diabetes causes an impairment of the peripheral cardiovascular sympathetic modulation that could be, at least in part, responsible for the reduction in AP levels. Moreover, this study demonstrates that diabetes might actually impair the reduced buffer function of the baroreceptors while reducing blood pressure.

Stress cardiovascular/autonomic interactions in mice.

Studies evaluated the role of the autonomic nervous system in the cardiovascular response to stress using radiotelemetric blood pressure (BP) recording coupled with autoregressive spectral analysis. Conscious male C57/BL6 mice with carotid arterial telemetric catheters were exposed to acute episodes of shaker stress before and after administration of cholinergic, beta1-adrenergic and alpha1-adrenergic receptor antagonists. Pulse interval (PI) and systolic arterial pressure (SAP) were analyzed for variance and the low frequency (LF: 0.1-1.0 Hz) and high frequency (HF: 1-5 Hz) spectral components. Stress (5 min) increased BP and heart rate (HR) as well as PI and SAP variability. PI variance increased from 41+/-6 to 75+/-14 ms2 while SAP variance increased from 25+/-5 to 55+/-9 mm Hg2. Autonomic blockade had specific effects on stress-induced changes in PI and SAP and their respective variability. Atropine reduced the tachycardia and abolished the increase in PI variance and its LF component. Data documents that in mice the cholinergic system is fundamental for the maintenance of HR variability. Atropine had no effects on the BP responses, either the increase in SAP or the variance associated with stress. Atenolol blocked the increase in PI and SAP variability induced by stress. Prazosin reduced the tachycardia produced by stress and blocked the increase in PI (only LF) and SAP variability. Using quantitative spectral analysis of telemetrically collected BP data in mice along with pharmacological antagonism, we were able to accurately determine the role of autonomic input in the mediation of the stress response. Data verify the role of sympathetic/parasympathetic balance in stress-induced changes in HR, BP and indices of variance.

Nocturnal hypertension in mice consuming a high fructose diet.

OBJECTIVE: To investigate the effect of fructose consumption on the light/dark pattern of blood pressure, heart rate and autonomic neural function in mice. BACKGROUND: Insulin resistant diabetes is associated with hypertension and autonomic dysfunction. There is evidence that the increasing incidence of diabetes may be related to dietary changes, including consumption of high levels of fructose. DESIGN/METHODS: C57/BL mice, instrumented with radiotelemetric arterial catheters, were fed a control or high fructose diet (60%). Cardiovascular parameters measured were light/dark pattern of mean arterial pressure (MAP), heart rate (HR) and variability (time and frequency domain). We also measured plasma insulin, glucose, lipids and angiotensin II (Ang II) as well as glucose tolerance. In situ hybridization was used to measure brainstem expression of tyrosine hydroxylase (TH) and Ang AT1a mRNA. RESULTS: Fructose diet (8 weeks) produced an increase in MAP, variance and low frequency domain (14+/-3 vs. 33+/-4 mm Hg(2), variance and 10+/-2 vs. 26+/-4 mm Hg(2), LF, control vs. fructose, P<0.01). The changes occurred only at night, a period of activity for mice. Glucose tolerance was attenuated in the fructose group. Fructose also increased plasma cholesterol (80+/-1 vs. 126+/-2 mg/dl, control vs. fructose, P<0.05) and plasma Ang II (18+/-5 vs.65+/-12 pg/ml, control vs. fructose, P<0.05). Depressor responses to alpha(1)-adrenergic blockade with prasozin were augmented in fructose-fed mice. Using quantitative in situ hybridization, we found that Ang AT1a receptor and TH mRNA expression were significantly increased in the brainstem locus coeruleus. CONCLUSION: A high fructose diet in mice produced nocturnal hypertension and autonomic imbalance which may be related to activation of sympathetic and angiotensin systems.

Exercise Training Prevents Cardiovascular Derangements Induced by Fructose Overload in Developing Rats.

The risks of chronic diseases associated with the increasing consumption of fructose-laden foods are amplified by the lack of regular physical activity and have become a serious public health issue worldwide. Moreover, childhood eating habits are strongly related to metabolic syndrome in adults. Thus, we aimed to investigate the preventive role of exercise training undertaken concurrently with a high fructose diet on cardiac function, hemodynamics, cardiovascular autonomic modulation and oxidative stress in male rats after weaning. Male Wistar rats were divided into 4 groups (n = 8/group): Sedentary control (SC), Trained control (TC), Sedentary Fructose (SF) and Trained Fructose (TF). Training was performed on a treadmill (8 weeks, 40-60% of maximum exercise test). Evaluations of cardiac function, hemodynamics, cardiovascular autonomic modulation and oxidative stress in plasma and in left ventricle (LV) were performed. Chronic fructose overload induced glucose intolerance and an increase in white adipose tissue (WAT) weight, in myocardial performance index (MPI) (SF:0.42±0.04 vs. SC:0.24±0.05) and in arterial pressure (SF:122±3 vs. SC:113±1 mmHg) associated with increased cardiac and vascular sympathetic modulation. Fructose also induced unfavorable changes in oxidative stress profile (plasmatic protein oxidation- SF:3.30±0.09 vs. SC:1.45±0.08 nmol/mg prot; and LV total antioxidant capacity (TRAP)- SF: 2.5±0.5 vs. SC:12.7±1.7 uM trolox). The TF group showed reduced WAT, glucose intolerance, MPI (0.35±0.04), arterial pressure (118±2mmHg), sympathetic modulation, plasmatic protein oxidation and increased TRAP when compared to SF group. Therefore, our findings indicate that cardiometabolic dysfunctions induced by fructose overload early in life may be prevented by moderate aerobic exercise training.

Acute and chronic stress influence blood pressure variability in mice.

There is evidence that alterations in heart rate and blood pressure variability (BPV) are associated with cardiovascular disease. We used a mice model to investigate the effects of acute and chronic stress on blood pressure variability (BPV) and heat rate variability (HRV). Shaker stress was given acutely (5 min, 150 cycles/min) and chronically (3 days, 2 min stress, 150 cycles/min, 45 sessions/day) in male C57BLJ mice. Systolic arterial pressure (SAP) and pulse interval (PI) time series were submitted to autoregressive spectral analysis with variability measured in the low-frequency (LF, 0.1-1.0 Hz) and high-frequency (HF, 1-5 Hz) ranges. In the acute experiment, MAP was increased significantly in the first 10 min poststress period (99+/-2 vs. 113+/-2 mm Hg) and returned to control levels 30 min poststress. HR was significantly higher in the initial poststress period (537+/-12 vs. 615+/-20 bpm). These alterations were associated with a marked increase in BPV (21+/-4 vs. 55+/-11 mm Hg2) and in power of LF oscillations (18+/-3 vs. 42+/-7 mm Hg2). On the other hand, chronic stress exposure produced a reduction in BPV (16+/-4 vs. 6+/-1 mm Hg2) and LF oscillations (11+/-3 vs. 3+/-1 mm Hg2). HRV was not altered after either acute or chronic stress. Spontaneous baroreflex sensitivity (SBS), determined by cross-spectral analysis between PI and BP, was reduced significantly in acute stress (-50%), but unchanged in chronic stress. Our results show that acute stress produced changes in BPV that may be associated with increased sympathetic activity and a reduction in blood pressure buffering. Under chronic conditions, there is no alteration in baroreflex sensitivity while BPV is reduced. This is likely related to the combination of sympathetic activation in the face of vasculature alterations.

Preventive role of exercise training in autonomic, hemodynamic, and metabolic parameters in rats under high risk of metabolic syndrome development.

High fructose consumption contributes to metabolic syndrome incidence, whereas exercise training promotes several beneficial adaptations. In this study, we demonstrated the preventive role of exercise training in the metabolic syndrome derangements in a rat model. Wistar rats receiving fructose overload in drinking water (100 g/l) were concomitantly trained on a treadmill (FT) or kept sedentary (F) for 10 wk. Control rats treated with normal water were also submitted to exercise training (CT) or sedentarism (C). Metabolic evaluations consisted of the Lee index and glycemia and insulin tolerance test (kITT). Blood pressure (BP) was directly measured, whereas heart rate (HR) and BP variabilities were evaluated in time and frequency domains. Renal sympathetic nerve activity was also recorded. F rats presented significant alterations compared with all the other groups in insulin resistance (in mg · dl(-1) · min(-1): F: 3.4 ± 0.2; C: 4.7 ± 0.2; CT: 5.0 ± 0.5 FT: 4.6 ± 0.4), mean BP (in mmHG: F: 117 ± 2; C: 100 ± 2; CT: 98 ± 2; FT: 105 ± 2), and Lee index (in g/mm: F = 0.31 ± 0.001; C = 0.29 ± 0.001; CT = 0.27 ± 0.002; FT = 0.28 ± 0.002), confirming the metabolic syndrome diagnosis. Exercise training blunted all these derangements. Additionally, FS group presented autonomic dysfunction in relation to the others, as seen by an ≈ 50% decrease in baroreflex sensitivity and 24% in HR variability, and increases in sympathovagal balance (140%) and in renal sympathetic nerve activity (45%). These impairments were not observed in FT group, as well as in C and CT. Correlation analysis showed that both Lee index and kITT were associated with vagal impairment caused by fructose. Therefore, exercise training plays a preventive role in both autonomic and hemodynamic alterations related to the excessive fructose consumption.

The effects of green tea consumption on cardiometabolic alterations induced by experimental diabetes.

We evaluated cardiac autonomic modulation by heart rate (HRV), and arterial pressure variability (APV), and metabolic response in streptozotocin diabetic rats treated with green tea. Male Wistar rats were separated in groups: control, drinking tap water (C), green tea-treated (GT) group, diabetic, drinking tap water (D), and diabetic, treated with green tea (DGT). Kidney mass was greater in D and DGT than in C and GT, but reduced in DGT compared to D. Green tea prevented the increase in creatinine clearance and reduced hyperglycemia in DGT compared to D. Arterial pressure was increased in GT and decreased in D compared to C. HRV was reduced in D compared with all groups. APV was decreased in D compared to C and recovery in DGT. Sympathetic modulation of APV was decreased in D compared with all groups. Green tea reduced hyperglycemia, prevented renal injury and autonomic dysfunction, suggesting reduced cardiovascular risk and target organ damage in diabetes.

Monosodium glutamate neonatal treatment induces cardiovascular autonomic function changes in rodents.

OBJECTIVES: The aim of this study was to evaluate cardiovascular autonomic function in a rodent obesity model induced by monosodium glutamate injections during the first seven days of life. METHOD: The animals were assigned to control (control, n = 10) and monosodium glutamate (monosodium glutamate, n = 13) groups. Thirty-three weeks after birth, arterial and venous catheters were implanted for arterial pressure measurements, drug administration, and blood sampling. Baroreflex sensitivity was evaluated according to the tachycardic and bradycardic responses induced by sodium nitroprusside and phenylephrine infusion, respectively. Sympathetic and vagal effects were determined by administering methylatropine and propranolol. RESULTS: Body weight, Lee index, and epididymal white adipose tissue values were higher in the monosodium glutamate group in comparison to the control group. The monosodium glutamate-treated rats displayed insulin resistance, as shown by a reduced glucose/insulin index (-62.5%), an increased area under the curve of total insulin secretion during glucose overload (39.3%), and basal hyperinsulinemia. The mean arterial pressure values were higher in the monosodium glutamate rats, whereas heart rate variability (>7 times), bradycardic responses (>4 times), and vagal (~38%) and sympathetic effects (~36%) were reduced as compared to the control group. CONCLUSION: Our results suggest that obesity induced by neonatal monosodium glutamate treatment impairs cardiac autonomic function and most likely contributes to increased arterial pressure and insulin resistance.

Exercise training prevents diastolic dysfunction induced by metabolic syndrome in rats.

OBJECTIVE: High fructose consumption contributes to the incidence of metabolic syndrome and, consequently, to cardiovascular outcomes. We investigated whether exercise training prevents high fructose diet-induced metabolic and cardiac morphofunctional alterations. METHODS: Wistar rats receiving fructose overload (F) in drinking water (100 g/l) were concomitantly trained on a treadmill (FT) for 10 weeks or kept sedentary. These rats were compared with a control group (C). Obesity was evaluated by the Lee index, and glycemia and insulin tolerance tests constituted the metabolic evaluation. Blood pressure was measured directly (Windaq, 2 kHz), and echocardiography was performed to determine left ventricular morphology and function. Statistical significance was determined by one-way ANOVA, with significance set at p<0.05. RESULTS: Fructose overload induced a metabolic syndrome state, as confirmed by insulin resistance (F: 3.6 ± 0.2 vs. C: 4.5 ± 0.2 mg/dl/min), hypertension (mean blood pressure, F: 118 ± 3 vs. C: 104 ± 4 mmHg) and obesity (F: 0.31 ± 0.001 vs. C: 0.29 ± 0.001 g/mm). Interestingly, fructose overload rats also exhibited diastolic dysfunction. Exercise training performed during the period of high fructose intake eliminated all of these derangements. The improvements in metabolic parameters were correlated with the maintenance of diastolic function. CONCLUSION: The role of exercise training in the prevention of metabolic and hemodynamic parameter alterations is of great importance in decreasing the cardiac morbidity and mortality related to metabolic syndrome.

Revisitando a fisiologia do sistema nervoso simpático: o que há de novo? / Facing sympathetic nervous system physiology: what's new?

o sistema nervoso autônomo (SNA), descrito no inicio do século passado, é definido como sendo o sistema de neurônios motores que inervam as glândulas e a musculatura lisa e cardíaca, sendo fundamental para a manutenção do equilibrio organismo, definindo esta situação com o termo "homeostasia", Atualmente, entretanto, reconhece-se que este sistema também apresenta neurônios sensoriais (neurônios aferentes), que transmitem as informações recebidas de receptores sensoriais autonômicos, principalmente viscerais, para o sistema nervoso central. O termo autônomo, hoje consagrado, vem da ideia de que este sistema atuava somente de forma autônoma; no entanto, hoje se admite que a atividade deste sistema é gerada, ou pelo menos supervisionada, pelo sistema nervoso central. A ativação e a desativação tônicas e reflexas de seus dois componentes, simpático e do parassimpático, determinam em condições fisiológicas ajustes do débito cardíaco e da resistência vascular periférica, contribuindo para a estabilização e manutenção da pressão arterial sistêmica durante diferentes situações fisiológicas, ampliando a capacidade de adaptação e sobrevivência do organismo. Neste contexto, o termo disautonomia se refere àquelas condições em que a função autonômica se modificou de maneira a contribuir negativamente para a saúde. Estas mudanças têm sido quantificadas e têm permitido estimar a contribuição da hiperatividade simpática na instalação e na manutenção da doença cardiovascular. Neste artigo, são revisados aspectos anatômicos e funcionais do sistema nervoso simpático e parassimpático, destacando os principais métodos de avaliação do SNA, bem como o papel da hiperatividade simpática como mecanismo desencadeador e de agravamento de disfunções cardiovasculares.

The autonomic nervous system (ANS) described at the beginning of the last century is defined as the system of motor neurons that innervate glands as well as smooth and cardiac musc/es essential for maintaining the body's balance, defining this situation with the term "homeostasis". Current1y, however it is recognized that this system also provides sensory neurons (afferent neurons) that transmit information received from sensory autonomic receptors mainly visceral to the central nervous system. The use of the term autonomic comes from the idea that this system acts only in autonomic way; however, nowadays it is accepted that the activity of this system is generated or at least supervised by the central nervous system. The tonic and reflex acti vation and deacti vation of both of its components, the sympathetic and the parasympathetic system, can determine adjustments in cardiac output and peripheral vascular resistance contributing to the stabilization and maintenance of systemic blood pressure during different physiological situations, expanding the capacity of adaptation and survival of the organismo ln this context, the terrn dysautonomia refers to those conditions in which autonomic function was changed in a way that negatively contribute to health. These changes have been quantified and have alJowed to estimate the contribution of sympathetic hyperactivity in the installation and maintenance of cardiovascular disease. In this manuscript anatomical and functional, sympathetic and parasympathetic nervous system aspects are reviewed, highJighting key evaluation methods of ANS and the role of sympathetic overacti vity as a trigger and as a worsening mechanism that can contribute to cardiovascular dysfunctions.

Genetic and dietary interactions: role of angiotensin AT1a receptors in response to a high-fructose diet.

The renin-angiotensin system (RAS) has been implicated in the cardiovascular complications of diabetes. We showed that a high-fructose diet increases blood pressure and plasma angiotensin and impairs glucose tolerance. We investigated the role of angiotensin AT(1a) receptors in the development of fructose-induced cardiovascular and metabolic dysfunction. Male angiotensin AT(1a) knockout (AT1aKO) and wild-type (AT1aWT) mice with arterial telemetric catheters were fed a standard diet or one containing 60% fructose. Fructose increased mean arterial pressure (MAP) in AT1aWT but only during the dark phase (8% increase). In AT1aKO mice, fructose unexpectedly decreased MAP, during both light and dark periods (24 and 13% decrease, respectively). Analytical methods were used to measure systolic arterial pressure (SAP) and pulse interval (PI) variability in time and frequency domains. In fructose-fed AT1aWT mice, there was an increase in SAP variance and its low-frequency (LF) domain (11 +/- 3 vs. 23 +/- 4 mmHg(2), variance, and 7 +/- 2 vs. 17 +/- 3 mmHg(2), LF, control vs. fructose, P < 0.004). There were no changes in SAP variance in AT1aKO mice. Depressor responses to alpha(1)-adrenergic blockade were augmented in fructose-fed AT1a WT compared with AT1aKO mice. Fructose inhibited glucose tolerance with a greater effect in AT1aWT mice. Fructose increased plasma cholesterol in both groups (P < 0.01) and reduced ANG II in AT1aKO mice. Results document prominent interactions between genetics and diet with data showing that in the absence of angiotensin AT(1a) receptors, a fructose diet decreased blood pressure.