Experimental Model Of Metabolic Syndrome Research Articles

Grape pomace and grape pomace extract improve insulin signaling in high-fat-fructose fed rat-induced metabolic syndrome.

In this study the effect of diet supplementation with grape pomace (GP) and grape pomace extract (GPE) on insulin sensitive tissues (adipose, liver and muscle) was evaluated in an experimental model of metabolic syndrome (MetS). MetS was developed by giving a high-fat-fructose (HFF) diet to Wistar rats. Six weeks of HFF diet induced weight gain, which was partially attenuated by GP (1 g per kg per day) and GPE (300 mg per kg per day) supplementation. HFF diet increased systolic blood pressure, triglycerides, insulin resistance (HOMA:IR) and inflammation (c-reactive protein (CRP)). Supplementation with GP prevented SBP, triglycerides and CRP increased and partially attenuated insulin resistance. On the other hand, GPE partially reduced SBP and triglycerides and significantly prevented insulin resistance and inflammation. Also, HFF diet induced higher triglycerides content and enhanced NADPH oxidase activity in the liver. Also, HFF diet increased the epididymal adipose tissue weight, enlarged adipocyte size, and c-jun N-terminal kinase (JNK) activation, probably contributing to a pro-inflammatory cytokine pattern (higher resistin) and lower adiponectin protein expression. These alterations may result in an impairment of insulin signaling cascade observed in adipose, liver and muscle tissue (IRS1, Akt, and extracellular signal-regulated kinases (ERK1/2)) from HFF rats. Supplementation with GP and to a greater extent GPE attenuated liver triglyceride content and adiposity and restored adipose, liver and muscle response to insulin. These findings show that supplementation with GP and GPE to a greater extent can counteract adiposity, inflammation, liver damage and impaired insulin signaling associated to MetS, supporting the utilization of winemaking residues in food industry/human health due to their high amount of bioactive compounds.

Effects of vitamin K on liver steatosis and pancreatic lipomatosis in experimental model of metabolic syndrome

Effects of vitamin K on liver steatosis and pancreatic lipomatosis in experimental model of metabolic syndrome

P-219: Effects of fish protein on brain lipid peroxidation and antioxidant enzymes in an experimental model of metabolic syndrome

Background The purpose of the present study was to investigate the protective effects of fish protein on brain glucose, lipid peroxidation and antioxidant enzymes in an experiment of metabolic syndrome. Methods Tweenty male Wistar rats were fed for 2 months sardine protein (S) or casein (C) with or without high fructose (HF) (64%). Changes in body weight, intake of food and water, and brain weight were measured. Brain glucose, TBARS, hydroperoxides, enzymatic antioxidants such as catalase (CAT) and glutathione peroxidase (GSH-Px) were also performed. Results Despite lower food and water intakes, the body mass index (BMI), body weight, absolute and relative brain weights and brain glucose were higher in fructose-fed rats than in controls rats. Moreover, an increase in hydroperoxides and a decrease in CAT and GSH Px were observed in rats on a high-fructose diet than in those on control diets. Administration of sardine protein for 60 days to HF rats resulted in significant attenuation of BMI, food intake, brain glucose and hydroperoxides and improved antioxidant enzyme activities in the brain as compared to casein-HF. Conclusions In conclusion, these results provide further evidence in support of the favorable effects of the sardine protein upon the metabolic disturbances prevailing in the fructose-induced metabolic syndrome

Morphological analysis of resveratrol influence on the state of neurons and glial cells in the neocortex in rats with metabolic syndrome.

Background. Investigation of metabolic mechanisms of cerebrovascular and cognitive disorders in patients with metabolic syndrome are still relevant. According to different data Resveratrol is a powerful antioxidant that improves insulin sensitivity, prevents decline in cognitive and mental functions, inhibits oxidative stress, etc. Objective. To identify morphological changes in the neocortex of rats with experimental fructose-induced metabolic syndrome in conditions of course administration of Resveratrol. Methods. The study included 24 white rats weighing 180-220 g. Rats were randomized into 3 experimental groups: I - intact rats (control), n = 8; II - animals with MS induced by 60% fructose solution during 8 weeks, n = 8; III - animals with MS that were treated with Resveratrol (20 mg/kg/day) for 14 days. At the end of the treatment the experimental animals were euthanized, and their brains were investigated histomorphologically. The histological sections were stained with methylene blue-Azure II for evaluation by light microscope. The number of neurons, glial cells, normal and apoptotic neurons were counted using the program ImageJ. Results. Light optical microscopy of the rat cerebral cortex in control group showed significant violations of cytoarchitectonics. The experimental course of metabolic syndrome has led to significant changes in neurons, glia and blood vessels of the neocortex. After treatment with Resveratrol the density of neurons increased moderately, percentage of hypochromic neurons and neuroglial index were decreased. However, the increase in the percentage of piknomorphic neurocytes and density of apoptotic and destructively altered neurocytes indicated low neuroprotective potential of Resveratrol and antioxidant therapy of metabolic syndrome in general. Conclusion. The experimental model of metabolic syndrome in rats leads to significant impairment of neuronal and glial apparatus of the neocortex. Our results showed that two weeks of daily Resveratrol treatment does not ensure sufficient protection of neurons and glia in conditions of experimental metabolic syndrome.

Experimental models of metabolic syndrome in rats

Metabolic syndrome (MS) is a disorder comprising central obesity, dyslipidemia, raised blood pressure, insulin resistance. The aim of the present study was to develop a cheap, easy and reproducible rat model of MS. 36 male Wistar rats were divided in 3 groups: a control group (C) receiving regular rat chow diet, a high-fat (HF) group receiving lard enriched rat chow and a high-fat high-fructose (HFHF) group receiving lard and fructose enriched rat chow. HF and HFHF groups had also 10% fructose in their drinking water. The duration of the study was 8 weeks. Body weights were measured weekly. At the end of the study insulin tolerance test (ITT) was performed. Liver and fat weight index were measured after sacrifice. Lipid biochemical parameters and insulin concentration in serum were determined. Liver triglycerides (TG) were measured. The oxidative stress in serum was assessed by thiobarbituric reactive substances (TBARS). At the end of the study the animals did not differ in their body weights across the groups, but the fat index in both HF and HFHF groups was higher. Plasma TG and cholesterol were raised in both groups and the ratio cholesterol/ HDL-cholesterol was higher. Liver TG were elevated in HFHF rats. ITT revealed reduced insulin sensitivity in both experimental groups although serum insulin was elevated only in HFHF group. TBARS were increased in both HF and HFHF groups. Both models displayed most of the features of MS; the HFHF probably better reflects the ‘cafeteria’ diet and its unhealthy consequences.

Acute administration of single oral dose of grape seed polyphenols restores blood pressure in a rat model of metabolic syndrome: role of nitric oxide and prostacyclin

The aims of this study were to evaluate the antihypertensive effectiveness of different doses of grape seed polyphenols in cafeteria diet-fed hypertensive rats (CHRs) and to establish the mechanism involved in the blood pressure (BP) lowering effect of these compounds in this experimental model of metabolic syndrome (MS). Male 8-week-old Wistar rats were fed cafeteria or standard (ST) diet for 10 weeks. After this, the antihypertensive effect of a single oral administration of a polyphenol grape seed extract (GSPE) was tested at different doses (250, 375 and 500 mg/kg) in CHRs. BP was recorded before and 2, 4, 6, 8, 24 and 48 h post-administration. The hypotensive effect of GSPE was also proved in ST diet-fed rats. Additionally, in other experiment, CHRs were orally administered 375 mg/kg GSPE. Four hours post-administration, the rats were intraperitoneally administrated 30 mg/kg NG-nitro-L-arginine methyl ester (L-NAME) or 5 mg/kg indomethacin [inhibitors of nitric oxide (NO) and prostacyclin synthesis, respectively]. BP was recorded initially and 6 h post-administration. GSPE produced a decrease in SBP and DBP, the most effective dose (375 mg/kg) showing an antihypertensive effect in CHRs similar to the drug captopril, and did not affect BP of ST diet-fed rats. The antihypertensive effect was completely abolished by L-NAME and partially inhibited by indomethacin. GSPE acts as an antihypertensive agent in a rat model of hypertension associated with MS. The change in endothelium-derived NO availability is one of the mechanisms involved in the antihypertensive effect of GSPE in CHRs. Additionally, endothelial prostacyclin contributes to the effect of GSPE on arterial BP.

Evaluation of Cardiac ACE in Rats with Experimental Model of Metabolic Syndrome Induced by Fructose Intake

The high consuming of fructose sugar is a concern for public health, since factors such as cardiovascular diseases, obesity, type‐2 diabetes and metabolic syndrome are related to this new food habits. The Renin‐Angiotensin System (RAS), an endocrine system responsible for regulating blood pressure, is widely studied since its components are sensitive to hyperglycemia and hyperinsulinemia, events that occur in the diet rich in fructose. The aim of the study was to evaluate an important marker of RAS, the angiotensin‐converting enzyme (ACE), in the heart of animals treated with fructose. Weaned Wistar rats were divided into control group (CG) and fructose group (FG, 10% in drinking water) and treated for 8 weeks. FG showed changes in lipid profile when compared to GC, with increased triglycerides (CG=39±3 vs FG=49±2*) and LDL (CG=48±2 vs FG=50±3*) and decreased HDL (CG=35±2 vs FG=24±1*). FG showed lower glucose tolerance than CG on GTT (CG=113±4 vs FG=169±2*), featuring the experimental model. Mean arterial pressure was increased in FG (CG=110±1 vs FG=125±1*)and quantification of ACE showed a significant increase in CG vs. FG (p<0.05), suggesting the increased activation of the RAS in GF than in GC, concluding that chronic ingestion of fructose may induce harmful and important metabolic changes that can lead to serious diseases, such as hypertension and type 2 diabetes. (*p<0,05 vs CG). Support by: PIBIC/Mackenzie

Exercise training prevents increased intraocular pressure and sympathetic vascular modulation in an experimental model of metabolic syndrome.

The present study aimed to study the effects of exercise training (ET) performed by rats on a 10-week high-fructose diet on metabolic, hemodynamic, and autonomic changes, as well as intraocular pressure (IOP). Male Wistar rats receiving fructose overload in drinking water (100 g/L) were concomitantly trained on a treadmill for 10 weeks (FT group) or kept sedentary (F group), and a control group (C) was kept in normal laboratory conditions. The metabolic evaluation comprised the Lee index, glycemia, and insulin tolerance test (KITT). Arterial pressure (AP) was measured directly, and systolic AP variability was performed to determine peripheral autonomic modulation. ET attenuated impaired metabolic parameters, AP, IOP, and ocular perfusion pressure (OPP) induced by fructose overload (FT vs F). The increase in peripheral sympathetic modulation in F rats, demonstrated by systolic AP variance and low frequency (LF) band (F: 37±2, 6.6±0.3 vs C: 26±3, 3.6±0.5 mmHg2), was prevented by ET (FT: 29±3, 3.4±0.7 mmHg2). Positive correlations were found between the LF band and right IOP (r=0.57, P=0.01) and left IOP (r=0.64, P=0.003). Negative correlations were noted between KITT values and right IOP (r=-0.55, P=0.01) and left IOP (r=-0.62, P=0.005). ET in rats effectively prevented metabolic abnormalities and AP and IOP increases promoted by a high-fructose diet. In addition, ocular benefits triggered by exercise training were associated with peripheral autonomic improvement.

The effects of wild blueberry consumption on plasma markers and gene expression related to glucose metabolism in the obese Zucker rat.

Impaired fasting blood glucose is one of the landmark signs of metabolic syndrome, together with hyperinsulinemia, dyslipidemia, hypertension, and a chronic proinflammatory, pro-oxidative, and prothrombotic environment. This study investigates the effect of wild blueberry (WB) consumption on blood glucose levels and other parameters involved in glucose metabolism in the obese Zucker rat (OZR), an experimental model of metabolic syndrome. Sixteen OZRs and 16 lean littermate controls (lean Zucker rat [LZR]) were fed an 8% enriched WB diet or a control (C) diet for 8 weeks. Plasma concentrations of glucose, insulin, glycated hemoglobin GHbA1c, resistin, and retinol-binding protein 4 (RBP4) were measured. Expression of the resistin, RBP4, and glucose transporter GLUT4 genes was also determined both in the liver and the abdominal adipose tissue (AAT). Plasma glycated hemoglobin HbA1c, RBP4, and resistin concentrations were significantly lower in OZRs following the WB diet (-20%, -22%, and -27%, respectively, compared to C diet, P<.05). Following WB consumption, resistin expression was significantly downregulated in the liver of both OZRs and LZRs (-28% and -61%, respectively, P<.05), while RBP4 expression was significantly downregulated in the AAT of both OZRs and LZRs (-87% and -43%, respectively, P<.05). All other markers were not significantly affected following WB consumption. In conclusion, WB consumption normalizes some markers related to glucose metabolism in the OZR model of metabolic syndrome, but has no effect on fasting blood glucose or insulin concentrations.

Effects of resveratrol treatment on the rat testis injury in an experimental model of metabolic syndrome

Metabolic syndrome (MS) triggers inflammation and oxidative stress which result in disfunction of crucial organs including testis (1). However, there are limited data about the histological and ultrastructural changes of testis after induction of MS. Therefore, this study was conducted to evaluate the rat testis morphology in a MS model and possible protective effects of resveratrol, an anti-inflammatory and anti-oxidant agent.

Physical exercise restores microvascular function in obese rats with metabolic syndrome.

Obesity and metabolic syndrome are related to systemic functional microvascular alterations, including a significant reduction in microvessel density. The aim of this study was to investigate the effects of exercise training on functional capillary density in the skeletal muscle and skin of obese rats with metabolic syndrome. We used male Wistar-Kyoto rats that had been fed a standard commercial diet (CON) or high-fat diet (HFD) for 32 weeks. Animals receiving the HFD were randomly divided into sedentary (HFD+SED) and training groups (HFD+TR) at the 20(th) week. After 12 weeks of aerobic treadmill training, the maximal oxygen uptake (VO2max); hemodynamic, biochemical, and anthropometric parameters; and functional capillary density were assessed. In addition, a maximal exercise test was performed. Exercise training increased the VO2max (69 ± 3 mL/kg per min) and exercise tolerance (30 ± 1 min) compared with the HFD+SED (41 ± 6 mL/kg per min, P < 0.05 and 16 ± 1 min, P < 0.001) and with the CON (52 ± 7 mL/kg per min and 18 ± 1 min, P < 0.05) groups. The HFD+TR group also showed reduced retroperitoneal fat (0.03 ± 0.00 vs. 0.05 ± 0.00 gram/gram, P < 0.001), epididymal fat (0.01 ± 0.00 vs. 0.02 ± 0.00 gram/gram, P < 0.001), and systolic blood pressure (127 ± 2 vs. 150 ± 2 mmHg, P<0.001). The HFD+TR group also demonstrated improved glucose tolerance, as evaluated by an intraperitoneal glucose tolerance test, fasting plasma glucose levels (5.0 ± 0.1 vs. 6.4 ± 0.2 mmol/L, P<0.001) and fasting plasma insulin levels (26.5 ± 2.3 vs. 38.9 ± 3.7 μIU/mL, P < 0.05). Glucose tolerance did not differ between HFD+TR and CON groups. Exercise training also increased the number of spontaneously perfused capillaries in the skeletal muscle (252 ± 9 vs. 207 ± 9 capillaries/mm(2)) of the training group compared with that in the sedentary animals (260 ± 15 capillaries/mm(2)). These results demonstrate that exercise training reverses capillary rarefaction in our experimental model of metabolic syndrome and obesity.

Combined exercise training improves cardiovascular and inflammatory parameters in an experimental model of metabolic syndrome and menopause (706.12)

The aim of this study was to verify the effects of combined exercise training (aerobic+resistance) in an experimental model of metabolic syndrome and menopause on cardiovascular autonomic modulation and inflammation. Female SHR rats were divided into (n=8/group): hypertensive (H), hypertensive ovariectomized (HO) and hypertensive ovariectomized submitted to fructose overload sedentary (100g/L in drinking water) (FHO) or trained (FHOT). Combined exercise training was performed in ladder+treadmill on alternate days (5x/week, 8 weeks, 40‐60% maximal exercise test). Arterial pressure (AP) signals were directly recorded. Cardiovascular autonomic modulation was evaluated by spectral analysis. Cardiac levels of TNFα and IL‐10 were measured by Elisa. AP was higher in FHO group (174±4 vs. H: 146±4 HO: 164±5 mmHg) and combined exercise training attenuated this dysfunction (FHOT: 158±4 mmHg). FHOT group showed resting bradycardia. The vascular sympathetic modulation (LF‐IP) was higher in FHO group (10.62±2.33 mmHg2) and exercise training normalized this change (4.51±0.32 vs. H: 5.06±0.91; HO: 5.07±0.52 mmHg2). The TNFα was higher in FHO group than H and HO groups and exercise training reduced this parameter. Negative correlation was observed between adiposity tissue and IL‐10 among sedentary groups (r=‐0.6, p&lt;0.05). In conclusion, fructose overload induced impairment in cardiovascular autonomic control and in inflammatory parameters in hypertensive rats undergoing ovarian hormones deprivation. The combined exercise training reverted and/or attenuated these impairments.Grant Funding Source: FAPESP 2011/15828‐9

Structural and functional microvascular alterations in a rat model of metabolic syndrome induced by a high‐fat diet

To investigate microvascular alterations in an experimental model of metabolic syndrome induced by a high-fat diet (HFD) associated with salt supplementation (0.5% NaCl). Wistar Kyoto rats were fed standard chow (control group, CONT) or HFD for 20 weeks. The functional capillary density (FCD) was assessed using intravital fluorescence videomicroscopy. The HFD group presented a higher systolic blood pressure, plasma glucose and insulin levels, total and LDL-cholesterol levels, triglycerides, and visceral and epididymal fat when compared with the CONT group. When compared with the CONT group, the HFD group showed a lower FCD in the skeletal muscle (P < 0.05) but not in the skin (P > 0.05). The HFD group also had a lower capillary-to-fiber ratio in the skeletal muscle (P < 0.01). The capillary volume density-to-fiber volume density ratio in the left ventricle of the HFD was also reduced (P < 0.01). Finally, rats fed with HFD showed ventricular hypertrophy and increased cardiomyocyte diameter (P < 0.01). The long-term administration of a HFD associated with salt supplementation to rats generates an experimental model of metabolic syndrome characterized by central body fat deposition, insulin resistance, glucose intolerance, hypertriglyceridemia, hypercholesterolemia, arterial hypertension, cardiac remodeling, and rarefaction of the microcirculation in the heart and skeletal muscle.

Role of Cox-2 in Vascular Inflammation: An Experimental Model of Metabolic Syndrome

The objective of this work was to demonstrate the role of COX-2 enzyme at the vascular in experimental model of metabolic syndrome. SHR male WKY rats were employed; they were distributed in 8 groups (n = 8 each): control (W); W + L: WKY rats receiving 20 mg/kg of lumiracoxib by intraesophageal administration; SHR; SHR + L: SHR + 20 mg/kg of lumiracoxib by intraesophageal administration; Fructose-Fed Rats (FFR): WKY rats receiving 10% (w/v) fructose solution in drinking water during all 12 weeks; FFR + L: FFR + 20 mg/kg of lumiracoxib by intraesophageal administration; Fructose-Fed Hypertensive Rats (FFHR): SHR receiving 10% (w/v) fructose solution in drinking water during all 12 weeks; and FFHR + L: FFHR + 20 mg/kg of lumiracoxib by intraesophageal administration. Metabolic variables, blood pressure, morphometric variables, and oxidative stress variables were evaluated; also MMP-2 and MMP-9 (collagenases), VCAM-1, and NF-κB by Westernblot or IFI were evaluated. FFHR presented all variables of metabolic syndrome; there was also an increase in oxidative stress variables; vascular remodeling and left ventricular hypertrophy were evidenced along with a significant increase in the expression of the mentioned proinflammatory molecules and increased activity and expression of collagenase. Lumiracoxib was able to reverse vascular remodeling changes and inflammation, demonstrating the involvement of COX-2 in the pathophysiology of vascular remodeling in this experimental model.

Role of Renin-Angiotensin System and Oxidative Stress on Vascular Inflammation in Insulin Resistence Model

(1) This study aims to demonstrate the causal involvement of renin angiotensin system (RAS) and oxidative stress (OS) on vascular inflammation in an experimental model of metabolic syndrome (MS) achieved by fructose administration to spontaneously hypertensive rats (FFHR) during 12 weeks. (2) Chronic treatment with candesartan (C) (10 mg/kg per day for the last 6 weeks) or 4OH-Tempol (T) (10−3 mmol/L in drinking water for the last 6 weeks) reversed the increment in metabolic variables and systolic blood pressure. In addition, chronic C treatment reverted cardiovascular remodeling but not T. (3) Furthermore, chronic treatment with C was able to completely reverse the expression of NF-κB and VCAM-1, but T only reduced the expression. C reduced the expression of proatherogenic cytokines as CINC2, CINC3, VEGF, Leptin, TNF-alpha, and MCP-1 and also significantly reduced MIP-3, beta-NGF, and INF-gamma in vascular tissue in this experimental model. T was not able to substantially modify the expression of these cytokines. (4) The data suggest the involvement of RAS in the expression of inflammatory proteins at different vascular levels, allowing the creation of a microenvironment suitable for the creation, perpetuation, growth, and destabilization of vascular injury.

Hypertension and Cardiometabolic Risk Factors

Hypertension and Cardiometabolic Risk Factors

Melatonin ameliorates low‐grade inflammation and oxidative stress in young Zucker diabetic fatty rats

The aim of this study was to investigate the effects of melatonin on low-grade inflammation and oxidative stress in young male Zucker diabetic fatty (ZDF) rats, an experimental model of metabolic syndrome and type 2 diabetes mellitus (T2DM). ZDF rats (n = 30) and lean littermates (ZL) (n = 30) were used. At 6 wk of age, both lean and fatty animals were subdivided into three groups, each composed of 10 rats: naive (N), vehicle treated (V), and melatonin treated (M) (10 mg/kg/day) for 6 wk. Vehicle and melatonin were added to the drinking water. Pro-inflammatory state was evaluated by plasma levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP). Also, oxidative stress was assessed by plasma lipid peroxidation (LPO), both basal and after Fe(2+)/H2O2 inducement. ZDF rats exhibited higher levels of IL-6 (112.4 ± 1.5 pg/mL), TNF-α (11.0 ± 0.1 pg/mL) and CRP (828 ± 16.0 µg/mL) compared with lean rats (IL-6, 89.9 ± 1.0, P < 0.01; TNF-α, 9.7 ± 0.4, P < 0.01; CRP, 508 ± 21.5, P < 0.001). Melatonin lowered IL-6 (10%, P < 0.05), TNF-α (10%, P < 0.05), and CRP (21%, P < 0.01). Basal and Fe(2+)/H2O2-induced LPO, expressed as malondialdehyde equivalents (µmol/L), were higher in ZDF rats (basal, 3.2 ± 0.1 versus 2.5 ± 0.1 in ZL, P < 0.01; Fe(2+)/H2O2-induced, 8.7 ± 0.2 versus 5.5 ± 0.3 in ZL; P < 0.001). Melatonin improved basal LPO (15%, P < 0.05) in ZDF rats, and Fe(2+)/H2O2- induced LPO in both ZL (15.2%, P < 0.01) and ZDF rats (39%, P < 0.001). These results demonstrated that oral melatonin administration ameliorates the pro-inflammatory state and oxidative stress, which underlie the development of insulin resistance and their consequences, metabolic syndrome, diabetes, and cardiovascular disease.

Neuropeptide Y improves myocardial perfusion and function in a swine model of hypercholesterolemia and chronic myocardial ischemia

Pharmacologically induced angiogenesis could be a promising option in clinical situations with diffuse inoperable coronary artery disease e.g. metabolic syndrome and diabetes mellitus. The failure of focused cytokine, stem cell and gene therapies to achieve both perfusion and functional improvement in clinical trials suggests a more centralized control mechanism. Neuropeptide-Y (NPY) is one such natural neurotransmitter that is known to exert a multifaceted role during neo-angiogenesis and can possibly act as the central control. To date, the ability to harness the ‘master switch’ nature of NPY in a specific experimental model of metabolic syndrome and chronic myocardial ischemia has not been conclusively demonstrated. We hypothesized that infiltration of NPY into an area of chronic ischemia in a metabolic syndrome swine model would induce angiogenesis and improve myocardial perfusion and function. An osmotic pump was inserted three weeks after surgical induction of focal myocardial ischemia. We delivered either NPY or placebo for five weeks, after which the myocardial tissue was harvested for analysis. Assessments of myocardial perfusion and function were performed at each stage of the experiment. Local infiltration of NPY significantly improved collateral vessel formation, blood flow and myocardial function. We believe activation of NPY receptors may be a potential target therapy for patients with diffuse coronary artery disease.

Cardiometabolic benefits of exercise training in an experimental model of metabolic syndrome and menopause

The aim of this study was to investigate the cardiometabolic effects of exercise training in ovariectomized hypertensive rats both submitted and not submitted to fructose overload. Spontaneously hypertensive ovariectomized rats were divided into sedentary and trained (THO) groups submitted to normal chow and sedentary and trained groups submitted to fructose overload (100 g/L in drinking water for 19 wk). Exercise training was performed on a treadmill (8 wk). Arterial pressure (AP) was directly recorded. Cardiovascular autonomic control was evaluated through pharmacological blockade (atropine and propranolol) and in the time and frequency domains by spectral analysis. The THO group presented reduced AP (approximately 16 mm Hg) and enhanced cardiac vagal tonus (approximately 49%) and baroreflex sensitivity (approximately 43%) compared with the sedentary hypertensive ovariectomized group. Exercise training attenuated metabolic impairment, resting tachycardia, cardiac and vascular sympathetic increases, and baroreflex sensitivity decrease induced by fructose overload in hypertensive rats. However, the trained hypertensive ovariectomized group submitted to fructose overload presented higher AP (approximately 32 mm Hg), associated with baroreflex sensitivity (approximately 69%) and parasympathetic dysfunctions compared with the THO group. These data suggest that the metabolic disorders in hypertensive rats after ovarian hormone deprivation could blunt and/or attenuate some exercise training benefits.

Dissociation of antihypertensive and metabolic response to losartan and spironolactone in experimental rats with metabolic sindrome

The treatment of arterial hypertension (AH) in patients with metabolic syndrome (MS) is a challenge, since non drug therapies are difficult to implement and optimal pharmacological treatment is not fully established. To assess the blockade of the rennin angiotensin aldosterone system (RAAS) in blood pressure (BP) in renal function and morphology in an experimental model of MS induced by high fat diet. Wistar rats were fed on high fat diet from the fourth week of life, for 20 weeks. The groups received Losartan or Spironolactone from the eighth week of life. We weekly evaluated the body weight and BP by tail plethysmography. At the end of the experiment oral glucose tolerance, lipid profile, creatinine clearance tests, and the direct measurement of BP were performed. A morphometric kidney analysis was performed. The administration of high-fat diet was associated with the development of MS, characterized by central fat accumulation, hypertension, hyperglycemia and hypertriglyceridemia. In this model there were no changes in renal histomorphometry. The blockade of angiotensin II (Ang II) receptor AT1 prevented the development of hypertension. The mineralocorticoid blockage did not have antihypertensive efficacy but was associated with reduction of abdominal fat. The dissociation of the antihypertensive response to the blockades of Ang II receptors and mineralocorticoid indicates the involvement of Ang II in the pathogenesis of hypertension associated with obesity. Reduction of central obesity with Spironolactone suggests the presence of mineralocorticoid adipogenic effect.