Antihypertensive treatment of end-stage renal disease patients on hemodialysis does not alter circulating ACE and ACE2 activity and angiotensin peptides.

Cardiovascular diseases (CVD) are the main causes of death in hemodialysis patients, representing a public health challenge. We investigated the effect of different antihypertensive treatments on circulating levels of renin-angiotensin system (RAS) components in end-stage renal disease (ESRD) patients on hemodialysis. ESRD patients were grouped following the prescribed antihypertensive drugs: ß-blocker, ß-blocker+ACEi and ß-blocker+AT1R blocker. ESDR patients under no antihypertensive drug treatment were used as controls. Blood samples were collected before hemodialysis sessions. Enzymatic activities of the angiotensin-converting enzymes ACE and ACE2 were measured through fluorescence assays and plasma concentrations of the peptides Angiotensin II (Ang II) and Angiotensin-(1-7) [Ang-(1-7)] were quantified using mass spectrometry (LC-MS/MS). ACE activity was decreased only in the ß-blocker+ACEi group compared to the ß-blocker+AT1R, while ACE2 activity did not change according to the antihypertensive treatment. Both Ang II and Ang-(1-7) levels also did not change according to the antihypertensive treatment. We concluded that the treatment of ESRD patients on hemodialysis with different antihypertensive drugs do not alter the circulating levels of RAS components.

Ellagic Acid prevents vascular dysfunction in small mesenteric arteries of ovariectomized hypertensive rats.

Cardiovascular diseases rank the top causes of death worldwide, with a substantial increase in women compared to men. Such increase can beexplained by the drastic decrease in 17-ß-estradiol hormone during menopause and associated with endothelium-dependent vascular dysfunction. The current treatments for cardiovascular diseases (e.g., hypertension), are only palliative and therefore, feasible, non-invasive options for preventing further vascular damage are needed. The polyphenol ellagic acid (EA) has risen as a candidate with possible vascular protection properties. This study evaluated the effects of EA in small mesenteric arteries of ovariectomized spontaneously hypertensive rats. Our findings showed that EA oral treatment for 4 weeks preserved vasodilation endothelial-dependent in acetylcholine pre-constricted arteries of spontaneously hypertensive rats to the same extent as 17-ß-estradiol treatment, an effect that was abolished in the presence of the nitric oxide synthase inhibitor L-NitroG-L-Arginine Methyl Ester. Moreover, EA induced vascular nitric oxide release, by increasing both the activitation site phosphorylation and total levels of the endothelial nitric oxide synthase. Finally, EA decreased superoxide anion while increased total levels of the antioxidant enzymes Superoxide Dismutase 2 and catalase. We concluded that EA has vasodilation properties acting via endothelial nitric oxide synthase activation and a potential antioxidant effect by stimulating the Superoxide Dismutase 2-catalase pathway.

Ellagic acid prevents myocardial infarction-induced left ventricular diastolic dysfunction in ovariectomized rats.

Estrogen deficiency is associated with increased oxidative stress, which can contribute to left ventricular diastolic dysfunction (LVDD). We hypothesized that oral treatment with ellagic acid (EA), a potent and natural antioxidant compound, can improve MI-induced LVDD in ovariectomized rats, by reducing the formation of reactive oxygen species. Ovariectomized rats MI-induced LVDD followed by treatment with vehicle (DD) or EA (DD + EA) for 4 weeks. Non-LVDD-induced rats treated with vehicle (S) or EA (S + EA) were used as controls. Left ventricular systolic pressure; left ventricular end-diastolic pressure (LVEDP); maximum rate of pressure rise: +dP/dt and fall: -dP/dt) were evaluated in all animals after treatment. Left ventricle superoxide anion formation was quantified in situ by fluorescence. Phospho-CAMKII, SOD2, catalase, and gp91-phox abundances were evaluated by Western blot analyses. SOD (superoxide dismutase) and catalase activities were measured by spectrophotometry. The results showed that the LVEDP was significantly increased in both DD and DD + EA groups compared to S and S + EA. However, LVEDP in the DD + EA group was significantly decreased compared to DD, indicating an EA-mediated effect. In the DD group, superoxide production and gp91-phox protein abundance were increased while SOD2 abundance was decreased when compared to the S and S + EA groups. An increase in SOD activity was also observed in the DD + EA group. EA treatment reduced CaMKII phosphorylation in the DD + EA group compared to the DD. We concluded that EA treatment attenuated diastolic dysfunction in our experimental model, via reduction of reactive oxygen species and CaMKII activity, indicating EA as a promising natural therapeutic option for cardiac dysfunction.

Role of the renin-angiotensin system in the nandrolone-decanoate-induced attenuation of the Bezold-Jarisch reflex.

The androgen nandrolone decanoate (ND) is known to cause cardiovascular abnormalities, such as attenuation of the Bezold-Jarisch Reflex (BJR), cardiac hypertrophy, and elevation of mean arterial pressure (MAP). Futhermore, a relationship between androgens and the renin-angiotensin system (RAS) has been reported. The purpose of this study was to evaluate the influence of RAS on the BJR, cardiac and prostatic hypertrophy, and MAP evoked by ND. For this, male Wistar rats were treated with ND (10 mg·(kg body mass)(-1) for 8 weeks; DECA), or vehicle (control animals; CON), or enalapril (10 mg·(kg body mass)(-1), daily; CONE), or ND and enalapril (10 mg ND + 10 mg enalapril per kilogram of body mass; DECAE). After 8 weeks of treatment, the BJR was evaluated by bradycardia and hypotensive responses that were elicited by serotonin administration (2-32 µg·(kg body mass)(-1)). MAP was assessed; cardiac and prostate hypertrophy were determined by the ratio of the tissue mass:body mass, and by histological analysis of the heart. Animals from the DECA group showed prostatic and cardiac hypertrophy, elevation in mean arterial pressure, and an impairment of BJR. Co-treatment with enalapril inhibited these changes. The data from the present study suggest that RAS has an impact on BJR attenuation, cardiac and prostatic hypertrophy, and the elevation in MAP evoked by ND.

Long-term treatment with supraphysiological doses of nandrolone decanoate reduces the sensitivity of Bezold-Jarisch reflex control of heart rate and blood pressure.

We investigated the influence of long-term treatment with supraphysiological doses of an anabolic-androgenic steroid on the Bezold-Jarisch reflex (BJR) control of heart rate (HR) and diastolic arterial pressure (DAP), and whether this treatment induced cardiac hypertrophy. Male rats were treated with nandrolone decanoate (ND) (10 mg kg(-1) body weight for 8 weeks; DECA) or vehicle (control animals; CON). After 8 weeks of treatment, the BJR was evaluated by bradycardia and hypotension responses that were elicited by serotonin administration (2-32 microg kg(-1)). Mean arterial pressure (MAP) was assessed and cardiac hypertrophy was determined by the ratio of the left and right ventricle weight/body weight (LVW/BW and RVW/BW, respectively) and by histological analysis. Total body protein (TBP) content was also evaluated. Nandrolone decanoate treatment increased MAP (CON=99+/- 1 mmHg; DECA=109+/-2 mmHg; p<0.01) but did not change the mean basal HR (CON=356+/-13 bpm; DECA=367+/-11 bpm). The treatment also induced LV and RV hypertrophy (LVW/BW: CON=1.86+/-0.04 mg g(-1), DECA=2.17+/-0.04 mg g(-1), p<0.01; RVW/BW: CON=0.42+/-0.02 mg g(-1), DECA=0.53+/-0.03 mg g(-1), p<0.05) and reduced the number of myocyte nuclei/high-power field (CON=23.0+/-2; DECA=9.4+/-1.0; p<0.01). ND treatment blunted the HR and DAP decreases induced by serotonin. ND determines an increase in the TBP content in DECA group (35+/-3%; p<0.01) compared with control animals (18+/-1%). We conclude that 8 weeks of ND treatment induces anabolic effect, cardiac hypertrophy and an elevation of MAP. This treatment also reduces the sensitivity of the BJR control of bradycardia and blood pressure, possibly due to cardiac hypertrophy. The blunted BJR response could contribute to the MAP elevation in DECA animals.

Ultrasound lipoclasia on subcutaneous adipose tissue to produce acute hyperglycemia and enhance acute inflammatory response in healthy female rats.

BACKGROUND: Ultrasound lipoclasia (USL) on white adipose tissue (WAT) has been largely used in the treatment of cellulite. Nevertheless, the acute consequences of this therapy on metabolism and biochemical profile are significant and should be taken into account. OBJECTIVES: To analyze the acute metabolic effects of USL in WAT of healthy rats using analyses of body composition, biochemical profile, and inflammatory markers. METHODS: Female Wistar rats weighing approximately 250 g were divided into two groups (n=10 each): control and treated. The treated group was submitted to USL, a single 3-MHz ultrasound application (5.6 W/cm(2)), in gluteal-femoral WAT (3 cm(2)) for 3 minutes. Animals were subjected to glycemic control. Body composition was analyzed using bio-impedance, and lipid profile, insulinemia, C-reactive protein (CRP), and lactate dehydrogenase (LDH) were measured. RESULTS: USL reduced (p<.05) body fat mass. The basal metabolic rate was found to have increased (p<.05). Basal insulin and the lipoprotein profile were not different, although the glycemic curve and CRP and LDH (p<.05) levels were higher. CONCLUSIONS: Fat mobilization using USL provokes acute hyperglycemia and enhances an acute inflammatory response, producing cardiometabolic risk in female rats.

Exercise training improves vascular reactivity in ovariectomized rats subjected to myocardial infarction.

The aim of this study was to evaluate the effects of exercise training (ET) on the aortic vascular reactivity of ovariectomized and infarcted rats. The animals were divided into 5 groups: Control, Ovariectomized + SHAM sedentary (OVX+SHAMSED), OVX+SHAM and ET (OVX+SHAMET), OVX + Myocardial Infarction sedentary (OVX+MISED), and OVX + MI and ET (OVX+MIET). ET protocol (60 minutes/day, 5x/week) in a motorized treadmill began 15 days after MI and lasted 8 weeks. The endothelium-dependent and endothelium-independent vascular reactivity were evaluated as well as the role of the reactive oxygen species (ROS). Superoxide and nitric oxide (NO) production were analyzed in situ using DHE and DAF-2 fluorescence, respectively. The expression of gp91phox and of the antioxidant enzymes were evaluated by western blotting in the thoracic aorta samples. MI promoted a significant increase in the contractile response and impaired endothelium-mediated relaxation. However, ET prevented the impairment in the vascular reactivity in MI animals. In addition, the protein expression of gp91phox and superoxide production increased and the NO production decreased in the OVX+MISED group but not in the OVX+MIET group. Therefore, ET improves vascular reactivity in MI ovariectomized rats by preventing the increase in the expression of gp91phox and the decrease in the antioxidant enzymes, resulting in a normal ROS and NO production. Thus, ET can be an effective therapeutic strategy for improving the MI-induced vascular alterations in estrogen deficiency condition.

Estrogen Therapy Worsens Cardiac Function and Remodeling and Reverses the Effects of Exercise Training After Myocardial Infarction in Ovariectomized Female Rats.

There is an increase in the incidence of cardiovascular events such as myocardial infarction (MI) after menopause. However, the use of estrogen therapy (E2) remains controversial. The aim of this study was to evaluate the effects of E2, alone and combined with exercise training (ET), on cardiac function and remodeling in ovariectomized (OVX) rats after MI. Wistar female rats underwent ovariectomy, followed by MI induction were separated into five groups: S; MI; MI+ET; MI+E2; and MI+ET+E2. Fifteen days after MI or sham surgery, treadmill ET and/or estrogen therapy [17-ß estradiol-3-benzoate (E2), s.c. three times/week] were initiated and maintained for 8 weeks. After the treatment and/or training period, the animals underwent cardiac hemodynamic evaluation through catheterization of the left ventricle (LV); the LV systolic and diastolic pressures (LVSP and LVEDP, respectively), maximum LV contraction and relaxation derivatives (dP/dt+ and dP/dt-), and isovolumic relaxation time (Tau) were assessed. Moreover, histological analyses of the heart (collagen and hypertrophy), cardiac oxidative stress [advanced oxidation protein products (AOPPs)], pro- and antioxidant protein expression by Western blotting and antioxidant enzyme activity in the heart were evaluated. The MI reduced the LVSP, dP/dt+ and dP/dt- but increased the LVEDP and Tau. E2 did not prevent the MI-induced changes in cardiac function, even when combined with ET. An increase in the dP/dt+ was observed in the E2 group compared with the MI group. There were no changes in collagen deposition and myocyte hypertrophy caused by the treatments. The increases in AOPP, gp91-phox, and angiotensin II type 1 receptor expression induced by MI were not reduced by E2. There were no changes in the expression of catalase caused by MI or by the treatments, although, a reduction in superoxide dismutase (SOD) expression occurred in the groups subjected to E2 treatment. Whereas there were post-MI reductions in activities of SOD and catalase enzymes, only that of SOD was prevented by ET. Therefore, we conclude that E2 therapy does not prevent the MI-induced changes in cardiac function and worsens parameters related to cardiac remodeling. Moreover, E2 reverses the positive effects of ET when used in combination, in OVX infarcted female rats.

Effects of treatment with chemotherapy and/or tamoxifen on the biomarkers of cardiac injury and oxidative stress in women with breast cancer.

There has been an increase in deaths from cardiovascular diseases following breast cancer therapy. Evidence has shown that this outcome is, in part, associated with cardiotoxicity induced by the chemotherapeutic drugs and the increase in oxidative stress. The aim of this study was to evaluate the effects of chemotherapy and hormone therapy with tamoxifen on the biomarkers of cardiac injury and oxidative stress in women with breast cancer.Thirty women were followed-up for 1 year and were divided into 3 groups according to the treatment protocol: women treated only with tamoxifen and clinical follow up for 12 months (Tam, n = 10); women treated only with chemotherapy for 6 months with clinical follow up for an additional 6-month period (Chemo, n = 10); and women who received chemotherapy for 6 months followed by a 6-month period only with tamoxifen therapy and clinical follow up (Chemo + Tam, n = 10). Analysis of the blood levels of cardiac troponin I (cTnI), advanced oxidation protein products (AOPP) and the activity of the plasmatic isoform of the antioxidant enzyme glutathione peroxidase (GPx) was performed before treatment (T0) and at 6 (T6) and 12 (T12) months after treatment.The Chemo group showed higher levels of cTnI (0.065 ±â€Š0.006 ng/mL, P < .05) and AOPP (4.99 ±â€Š0.84 µmol/L, P < .05) and reduced GPx activity (24.4 ±â€Š1.1 nM/min/mL, P < .05) at T12 than the Tam group (cTnI: 0.031 ±â€Š0.001 ng/mL; AOPP: 1.40 ±â€Š0.10 µmol/L; GPx: 28.0 ±â€Š0.7 nM/min/mL) and Chemo + Tam group (cTnI: 0.037 ±â€Š0.002 ng/mL; AOPP: 2.53 ±â€Š0.30 µmol/L; GPx: 29.5 ±â€Š1.0 nM/min/mL).These data support the hypothesis that long-term oxidative stress after chemotherapy may have an impact on cardiovascular diseases and that tamoxifen has cardioprotective effects.

Changes in retinal microvascular diameter in patients with diabetes.

BACKGROUND AND OBJECTIVES: Diabetic retinopathy is the main microvascular complication in diabetes mellitus and needs to be diagnosed early to prevent severe sight-threatening retinopathy. The purpose of this study was to quantify the retinal microvasculature pattern and analyze the influence of blood glucose level and the duration of diabetes mellitus on the retinal microvasculature. METHODS: Two groups were analyzed: patients with diabetes (N=26) and patients without diabetes, ie, controls (N=26). A quantitative semiautomated method analyzed retinal microvasculature. The diameters of arterioles and venules were measured. The total numbers of arterioles and venules were counted. The ratio of arteriole diameter to venule diameter was calculated. The retinal microvasculature pattern was related to clinical and biochemical parameters. RESULTS: Patients with diabetes exhibited larger venule diameters in the upper temporal quadrant of the retina compared to the lower temporal quadrant (124.85±38.03 µm vs 102.92±15.69 µm; P<0.01). Patients with diabetes for 5 or more years had larger venule diameters in the upper temporal quadrant than patients without diabetes (141.62±44.44 vs 112.58±32.11 µm; P<0.05). The degree of venodilation in the upper temporal quadrant was positively correlated with blood glucose level and the estimated duration of diabetes mellitus. INTERPRETATION AND CONCLUSION: The employed quantitative method demonstrated that patients with diabetes exhibited venule dilation in the upper temporal quadrant, and the duration of diabetes mellitus was positively correlated with blood glucose level. Therefore, the early assessment of retinal microvascular changes is possible prior to the onset of diabetic retinopathy.

Comparative effects of estrogen, raloxifene and tamoxifen on endothelial dysfunction, inflammatory markers and oxidative stress in ovariectomized rats.

AIM: Endothelial dysfunction is considered a premature indication of atherosclerosis and vessel damage and is present in the postmenopausal period. This study compares the influence of estrogen, raloxifene and tamoxifen on factors that affect endothelial function in ovariectomized (OVX) rats. MAIN METHODS: The rats were divided into: SHAM; OVX; OVX+estrogen (0.5 µg/kg/day); OVX+raloxifene (2 mg/kg/day) and OVX+tamoxifen (1 mg/kg/day) groups. The acetylcholine vasorelaxation response was evaluated in the mesenteric vascular bed. The vascular oxidative stress and serum inflammatory cytokine levels were monitored, and analyses of eNOS and iNOS were performed. KEY FINDINGS: The acetylcholine-induced responses obtained in the OVX were lower than those obtained in the SHAM, and all treatments restored this response. l-NAME reduced and equalized the acetylcholine-induced response in all groups. The attenuation of the acetylcholine-induced responses by aminoguanidine was greater in the OVX. Endothelial dysfunction in OVX was associated with oxidative stress and an increase in iNOS and decrease in eNOS expression. Except for the production of reactive oxidative species (ROS) in the OVX+tamoxifen, treatments improved the nitric oxide component of the relaxation response and normalized both the oxidative stress and the expression of those signaling pathway enzymes. Serum levels of TNF-α and IL-6 were increased in OVX, and treatments normalized these levels. SIGNIFICANCE: Raloxifene and tamoxifen have similar anti-inflammatory effects that may be important in improving vascular dysfunction. Tamoxifen did not affect the ROS but improved endothelial dysfunction. The protective effect on endothelial function by these treatments provides evidence of their potential cardiovascular benefits in the postmenopausal period.

Nandrolone decanoate induces cardiac and renal remodeling in female rats, without modification in physiological parameters: The role of ANP system.

UNLABELLED: Anabolic-androgenic steroids are misused, including women, but little is known about the cardiovascular effects of these drugs on females. AIM: Evaluated the effects of nandrolone decanoate (ND), physical exercise and estrogen deficiency on female rats. MAIN METHODS: Female Wistar rats were divided into 8 groups: S and OVX: (SHAM: sham surgery; OVX: ovariectomy, vehicle), SE and OVXE (resistance exercise 5 times a week, vehicle), SD and OVXD (treated with ND, 20 mg/kg/week for 4 weeks); SDE and OVXDE. Treatments were initiated 21 days after surgery. The Bezold­Jarisch reflex was assessed by Phenylbiguanide administration. The right atrium, kidney, and serum were collected for molecular analyses by RT-PCR of atrial natriuretic peptide (ANP), A-type natriuretic peptide receptor (NPR-A) and NPR-C. ELISA assay to estradiol and testosterone concentrations. The gastrocnemius muscle, heart and kidney weights/tibia length were measured.Morphometric analysis of heart was made (H/E) and collagen content of heart and kidney were evaluated using Pirossirius Red. KEY FINDINGS: ND treatment increased ANP expression on atrium and decreased NPR-A expression in kidney. Physical exercise and ovariectomy did not alter this parameter. NPR-C level was reduced in the SDE and OVXDE. Renal and cardiac hypertrophy was observed after ND treatment, with collagen deposition. Plasma estrogen concentrations were reduced and serum testosterone concentrations were increased after ND treatment. SIGNIFICANCE: ANP has an important role in modulating the cardiovascular effects of ND in females. Thismodulating may have occurred by the increasing ANP expression, reducing NPR-A and NPR-C expression levels, and changing sex hormone levels.

Exercise training reduces cardiac dysfunction and remodeling in ovariectomized rats submitted to myocardial infarction.

The aim of this study was to evaluate whether exercise training (ET) prevents or minimizes cardiac dysfunction and pathological ventricular remodeling in ovariectomized rats subjected to myocardial infarction (MI) and to examine the possible mechanisms involved in this process. Ovariectomized Wistar rats were subjected to either MI or fictitious surgery (Sham) and randomly divided into the following groups: Control, OVX+SHAMSED, OVX+SHAMET, OVX+MISED and OVX+MIET. ET was performed on a motorized treadmill (5x/wk, 60 min/day, 8 weeks). Cardiac function was assessed by ventricular catheterization and Dihydroethidium fluorescence (DHE) was evaluated to analyze cardiac oxidative stress. Histological analyses were made to assess collagen deposition, myocyte hypertrophy and infarct size. Western Blotting was performed to analyze the protein expression of catalase and SOD-2, as well as Gp91phox and AT1 receptor (AT1R). MI-trained rats had significantly increased in +dP/dt and decreased left ventricular end-diastolic pressure compared with MI-sedentary rats. Moreover, oxidative stress and collagen deposition was reduced, as was myocyte hypertrophy. These effects occurred in parallel with a reduction in both AT1R and Gp91phox expression and an increase in catalase expression. SOD-2 expression was not altered. These results indicate that ET improves the functional cardiac parameters associated with attenuation of cardiac remodeling in ovariectomized rats subjected to MI. The mechanism seems to be related to a reduction in the expression of both the AT1 receptor and Gp91phox as well as an increase in the antioxidant enzyme catalase, which contributes to a reduction in oxidative stress. Therefore, ET may be an important therapeutic target for the prevention of heart failure in postmenopausal women affected by MI.

Swimming training prevents fat deposition and decreases angiotensin II-induced coronary vasoconstriction in ovariectomized rats.

We investigated the effects of chronic swimming training (ST) on the deposition of abdominal fat and vasoconstriction in response to angiotensin II (ANG II) in the coronary arterial bed of estrogen deficient rats. Twenty-eight 3-month old Wistar female rats were divided into 4 groups: sedentary sham (SS), sedentary-ovariectomized (SO), swimming-trained sham (STS) and swimming-trained ovariectomized (STO). ST protocol consisted of a continuous 60-min session, with a 5% BW load attached to the tail, completed 5 days/week for 8-weeks. The retroperitoneal, parametrial, perirenal and inguinal fat pads were measured. The intrinsic heart rate (IHR), coronary perfusion pressure (CPP) and a concentration-response curve to ANG II in the coronary bed was constructed using the Langendorff preparation. Ovariectomy (OVX) significantly reduced 17-ß-estradiol plasma levels in SO and STO groups (p<0.05). The STO group had a significantly reduced retroperitoneal and parametrial fat pad compared with the SO group (p<0.05). IHR values were similar in all groups; however, baseline CPP was significantly reduced in the SO, STS and STO groups compared with the SS group (p<0.05). ANG II caused vasoconstriction in the coronary bed in a concentration-dependent manner. The SO group had an increased response to ANG II when compared with all other experimental groups (p<0.05), which was prevented by 8-weeks of ST in the STO group (p<0.05). OVX increased ANG II-induced vasoconstriction in the coronary vascular bed and abdominal fat pad deposition. Eight weeks of swimming training improved these vasoconstrictor effects and decreased abdominal fat deposition in ovariectomized rats.

High-frequency transcutaneous electrical nerve stimulation reduces pain and cardio-respiratory parameters in an animal model of acute pain: participation of peripheral serotonin.

The objective of this study was to investigate the effect of high-frequency transcutaneous electrical nerve stimulation (HF-TENS) in antihyperalgesia, assessed through changes of sciatic nerve activity and its effects on cardiorespiratory parameters, using formalin-induced nociception in anesthetized rats. The animals were divided into formalin (FORM) and HF-TENS groups. All rats received injections of 5% formalin (50 µl, right hind-paw). The sciatic nerve activity and cardiopulmonary parameters (mean arterial pressure, heart rate, and respiratory frequency) were measured, and then the serum levels of serotonin (5-HT) were determined by an enzyme-linked immunosorbent assay kit. The formalin injection was able to increase the sciatic nerve activity, heart rate, and respiratory frequency. The treatment with HF-TENS significantly reduced the sciatic nerve activity and respiratory frequency 20 minutes after formalin injection and was able to increase serum 5-HT. Furthermore, when comparing the groups, reductions in the mean arterial pressure, heart rate, respiratory frequency, and sciatic nerve activity were shown at different times. Thus, we concluded that HF-TENS was capable of inducing analgesia, which was most likely related to increased serotonin release. Moreover, we demonstrated that TENS was able to block the adverse cardiovascular and respiratory changes induced by pain. Further neurophysiological studies are necessary to clarify the intrinsic mechanisms underlying HF-TENS-induced analgesia.

Endothelial relaxation mechanisms and oxidative stress are restored by atorvastatin therapy in ovariectomized rats.

The studies on hormone replacement therapy (HRT) in females with estrogen deficiency are not conclusive. Thus, non-estrogen therapies, such as atorvastatin (ATO), could be new strategies to substitute or complement HRT. This study evaluated the effects of ATO on mesenteric vascular bed (MVB) function from ovariectomized (OVX) female rats. Female rats were divided into control SHAM, OVX, and OVX treated with 17ß-estradiol (EST) or ATO groups. The MVB reactivity was determined in organ chambers, vascular oxidative stress by dihydroethidine staining, and the expression of target proteins by western blot. The reduction in acetylcholine-induced relaxation in OVX rats was restored by ATO or EST treatment. The endothelium-dependent nitric oxide (NO) component was reduced in OVX rats, whereas the endothelium-derived hyperpolarizing factor (EDHF) component or prostanoids were not altered in the MVBs. Endothelial dysfunction in OVX rats was associated with oxidative stress, an up-regulation of iNOS and NADPH oxidase expression and a down-regulation of eNOS expression. Treatment with ATO or EST improved the NO component of the relaxation and normalized oxidative stress and the expression of those signaling pathways enzymes. Thus, the protective effect of ATO on endothelial dysfunction caused by estrogen deficiency highlights a significant therapeutic benefit for statins independent of its effects on cholesterol, thus providing evidence that non-estrogen therapy could be used for cardiovascular benefit in an estrogen-deficient state, such as menopause.

Gastric bypass and sleeve gastrectomy: the same impact on IL-6 and TNF-α. Prospective clinical trial.

BACKGROUND: Due to the association between the quantity of adipose tissue and concentrations of interleukin-6 (IL-6) and tumor necrosis factor (TNF-α), this work aimed to assess the effects of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) procedures on serum IL-6 and TNF-α concentrations. METHODS: This study evaluated serum IL-6 and TNF-α levels, as well as routine anthropometric and biochemical values, before and 1 year post-bariatric surgery. Fifty percent of patients (n = 24) underwent RYGB, and 50 % (n = 24) underwent SG. Prior to bariatric surgery, IL-6 and TNF-α mRNA expression levels in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were investigated in obese women. RESULTS: There was a significant reduction (p < 0.05) in all anthropometric and routine biochemical measurements in patients in the RYGB and SG groups 1 year post-surgery. The serum concentrations of IL-6 and TNF-α were reduced following surgery in both groups (p < 0.05). No differences in the relative expression levels of IL-6 and TNF-α were found between SAT and VAT prior to bariatric surgery. CONCLUSIONS: RYGB and SG procedures demonstrated a similar impact on adipokine levels in women 1 year post-surgery. Both techniques may improve the course of chronic diseases and the state of inflammation associated with obesity.

Tibolone has anti-inflammatory effects in estrogen-deficient female rats on the natriuretic peptide system and TNF-alpha.

Cardiovascular and immune system abnormalities have been reported in females with estrogen deficiency. To control these disorders in post-menopausal women, hormone replacement therapy (HRT) has been used. Tibolone has been used as a HRT, but the effects of tibolone on the natriuretic peptide system have not been determined. We investigated the effects of tibolone on the natriuretic peptide system and pro-inflammatory cytokines in ovariectomized (OVX) rats. Female rats were divided into four groups: SHAM, OVX, OVX treated with 17ß-estradiol (OVX+E: 14 days) and OVX treated with tibolone (OVX+T: 14 days) beginning 21 days after ovariectomy. On day 35, blood was collected to determine atrial natriuretic peptide (ANP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) levels. In addition, tissues were collected for determining ANP, natriuretic peptide receptor type-A (NPR-A), and NPR type-C (NPR-C) gene expression levels by RT-PCR. The cytokine levels of both IL-6 and TNF-α were increased in OVX animals. In comparison, IL-6 and TNF-α levels were reduced in OVX+E animals. TNF-α levels were reduced similarly in OVX+T animals, but IL-6 levels remained elevated in this group. The concentrations of ANP in the left atrium tissue and plasma were decreased after ovariectomy, as were ANP mRNA levels in the left atrium and NPR-A mRNA levels in kidney. No variation in NPR-C gene expression in the kidney tissue was observed among the groups. Tibolone and 17ß-estradiol effectively increased plasma ANP and ANP mRNA levels in the left atrium, but did not normalize renal NPR-A levels. Since HRT with tibolone normalizes plasma ANP and serum TNF-alpha levels our results suggest that treatment with tibolone has anti-inflammatory effects and could prevent cardiovascular disease in the long-term.

Raloxifene reduces blood pressure in hypertensive animals after ovarian hormone deprivation.

Raloxifene is a selective oestrogen receptor modulator that has been approved for the prevention and treatment of osteoporosis in post-menopausal women. Studies have revealed several effects of raloxifene on the cardiovascular system, which might contribute to the blood pressure regulatory mechanisms, particularly in the systemic arterial hypertension. Therefore, the aim of this study was to investigate the effects of raloxifene on the blood pressure, renal excretion of water and Na(+) and plasma nitrite/nitrate levels in 2-kidney-1-clip (2K1C) hypertensive female rats. The groups were as follows: hypertensive (2K1C), hypertensive ovariectomized (2K1C + OVX) and hypertensive ovariectomized treated with raloxifene (2K1C + OVX + R). Seven days after the surgery that produced menopause, 2K1C hypertension was produced in anaesthetized animals. Seven days after the clip application, the rats were put into metabolic cages to allow for the measurement of water ingestion and diuresis, and raloxifene was administered (2 mg/kg/day i.p., for 7 more days). We found a large reduction (p < 0.01) in mean arterial pressure (197 ± 6 to 164 ± 2 mmHg), an increase in renal excretion of sodium and water (p < 0.05) and an increase in plasma levels of nitrite/nitrate in 2K1C + OVX + R animals, when compared with the 2K1C (23.4 ± 1 versus 14 ± 0.5 nmol/mL; p < 0.01, respectively). These findings suggest that raloxifene exerted its antihypertensive effect, at least in part, by improving the renal excretion of sodium and water.

Cardiovascular risk factors, their associations and presence of metabolic syndrome in adolescents.

OBJECTIVE: To evaluate the occurrence of metabolic syndrome (MS) and independent associated risk factors in adolescents in the city of Vitória, Brazil. METHODS: We assessed 380 adolescents aged 10 to 14 years attending public schools. Body mass index and blood pressure at rest were measured. Fasting plasma concentrations of total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides and glucose were also obtained. RESULTS: The prevalence of overweight was 9.6% for boys and 7.4% for girls, while obesity was found in 6.2 and 4.9%, respectively. Triglyceride concentrations were borderline or high in 6.8 and 3.4% of the boys and in 11.8 and 5.9% of the girls. HDL-cholesterol was below recommended levels in 8.5% of the boys and in 9.9% of the girls. Blood pressure at rest was borderline for 5.1% of the boys and 7.9% of the girls, while 3.4% of both boys and girls were hypertensive. Fasting glycemia was high in 0.6% of the boys and in 0.5% of the girls. In the group studied, 2.8% of the boys and 2.5% of the girls had two risk factors associated with MS. Prevalence of MS was 1.1% for boys and 1.5% for girls, and overall prevalence was 1.3%. CONCLUSIONS: MS and associated cardiovascular risk factors are serious clinical conditions in this age group. A significant number of adolescents showed borderline results, which may increase the prevalence of MS or independent risk factors in the short term. More investments should be made in primary prevention, considering that early diagnosis is an issue of fundamental importance.