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A disfunção ventricular direita pós-infarto do miocárdio está associada com o desenvolvimento da insuficiência cardíaca
(Universidade Federal do Espírito Santo, 2010-05-07) Fernandes, Aurélia Araújo; Zornoff, Leonardo Antônio mamede; Stefanon, Ivanita; Alessandra Simao Padilha; Vassallo, Dalton Valentim; Pereira,Fausto Edmundo Lima
Heart failure (HF) is the major cause of death and morbidity after myocardial infarction (MI) that can result in reduced cardiac output, increased venous pressure and cardiac remodeling. Usually, the left ventricle failing causes right dysfunction being related to greater risk of hospitalization. It has been suggested that assessment of right ventricle (RV) function is of important value to prognostic of HF after MI. Therefore, the aim of this study was to assess right ventricle contractility early (one week) and late phase (eight weeks) after MI. MI with signal of HF (HF group) and without signal of HF (Inf group) were compared to a sham-operated group (sham). Wistar male rats were anaesthetized with Ketamine (50 mg/kg) and Xylazine (5 mg/kg), i.m., and MI was induced through left coronary artery ligation at 3 mm of its origin. After 1 and 8 weeks the rats was anaesthetized with urethane (1.2 g/kg i.p.) and a catheter was inserted into the aorta and left ventricle to pressures measurements using a pressure transducer (TSD 104A) coupled to a Biopac MP100 system. Strips from the right ventricle were removed and attached to an isometric transducer and superfused at 30ºC with Krebs solution, stimulated at 0.5 Hz and 80 mV. The experimental protocols were approved by the local animal ethics committee (CEUA-EMESCAM). Both infarct groups presented same scar size (Inf 1 week= 32.4 ± 3; HF 1 week=33.7 ± 2.2; Inf 8 weeks= 26.5 ± 1.1; HF 8 weeks= 25 ± 0.9). The scar size did not have correlation with HF signals (left ventricle end diastolic pressure (LVEDP), increased lung weight and body weight ratio (LW/BW) and right ventricle to body weight ratio (RV/BW) neither with RV contractility. The LVEDP increased in HF group but not in the Inf group early (1 week: HF=15 ± 1*; Inf=5.2 ± 0.8; Sham=3,7 ± 0,6 mmHg) and late after MI (8 weeks: Hf=16 ± 2.5*, Inf- 7.5 ± 0.7; Sham= 5.2 ± 0.8 mmHg), *P< 0.05 ANOVA one way, post hoc Tukey. In the HF group LW/BW and RV/BW ratio was increased in the late phase, but not in the early phase after MI. The body weight was smaller in the HF group at 1 week, but similar to sham 13 and Inf 8 weeks after MI. Therefore, there was a negative correlation between force development in the RV strips and body weight in both early and late phase after MI. The inotropic responses to Ca2+ and Isoproterenol were preserved in HF group one week after MI and reduced at 8 weeks (8 weeks; CaCl2 2.5 mM: sham= 157 ± 18.4; Inf= 138 ± 17.3; HF= 62 ± 10.3 g/g P<0.05; Isoproterenol 10- 5 M: sham = 149 ± 14; Inf = 137 ± 18.7; HF = 58 ± 8.1 g/g P<0.05). Inversely, in the Inf group, the positive intropic response was reduced in the early phase and reduced in the late phase (1 week; CaCl2 2.5 mM: Sham= 186 ± 8.3; Inf = 135 ± 11.7; HF= 158 ± 13.1 g/g; P<0.05; Isoproterenol 10-5 M: Sham= 145 ± 9.9; Inf= 108 ± 10.8; HF= 166 ± 12 g/g P<0.05). The Ca2+ handling proteins expression (sarcoplasmatic reticulum calcium pump (SERCA-2a), phosfolamban (PLB total), PLB phosphorylated and Na+ /Ca2+ exchange) were not different among the groups in the early phase. But, in the late phase there was a SERCA-2a overexpression and an higher SERCA/PLB ratio just in the Inf group. In conclusion, the scar size did not correlate with HF signals neither with RV contractility. The RV dysfunction was found in the late phase after MI in rats with HF. However, the rats with HF maintain the RV function in early phase after MI. The infarct rats without HF maintained the RV contractility and increase SERCA-2a expression in the late phase after MI. The different inotropic βadrenergic response between the groups with and without HF could be induced by different mechanisms involving upregulation and downregulation of the βreceptors during the early and late phase after MI.
A Exposição Crônica e Baixas Doses de Cloreto de Mercúrio Altera a Reatividade Vascular da Artéria Aorta de Ratos. Papel das Espécies Reativas do Oxigênio e dos Prostanóides da Via da Ciclooxigenase .
(Universidade Federal do Espírito Santo, 2009-05-07) Pecanha, Franck Maciel; Vassallo, Dalton Valentim; Stefanon, Ivanita; Pereira, Fausto Edmundo Lima; Cibin, Francielli Weber Santos
Mercury exposure produces toxic effects in central nervous system and kidneys. Recently these toxic effects were associated to cardiovascular events but the underlying mechanisms are not well explored. The main purpose of this study was to investigate if mercury exposure at low doses alters vasoconstrictor prostanoids production from cyclooxygenase-2 (COX-2) and its contribution to phenylephrine vasoconstrictor responses and acetylcholine vasodilator responses. For this were developed an experimental model of exposure to low doses of mercury chloride (HgCl2) and evaluated the effect of this exposure on systolic blood pressure (SBP), the participation of products derived from the endothelium, prostanoids derived from the cyclooxygenase-2 (COX-2), reactive oxygen species (ROS) and the reninangiotensin system in vascular reactivity in conductance arteries. Aortic segments from 3-month old Wistar rats daily treated with HgCl2 (1st dose 4.6 µg/kg, subsequent dose 0.07 µg/kg/day, i.m) or vehicle for 30 days were used. The vascular reactivity experiments were performed in an organ bath, the atomic absorption spectrometry for determination of blood concentration of mercury, RT-PCR and Western blot to verify the gene and protein expression, confocal microscopy analyzed levels of superoxide anion and structure of arteries. A commercial kit used to determine the production of prostanoids derived from COX-2 pathway. The activity of angiotensinconverting enzyme (ACE) was measured by fluorometry method and SBP by tail plethysmography. Blood levels of mercury at the end of treatment were 7.97 ± 0.59 ng/ml. Mercury treatment did not affect systolic blood pressure, but increased phenylephrine contractile responses, reduced acetylcholine-induced vasodilatation and did not change the vasodilatation by the nitric oxide donor, DEA-NO, in aortic rings. The contractile prostanoids derived from COX-2 pathway, reactive oxygen species (ROS) and increased plasmatic ACE activity were related to these responses. Increased production of EROS, increased plasma ACE activity, increased gene expression of mRNA for COX-2 and increased production of contractile prostanoids (PGE2 and TXA2) derived from COX-2 were observed in animals exposed to mercury and reinforce the hypothesis of a greater involvement of these pathways in the alteration of vascular response to phenylephrine. In the presence of superoxide dismutase (SOD) the vasodilator response to acetylcholine was improved in rats of the mercury group, indicating that endothelial dysfunction appears to be responsible for the increased production of EROS. The extracellular SOD (EC-SOD) expression was increased by exposure to mercury. These results suggest that this new experimental model of chronic exposure at low concentrations of HgCl2 promotes endothelial dysfunction due to the reduced bioavailability of NO induced by increased oxidative stress, and increase the contractile response to phenylephrine with greater involvement of the reninangiotensin system, EROS and contractile prostanoids derived from COX-2 pathway in this response. These results help to clarify the mechanisms by which mercury at low doses exerts toxic effects on the cardiovascular system and can be considered a risk factor for development of cardiovascular disease.
Ação moduladora da tibolona no sistema de peptídeos natriuréticos: Implicações cardiovasculares e imunológicas
(Universidade Federal do Espírito Santo, 2010-11-24) Garcia, Ana Raquel Santos de Medeiros; Andrade, Tadeu Uggere de; Bissoli, Nazaré Souza; Reis, Adelina Martha dos; Boechät, Giovanna Assis Pereira; Padilha, Alessandra Simão
Cardiovascular and immune system abnormalities have been reported in females with estrogen deficiency. Nevertheless, the capacity of the exogenous estrogen therapy to manage these hazard effects in postmenopausal women is still to be better investigated. Objective: this study is addressed to determine the abnormalities on the natriuretic peptide system in ovariectomized rats with and without tibolone reposition therapy, and if these changes are or not related with cardiovascular and immunological parameters. Materials and Methods: female rats with the average weight of 160-180 g were used and divided into four groups (n = 7 per group): SHAM, ovariectomized (OVX), OVX treated with 17β-estradiol (EST) and OVX treated with tibolone (TIB). The treatment period was 14 days with TIB (1.5 mg / kg / day) and EST (0.5 mg / kg / day), after 21 days of the ovariectomy procedure. At the end of treatment, the animals were euthanized, the thoracic aorta was isolated, and rings of 4-5 mm were removed. Rings with endothelium, were placed in an isolated organ tank with Krebs solution. Dose-response curves to phenylephrine (PHE) and acetylcholine (ACH) were obtained for assessment of vascular reactivity. Upper segment of the thoracic aorta was used for analysis of protein expression of eNOS by Western Blotting. The kidneys, the atria and blood were collected for further analysis. Plasma levels of atrial natriuretic peptide (ANP) were measured by radioimmunoassay (RIA) and serum cytokines (IL-6 and TNF-α) by ELISA. Atria were removed for analysis by RIA of ANP and atrial ANP mRNA by RT-PCR. The kidneys were used for analysis of mRNA of type A receptor (NPR-A) and C (NPR-C) by RT-PCR. Data were presented as mean ± standard error of mean. Statistical analysis of the reactivity of aortic rings was performed by analysis of variance (ANOVA), and one or two way, followed by post-hoc test of Tukey. For the peptides system data it was performed one-way analysis of variance (ANOVA) followed by post hoc Newman-Keuls, and for eNOS it was used one-way analysis of variance (ANOVA) followed by Fisher's post hoc test. Significance levels were p<0,05. Results: the OVX group showed increase of contractile response to PHE compared to the SHAM group, and the TIB and EST groups were able to normalize this response (Emax - SHAM: 91,0 ± 3,9; OVX: 140,0 ± 5,5; EST: 115,4 ± 3,7; TIB: 113,2 ± 5,1 - % Tension). The endothelium-dependent relaxation (dose-response curves to ACH) was similar for all groups. The OVX, EST and TIB groups showed no difference in the eNOS protein expression compared with the SHAM group, however, serum levels of IL-6 and TNF-α were increased in ovariectomized females. However, the treatments with EST and TIB were able to decrease these levels compared to the SHAM group, except the levels of IL-6 which remained high in the TIB group (TNF-α: SHAM 20.3 ± 2.0, OVX 31.0 ± 5.0, 17.6 ± EST 2.0; TIB: 20.5 ± 3.1 / IL-6: SHAM 19.3 ± 6.0, 32.8 ± 5.0 OVX, EST 20.0 ± 3.0; TIB: 34.4 ± 2.8 pg / ml). The plasmatic and left atrial levels of ANP (ANP plasma: 263.3 ± 53.3 SHAM, OVX 92.5 ± 19.5, 247.3 ± 29.9 EST; TIB: 285.7 ± 60.4 pg / ml / left atrial ANP: SHAM 5.68 ± 0.35; OVX 3.48 ± 0.40, 0.97 ± 6:48 EST; TIB: 3.59 ± 0.25 mg / mg protein), the mRNA expression of ANP left atrial (SHAM 91.3 ± 4.4, OVX 40.0 ± 10.1; 122.3 ± 12.0 EST; TIB: 167.9 ± 25.7 AU) and NPR-A (SHAM 5.20 ± 12:00; OVX 0.68 ± 0.11; EST 0.92 ± 0.28; TIB: 2.04 ± 1.4 AU) were depressed after ovariectomy, and NPRC did not change. The treatment normalized these parameters, except that the TIB group did not normalize the levels of atrial ANP. Conclusion: data from this study show, for the first time, that tibolone treatment after ovariectomy influence the natriuretic peptide system and the inflammatory cytokines. Tibolone was able to normalize the levels of ANP and its atrial expression as well as reduce levels of TNF-α. Additionally, the results show that Hormonal Therapy used in this study partially normalized the changes in vascular reactivity, possibly through regulation of the peptide system and inflammatory cytokines.
Ácido Linoleico Reduz a Reatividade Vascular e Melhora a Disfunção Vascular de Artérias Mesentéricas de Ratos Hipertensos
(Universidade Federal do Espírito Santo, 2018-10-04) Nunes, Dieli Oliveira; Ribeiro Junior, Rogerio Faustino; Padilha, Alessandra Simao; Pereira, Fausto Eduardo Lima; Mill, José Geraldo; Stefanon, Ivanita
Omega-6 polyunsaturated fatty acids are well known for their important role in many physiological functions and in reducing the risks of cardiovascular diseases, especially linoleic acid (LA). Therefore, we aimed to investigate the effect of linoleic acid (LA) treatment on the blood pressure and function of mesenteric resistance arteries (MRA) in spontaneous hypertensive rats (SHR). Male SHR were treated daily with LA (15 mg/kg) or vehicle (control) for 15 days. Compared with controls, LA treatment decreased blood pressure (SBP (mmHg) - Control: 139 ± 1,8 vs LA: 128,4 ± 1,7; DBP (mmHg) - Controle: 78,6 ± 1,1 vs AL: 70,1 ± 3,7 and showed the following in MRA: (1) increased lumen and external diameter, (2) decreased wall:lumen ratio and wall thickness, (3) decreased stiffness and (4) less collagen deposition. LA treatment reduced the contractile response to phenylephrine, although there were no changes observed in MRA in regard to the acetylcholine or sodium nitroprusside responses. Incubation with L-NAME leftshifted the reactivity to phenylephrine only in the MRA treated group, suggesting that LA treatment can improve NO bioavailability, which was confirmed by NO “in situ” quantification analyses. Incubation with tiron decreased vascular reactivity to phenylephrine in MRA in LA rats, which was accompanied by decreased superoxide anion production. Moreover, incubation with indomethacin (nonselective COX inhibitor), NS 398 (COX-2 specific inhibitor), furegrelate (TXA2 synthase inhibitor), SQ 29.548 (TP receptor antagonist) and SC 19220 (EP1 receptor antagonist) reduced the vasoconstrictor responses to phenylephrine in MRA in the treated group. These results were accompanied by a reduction in COX-2 protein expression. In conclusion, these findings show that LA treatment decreases blood pressure, accompanied by structural and functional changes in resistance arteries of SHR rats. These functional changes involve NO bioavailability and reduction in superoxide anion production. At last, the improvement of endothelial dysfunction and structural changes in this hypertension model may be responsible for the reduction in blood pressure.
ÁCIDO ÚRICO SÉRICO EM CRIANÇAS E ADOLESCENTES: DISTRIBUIÇÃO E ASSOCIAÇÃO COM FATORES DE RISCO CARDIOVASCU
(Universidade Federal do Espírito Santo, 2020-03-06) Moulin, Stephanie Rezende Alvarenga; Mill, Jose Geraldo; https://orcid.org/000000020987368X; http://lattes.cnpq.br/2497419234600362; https://orcid.org/; http://lattes.cnpq.br/; Vassallo, Dalton Valentim; https://orcid.org/; http://lattes.cnpq.br/7749285591179880; Sartorio, Carmem Luiza; https://orcid.org/; http://lattes.cnpq.br/1299417616233163; Baldo, Marcelo Perim; https://orcid.org/; http://lattes.cnpq.br/; Cristo, Valeria Valim; http://lattes.cnpq.br/3210373469770019
BACKGROUND: Hyperuricemia in adults is associated with cardiovascular diseases. However, there is lack of information regarding serum uric acid (SUA) determinants in children and adolescents. Our purpose was to determine the SUA distribution in schoolchil
Alterações cardiovasculares induzidas pela peçonha da serpente Bothrops leucurus
(Universidade Federal do Espírito Santo, 2018-04-05) Naumann, Gustavo Baptista; Sanchez, Eládio Flores; Figueiredo, Suely Gomes de; Borges, Márcia Helena; Pires, Rita Gomes Wanderley; Gouvêa, Sonia Alves; Bissoli, Nazaré Souza
Bothrops leucurus (white tail jararaca) is the main responsible for ophidian accidents in the northeastern region of Brazil and northern Espírito Santo. Several studies have evaluated the biochemical features of this snake’s venom, as well as its local effects. However, systemic effects – in particular cardiovascular effects – remain rather poorly explored. In the present study, we sought to investigate the acute cardiovascular activities induced by B. leucurus venom (VB) in vivo and in vitro. In anaesthetized rats it was demonstrated that BlV (10-100µg/kg) induces immediate and transient hypotension, while maximum response was observed in 5 min and a return to baseline was observed in ≈ 20 minutes. No change in the heart rate of the animals was observed. In vitro effects were evaluated on pre-contracted mesenteric artery rings with phenylephrine, employing a resistance myograph.
Análise da precisão e da aplicabilidade do consumo de oxigênio de reserva durante o exercício aeróbio contínuo nas intensidades de 50% a 80% do consumo máximo de oxigênio
(Universidade Federal do Espírito Santo, 2007-03-27) Santos, Miguel Angelo Alves dos; Orientador1; https://orcid.org/; http://lattes.cnpq.br/; 1º membro da banca
The main objective of this study was to evaluate the accuracy and the applicability of oxygen consumption reserve (VO2R) in the prescription of continuous aerobic exercise for the maximal oxygen consumption (VO2max) intensities of 50%, 60%, 70%, and 80%. Following ergoespirometry, the physical training speeds corresponding to 50%, 60%, 70%, and 80% VO2R were calculated using the equation proposed by ACSM for running and walking in 60 volunteers – 30 males and 30 females – aged 23 ± 3.4 and 21.7 ± 4.1 respectively. After the calculations were done, the volunteers performed continuous aerobic exercise (running or walking) for 30 minutes in a random sequence of the said intensities with intervals of 48 hours between them. During the exercise performance, oxygen consumption was collected. The VO2 consumption collected during the aerobic exercise was called measured oxygen consumption reserve (VO2Rm) for the purpose of comparing VO2R calculations with VO2 consumption at the same exercise intensity. The criteria used for determining the equation accuracy were the following: a) Student’s t test; b) evaluation of the correlation coefficient; c) analysis of estimate standard error of the inclination of the straight line of linear regression. The level of significance used was p< 0.05. Data demonstrated that VO2R and VO2Rm were similar in all intensities. However, the VO2R median values were always higher at each intensity studied than those of VO2Rm (3.4%, 4.2%, 9.2%, and 2.2% in the male group and 9.9%, 3.3%, 7.7%, and 9.7 % in the female group). There was no significant difference between the heart rate measured in the blood lactate (BL) and the heart rate at 70% of HRmaxE and 70% of HRmaxM. The heart rate values prescribed indirectly 85% of HRmaxE and 85% of HRmaxM underestimate the heart rate in the RCP by approximately 6.5% (male group) and 9.1% (female group). The VO2 values prescribed indirectly overestimate by approximately 36.7% (male group) and 66.3% (female group) when VO2 at 60% of the estimated oxygen maximal consumption (VO2maxE) is used and by 18% when VO2 at 60% of VO2maxM is used compared to VO2 values in BL, both groups. There was no significant difference between VO2 in RCP and VO2 at 80% of VO2maxM; however, VO2 in RCP was approximately 9.2% higher in the male group and 6.5% lower in the female group. We came to the conclusion that the oxygen consumption reserve equation demonstrates a good correlation with the VO2 consumed during continuous aerobic exercise; however, the said equation tends to overestimate the aerobic exercise intensity mainly in individuals with poor physical condition. Moreover, the use of both VO2maxE and HRmaxE overestimates the values found, which may predispose to a premature metabolic acidosis, and, as a result of that, cause an overload to the cardio-vascular system. The results suggest that adequate prescriptions of intensities for aerobic exercising are more efficient and safer when determined by ergoespirometry.
Análise do efeito do Sildenafil sobre células-tronco hematopoiéticas em camundongos ateroscleróticos
(Universidade Federal do Espírito Santo, 2017-12-21) Rodrigues, Bianca de Paula e; Vasquez, Elisardo Corral; Padilha, Alessandra Simão; Amorim, Fernanda Gobbi; Campagnaro, Bianca Prandi
A decline in the functionality of stem cells may be a key component in the pathogenesis of cardiovascular diseases. In atherosclerosis, there is an increase in endogenous genotoxic agents, such as reactive oxygen species (ROS), which can cause oxidative damage in DNA. Considering previous report that sildenafil, an inhibitor of phosphodiesterase 5 (PDE5), have antioxidant effects, in the present study we evaluated the effect of this drug on ROS levels, on pro-oxidant and antioxidant systems, on genotoxicity, on DNA repair kinetics and on apoptosis in hematopoietic stem cells (HSC) of atherosclerotic apoE knockout mice (apoE-/-). For this study were used male 20-week old apoE-/- mice. Animals were distributed into three different groups: apoE−/− mice administered with the PDE5 inhibitor sildenafil (apoE−/− sildenafil, Viagra® , 40 mg/kg/day, for 3 weeks, by oral gavage, n=25), apoE-/- mice administered with vehicle (apoE-/- vehicle, n=25) and Wild-type C57Black/6 mice (C57 vehicle, n=25). Then, animals were euthanized, blood collected for analysis of the lipid profile. The HSC were isolated by cell culture for assessed of ROS production, DNA damage, DNA repair kinetics and apoptosis by flow cytometry. Statistical comparisons were done by ANOVA, followed by Bonferroni’s post hoc test.
Análise do proteoma mitocondrial de células do fígado de camundongos apoE knockout tratados com sildenafil
(Universidade Federal do Espírito Santo, 2017-05-19) Menezes, Thiago Nunes de; Orientador1; https://orcid.org/; http://lattes.cnpq.br/; Borges, Márcia Helena; Vasquez, Elisardo Corral; Fronza, Marcio; Bissoli, Nazare Souza
The role of plasmatic lipids in the chronic disease may be associated with oxidative stress, which is characterized by redox imbalance. Proteins are molecules involved in almost all biological phenomena and the understanding of the protein regulation may be a source of new therapeutic strategies. Thus, the aim of the present work was analyse the mitochondrial protein expression in 18-weeks old sildenafil-treated apoE-/- mice as compared to non-treated animals. Previously, the apoE-/- mice presented a plasma lipid profile characteristic of dyslipidemia, and the triacylglycerol, total cholesterol, LDL and VLDL levels were 5, 14, 6 and 36 times higher than observed from control group (C57), which was not reverted by treatment with sildenafil. Flow cytometry showed in liver cells increased levels of intracellular reactive oxygen species of superoxide anion (~82%), hydrogen peroxide (~60%), peroxinitrite (~53%) as well as increased apoptotic cells (from ~2% to ~19%). The treatment was able to prevent the production of analysed ROS and reduced the apoptotic cells, restoring the pattern observed in C57 group. It suggests that sildenafil presents an antioxidant action. Differential two-dimensional electrophoresis coupled with mass spectrometry was applied to study the changes in mitochondrial protein profile in both conditions.
Apocinina e Espironolactona Previnem o Aumento de Estresse Oxidativo Mitocondrial e da Via da NADPH Oxidase e Melhoram a Contratilidade Miocárdica em Ratas Ovariectomizadas
(Universidade Federal do Espírito Santo, 2019-05-06) Rodrigues, Samya Mere Lima; Stefanon, Ivanita; https://orcid.org/0000-0003-2638-5183; http://lattes.cnpq.br/8456612999765726; https://orcid.org/0000-0003-2160-8413; http://lattes.cnpq.br/2687624857190195; Futuro Neto, Henrique de Azevedo; https://orcid.org/; http://lattes.cnpq.br/; Bissoli, Nazare Souza; https://orcid.org/0000-0001-6887-5290; http://lattes.cnpq.br/8865368585732583; Soares, Aurelia Araujo Fernandes; https://orcid.org/0000000199451909; http://lattes.cnpq.br/5478728158150003; Padilha, Alessandra Simao; http://lattes.cnpq.br/7658998034219799
This study aimed to identify if the production of reactive oxygen species by NADPH oxidase and mitochondria trigger the dysfunction in this model of female sex hormone deprivation for 60 days. Wistar rats with ≈7 weeks old and randomly divided into 4 groups: Sham, Ovx, Ovx + Apocynin (Ovx + Apo) and Ovx + Spironolactone (Ovx + Spiro). The results showed that Apo was able to prevent body weight gain in the animals. Spiro was unable to prevent body weight gain. Evaluating myocardial contractility, we observed that Apo treatment was able to prevent the reduction of myocardial contractility observed in Ovx animals (Sham: 605.4 ± 10.37 g - Ovx: 358.3 ± 21.23 * g / Ovx + Apo (dF / dt +: Sham mg vs. Ovx * mg / Ovx + Apo # mg / mg p <0.01) and ( dF / dt-Sham mg vs. Ovx * mg / Ovx + Apo # mg / mg, p <0.01); and the treatment with Spiro also presented preventive capacity (Sham: 712 ± 14.31 g - Ovx: 281.3 ± 7.99 * g / Ovx + Spiro: 726.1 ± 4.39 # g / g, p <0.01). All groups showed positive inotropic strength in response to Ca 2+ and Isoproterenol, but the Ovx groups treated with Apo and / or Spiro presented similar responses to the Sham group and in the Ovx group such responses were reduced (Ca2+ - 1.25-Sham: 484 ± 20.52 g vs Ovx: 247 ± 12.23 * g vs. Ovx + Apo: 494 ± 32.40 g / g, p <0.01) - (Ca2+ - 1.25-Sham: 450.81 ± 38, 08 g vs. Ovx: 285.29 ± 23.89 * g vs Ovx + Spiro: 544.71 ± 57.06 # g / g, p <0.01). Response to the β-adrenergic agonist isoproterenol in the Ovx group treated with Apo was similar to the Sham group and the untreated Ovx animals showed reduction in the contractile response (Iso Log [M] 10-3-Sham: 592.73 ± 26.59 gOvx: 345.43 * ± 31.12g / Ovx + Apo: 627.51 ± 21.44 # g / g, p <0.05). In the Ovx animals the response to Iso was reduced compared to Sham and the treatment with Spiro prevented such reduction (Iso Log [M] 10-3 -Sham: 607.19 ± 22.87 g - Ovx: 304.98 ± 28, 68 * g / Ovx + Spiro: 666.12 ± 71.24 g / g, p <0.05). Expression of Serca 2a protein was reduced, and expression of phospholabam (PLB) and Nox4 were increased in Ovx animals compared to Sham and Apo and / or Spiro treatment reversed the reduction of Serca 2a expression (Sham: 1.39 ± 0.12 - Ovx: 0.86 ± 0.05 * / Ovx + Apo: 1.26 ± 0.08 # - Ovx + Spiro: 1.28 ± 0.10 # p <0.05) and reduced PLB and Nox4 (PLB-Sham: 1.12 ± 0.06 - Ovx: 1.63 ± 0.08 * / Ovx + Apo: 0.99 ± 0.07 # - Ovx + Spiro: 1 , 0.64 ± 0.05 - Ovx: 1.22 ± 0.15 * / Ovx + Apo: 0.64 ± 0.07, - Ovx + Spiro: 0.65 ± 0.10%, p <0.05). Ovx animals had higher superoxide anion production when compared to Sham, and Apo and Spiro treatments reduced this increase (Sham: 3.85 ± 0.40 - Ovx: 9.74 ± 1.03 * / Ovx + Apo: 4.16 ± 0.48 # - Ovx + Spiro: 2.99 ± 0.21 #, p <0.01). The maximum mitochondrial respiration rate in response to the substrates (glutamate + malate: G + M, palmitoyl Lcarnitine: PC and pyruvate: P + M) of the IFM subpopulations in State 3 were reduced in the Ovx vs Sham group, and the treatments with Apo and Spiro prevented such reduction (Ovx vs. Ovx Apo / or Spiro Ovx, p <0.05) in the SSM subpopulations in State 3 only in response to the G + M substrate the maximum respiration rate was shown reduced in the Ovx vs Sham animals and preventive treatments with Apo / Spiro reversed the reduction of the maximum respiration rate. In State 4 of the IFM and SSM subpopulations the maximal respiration rate was increased in the Ovx vs Sham groups in the presence of all substrates and the Apo / or Spiro treatments reduced this increase. A reduction in the expression of the mitochondrial complexes I, IV and III in the Ovx subpopulation IFM was observed, and the non-reversible Apo / or Spiro treatments were able to reverse the reduction (Complex I: Sham: 0.96 ± 0.08- Ovx: 0.53 ± 0.08 / Ovx + Apo: 0.75 ± 0.11 * -Ovx + Spiro: 0.59 ± 0.08 * μg - Complex IV: Sham: 1.22 ± 0.17- Ovx: 0.80 ± 0.09 * / Ovx + Apo: 0.95 ± 0.09 * -Ovx + Spiro: 0.70 ± 0.07 * μg - Complex III: Sham: 1.19 ± 0.17 -Ovx: 0.79 ± 0.09 * / Ovx + Apo: 0.74 ± 0.09 * -Ox + Spiro: 0.73 ± 0.05 * μg, p <0.05). In the SSM subpopulation of the Ovx + Spiro group there was a reduction in the expression of Complexes I, IV and III (Complex I: Sham: 1.30 ± 0.18- Ovx: 0.99 ± 0.18 / Ovx + Apo: 1.07 ± 0.06-Ovx + Spiro: 0.93 ± 0.09 * μg, p <0.05 - Complex IV: Sham: 1.30 ± 0.20-Ovx: 0.99 ± 0.13 / Ovx + Apo: 0.86 ± 0.09 * - Ovx + Spiro: 0.79 ± 0.08 * μg, p <0.05 - Complex III: Sham: 1.33 ± 0.19-Ovx: 0.99 ± 0.12 / Ovx + Apo: 1.08 ± 0.08-Ovx + Spiro: 0.02 ± 0.07 * μg, p <0.05). Expression of the MnSOD and Catalase antioxidant proteins were reduced in the Ovx vs. Sham rats and Apo or Spiro treatments prevented the reduction of the expression of the proteins mitochondrial CTE Tfam and PGC1α were reduced Ovx vs Sham and Apo or Spiro treatments prevented such reduction. Our results confirmed that estrogen hormone deprivation increases oxidative stress both by NADPH oxidase and mitochondria, and the preventive treatments with Apocynin and Spironolactone had antioxidant action and were able to prevent damage in myocardial contractility.
Associação do alisquireno e L-arginina melhora a atividade simpática e função renal na hipertensão renovascular
(Universidade Federal do Espírito Santo, 2015-02-27) Tiradentes, Renata Viana; Abreu, Glaucia Rodrigue; Mauad, Hélder; Neto, Henrique de Azevedo Futuro; Bissoli, Nazare Souza
Renovascular hypertension is characterized by increased renal sympathetic activity, angiotensin II, and by endothelial dysfunction. The purpose of this study was to determine the role of renal sympathetic nerve activity (RSNA) in mediating the anti-hypertensive effects of aliskiren (ALSK) and L-arginine (L-ARG) in a rat renovascular hypertension model. Hypertension was induced by clipping the right renal artery, and the following 5 groups were divided: Sham operated; 2-kidney, 1-clip (2K1C); 2K1C plus ALSK; 2K1C plus L-ARG; and 2K1C plus ALSK+ L-ARG. The systolic blood pressure (SBP) of 2K1C rats increased from 114.4±5.2 to 204±12.7 mmHg, (P< 0.05) and was only reduced by ALSK+L-ARG treatment (138.4±4.37 mmHg). The 2K1C hypertension increased the baseline RSNA (SHAM: 62.4±6.39 vs 2K1C: 97.4±8.43%). L-ARG or ALSK+L-ARG treatment significantly decreased baseline RSNA (2K1C L-ARG:70.7±2.39; 2K1C ALSK+L-ARG: 69.3±4.23%), but ALSK treatment alone did not (2K1C ALSK: 84.2±2.5%). Urinary water, Na+ , Cl- and urea excretion were similar in the 2K1C L-ARG, 2K1C ALSK+L-ARG and SHAM groups. The combination of ALSK+L-ARG restored urine flow and increased the glomerular filtration rate. The nNOS expression in the non clipped kidney was significantly increased in 2K1C ALSK+L-ARG rats. In conclusion, combined ALSK+L-ARG treatment normalizes SBP and prevents renal dysfunction in 2K1C hypertensive rats, an effect that can be partially attributed to reduced RSNA.
Aumento da Expressão do receptor tipo Toll 4 pela angiotensina II contribui para a hipertensão e disfunção vascular através da produção de espécies reativas de oxigênio.
(Universidade Federal do Espírito Santo, 2014-09-22) Batista, Priscila Rossi de; Vassalo, Dalton Valentin; Barauna, Valerio Garrone; dos Santos, Leonardo; Fausto, Edmundo Lima Pereira; Davel, Ana Paula Couto
Hypertension is considered as a chronic inflammatory disease, with adaptive immunity being an important mediator of this process. Toll like receptor 4 (TLR4) - that triggers the innate immunity - may have a role in the development of several cardiovascular diseases; however, little is known about its participation in hypertension. We aimed to investigate whether TLR4 activation due to the increased activity of the renin-angiotensin system (RAS) contributes to hypertension and its associated vascular damage. For this, we used the following groups: Wistar and SHR controls; SHR losartan (losartan 15 mg/kg•day); Wistar and SHR IgG (non-specific IgG 2a, 1 μg/day); SHR anti-TLR4 (antibody anti-TLR4, 1 μg/day). We also used aortic segments and vascular smooth muscle cels (VSMCs) from Wistar and SHRs controls. TLR4 mRNA levels were greater in aortic segments and VSMCs from SHRs compared with Wistar rats; losartan treatment reduced those levels in SHRs. Treatment of the SHRs with the anti-TLR4 antibody: 1) reduced the increased blood pressure, heart rate and phenylephrine-induced contraction while it improved the impaired acetylcholine-induced relaxation in aortic rings; 2) increased the potentiation of phenylephrine contraction after endothelium removal; and 3) abolished the inhibitory effects of tiron, apocynin and catalase on phenylephrine-induced response as well as its enhancing effect of acetylcholine-induced relaxation. In SHR VSMCs, angiotensin II increased TLR4 mRNA levels, and losartan reduced that increase. CLI095, a TLR4 inhibitor, mitigated the increases in NOX-4, NADPH oxidase activity, superoxide anion production, COX-2 gene and protein expression, migration and proliferation that were induced by angiotensin II. In conclusion, TLR4 pathway activation due to increased RAS activity is involved in hypertension and by inducing oxidative stress contributes to the endothelial dysfunction associated to this pathologic process. These results suggest that TLR4 and innate immunity may play a role in hypertension and its associated end-organ damage.
Avaliação cardiorrespiratória em ratos submetidos à convulsão por eletrochoque
(Universidade Federal do Espírito Santo, 2010-10-28) Furtado, Danielly Peres; Mauad, Helder; Cabral, Antônio de Melo; Antonio Carlos Avanza Junior; Vassalo, Dalton Valentim; Calil, Osmar Araújo
The aim of this study was to evaluate the cardiopulmonary changes after induction of electroshock seizures (ES) in rats. We used 113 Wistar rats weighing 250-350g. Under anesthesia, we performed implantation of ears electrodes for the induction of ES and catheterization of the femoral vessels to allow cardiovascular recordings. Measures of mean arterial pressure (MAP) and heart rate (HR) were made before and after 0.3, 2, 5, 10, 15, 20, 25 and 30 minutes post-ES in awaked animals. Respiratory rate (RR), tidal volume (VT) and pulmonary ventilation (Vmin) were evaluated before and after the induction of ES, using the technique of whole-body plethysmographic chamber. The autonomic components were assessed by blockade of β1-adrenoceptors with atenolol and muscarinic colinoceptors with methyl-atropine. The cardiovascular reflexes were assessed by injection of potassium cyanide (KCN) (chemoreflex); fenilbiguanide (FBG) (Bezold-Jarisch reflex) and sodium nitroprusside and phenylephrine (baroreflex). The effects of sino-aortic denervation (SAD) and peripheral adrenergic blockade with atenolol and prazosin (α1-adrenergic antagonist) on responses to induction of ES were also evaluated. The results showed a significant increase in MAP at 0.3 and 2 minutes postES (134 ± 6 and 123 ± 5 mmHg, respectively) compared to control values pre-ES (100 ± 2 mmHg). There were no significant differences among other moments. For baseline HR, compared to control values pre-ES (392 ± 8 bpm) a significant reduction was observed (p<0.01) at 0.3 minutes after electroshock. A significant reversal of HR was observed after 15 (446 ± 13 bpm), 20 (454 ± 10 bpm), 25 (470 ± 7 bpm) and 30 (477 ± 7 bpm) minutes post-ES compared to control values. Regarding the autonomic components (sympathetic and parasympathetic) we observed that the ES caused a significant increase in parasympathetic activity during the post-ictal period (1 minute), followed by a progressive attenuation of this component at 2, 5, 10, 20 and 30 minutes post -ES. In relation to the sympathetic component, we initially observed a progressive increase since from one minute after the ES, which was statistically significant at 5 (17 ± 2* bpm), 10 (26 ± 5** bpm) 20 (34 ± 6** bpm) and 30 (45 ± 6** bpm) minutes after the electroshock when compared to the first minute (-2 ± 2 bpm). After double blockade with atenolol and methyl-atropine, we observed significant increase (p<0.01) in the MAP values after 1 (156 ± 2 mmHg) and 2 (135 ± 6 mmHg) minutes after ES when compared to control values (97 ± 4 mmHg). There was no significant difference among the MAP values at 5, 10, 20 and 30 minutes after the ES and control values. Regarding the respiratory parameters, it was observed apnea during ictal and post-ictal periods in 78% of animals. In addition, there was significant increase of the VT values (p<0.01) at 0.3 (11.4 ± 0.6) and 2 (12.2 ± 0.8) minutes after ES compared to the control (7.1 ± 0.3). In relation to the RR, there was a significant reduction (p<0.01) at 0.3 minutes (67 ± 3 cam) compared to control (97 ± 6 cam). In the same way, in relation to Vmin we observed a significant increase (p<0.01) only at 2 minutes after the induction ES (1249 ± 120) compared to the control (677 ± 36). To the chemoreflex, we observed that KCN produced pressor responses (48 ± 3 mmHg), which was significantly reduced after the induction of ES at 1 (33 ± 4 mmHg) and 5 (34 ± 4 mmHg) minutes compared to control (48 ± 3 mmHg). There was no statistical difference among the other moments after the ES. With regard to HR chemoreflex, there was significant reduction in the first minute post-ES (-106 ± 9 bpm) when compared to control (-194 ± 11 bpm), however, this response was significantly higher compared to control group at 5 (- 263 ± 13 bpm), 10 (-262 ± 16 bpm), 20 (-274 ± 16 bpm) 30 (-253 ± 16 bpm) minutes after the induction of ES. With regard to the Bezold-Jarisch reflex, it was observed initially that the injection of FBG produced hypotensive (-48 ± 2 mmHg) and 22 bradycardic (-248 ± 11 bpm) responses. These hypotensive responses were not statistically different from the control after the induction of ES. In relation to bradycardic response, we observed a significant attenuation in the first minutes after the ES, i.e., at 0.3 (-157 ± 16 bpm) and 2 (-110 ± 16 bpm) minutes when compared to control values (- 248 ± 11 bpm). There were no significant differences in the remaining moments after the ES. Regarding the baroreflex, we observed that only the gain measured in response to bradycardia phenylephrine-induced for 2 minutes after induction of ES was significantly attenuated. After SAD, there was significant attenuation of the bradycardic response induced by ES, which was also observed in the group submitted to blockade with atenolol+prazosin. The results of this study suggest that the tonic-clonic seizures induced by electroshock produced major changes in the: a) cardiovascular system, characterized by hypertensive and bradycardic responses, b) respiratory system, characterized by apnea, hyperpnea and bradypnea observed immediately after induction of ES, c) a significant impairment of the cardiovascular reflexes responses (chemoreflex, BezoldJarisch reflex and baroreflex), d) autonomic dysfunctions observed in the ictal period, in which we observed a significant increase of the cardio-vagal and sympathetic vascular autonomic activities. In the post-ictal period, only an increased cardiac sympathetic activity was observed. Thus, at least in part, this cardio-vagal response is mediated by arterial baroreceptors.
Avaliação da circunferência da cintura como variável preditora de risco coronariano em estudo de base populacional
(Universidade Federal do Espírito Santo, 2008-12-19) Goncalves, Christine Pereira; Mill, José Geraldo; Benseñor , Isabela Judith Martins; Sichieri, Rosely; Rodrigues, Sérgio Lamêgo
INTRODUCTION: Coronary heart disease is one of the most prevalent disease in Brazil and it determines high morbidity and mortality rates. Simple and practical measure that can be used to the health professionals to detect subjects with high risk of coronary heart disease development can be important for its prevention and early diagnostic. In the last years, attention has been given to the rule of abdominal obesity in the development of chronic diseases, especially of the cardiovascular disease. In practice, direct assessment of fat amount is difficult. Therefore, waist circumference can be used as an anthropometric indicator of abdominal adiposity. OBJECTIVES: To evaluate the association between waist circumference and coronary risk factors; to analyze the WHO waist circumference cut-off point capacity to predict these risk factors; to determine the best waist circumference cut-off point to predict hypertension, diabetes, dyslipidemia and high coronary risk in the study sample. METHODS: This is a population-based, cross-sectional study carried out in Vitória city, with 1,662 subjects. Data collect was done using structured questionnaire. Anthropometric data, arterial blood pressure measurements and blood biochemistry data were also collected. Coronary risk was calculated using Framingham score. It was considerated high as it was greater than 20%. WHO waist circumference cut-off points were used as reference. Correlation analyzis, linear and logistic regression were carried out. ROC curve construction using the waist circumference as predictor variable for the coronary risk factors was done. The best waist circumference cut-off point was determined by the Youden index. RESULTS: 764 men and 898 women aged 25 to 64 years were studied. Correlation and regression analyses showed positive association between waist circumference and hypertension, diabetes, dyslipidemia or high coronary risk. In men, the waist circumference cut-off point recommended by WHO presented low or moderate sensitivity to detect the studied risk factors. In women, the perfomance of the point corresponding to 80 cm was moderate to good. Area under the ROC curve was greater than 0.5 for all risk factors. This shows that the waist circumference is able to identify hypertensive, dyslipidemic, diabetic and high coronary risk subjects. Data of this study suggest waist circumference cut-off points between 85 and 95 cm in men and between 76 and 90 cm in women to identify hypertension, dyslipidemia, diabetes and high coronary risk to be used in population with similar characteristics of this study. CONCLUSION: Waist circumference can be used as predictor of hypertension, dyslipidemia, diabetes and high coronary risk. Because it is a simple and practical measure and for it has easy interpretation, it is proposed that waist circumference can be used as a tool of epidemilogical vigilance for these outcomes.
AVALIAÇÃO DA EXPOSIÇÃO AO TRIBUTILESTANHO NOS PARÂMETROS MORFOLÓGICOS E METABÓLICOS EM RATOS EXPOSTOS AO FRIO
(Universidade Federal do Espírito Santo, 2022-06-30) Merlo, Eduardo; Graceli, Jones Bernardes; https://orcid.org/0000000193494369; http://lattes.cnpq.br/3803670746263603; https://orcid.org/0000-0003-0155-1472; http://lattes.cnpq.br/; Rodrigues, Livia Carla de Melo; https://orcid.org/; http://lattes.cnpq.br/2084216553746326; Alves, Leandro Miranda; https://orcid.org/0000-0001-7832-8717; http://lattes.cnpq.br/9883547704448526; Santos, Roger Lyrio dos; https://orcid.org/0000-0003-4316-7196; http://lattes.cnpq.br/1122196233280741; Lima, Leandro Ceotto Freitas; https://orcid.org/0000-0001-9550-6095
Tributyltin (TBT) chloride is an endocrine-disrupting chemical linked with several metabolic complications. Brown adipose tissue (BAT) is emerging as a therapeutic target for metabolic complications. However, few studies have evaluated the TBT effect on BAT function. This study assessed whether a TBT exposure (100 ng/kg/day for 15 days via gavage) could modulate BAT morphophysiology. We evaluated the BAT parameters at room temperature (23ºC) and after a cold tolerance test (CTT – 6ºC) conditions. Interestingly, were observed low T4 levels in TBT rats under normal temperatures. A reduction in body temperature was observed in both conditions in TBT rats, suggesting an abnormal thermogenic function. BAT morphology irregularities were observed in TBT rats. Specifically, an increase in BAT lipid accumulation and unilocular adipocyte number. TBT also reduced lipid droplets and multilocular adipocyte number at room temperature. All these parameters were opposite in the CTT condition. Inflammation signals were observed in the TBT BAT. Collagen accumulation in TAM increased in the ambient condition, exacerbating in the cold condition in TBT rats. ROS production increased under both conditions. Finally, we observed negative correlations between body temperature and BAT lipid accumulation, BAT lipid accumulation and T4 levels, and multilocular adipocyte number. Conversely, and positive correlation was observed between BAT lipid accumulation, inflammation, and ROS production. Thus, these data suggest that the subacute and low dose of TBT exposure impaired BAT morphophysiology linked with lipid accumulation, inflammation, fibrosis, and oxidative stress in male rats.
Avaliação da participação da Na+K+ - ATPase e dos canais para K+ na reatividade de anéis isolados de aorta de ratos após infarto agudo do miocárdio
(Universidade Federal do Espírito Santo, 2011-10-18) Dias, Fernanda Moura Vargas; Stefanon, Ivanita; Vassallo, Dalton Valentim; Bendhack, Lusiane Maria; Mill, José Geraldo; Pereira, Fausto Edmundo Lima
Introduction: Na+K + -ATPase and K + channels are essential for the regulation of membrane potential in the vascular smooth muscle cells (VSMC). The activation or inhibition of these channels by neural, humoral and local vasoactive factors enable the physiological modulation of vascular tone. Studies show that the genesis of changes in vascular reactivity found in diseases such as hypertension and diabetes may be related to increased oxidative stress and alteration of NO bioavailability that influence the Na+K + -ATPase and K + channels of the VSM . Although several studies demonstrate changes in vascular reactivity after myocardial infarction (MI), no study to date evaluated the involvement of Na+K + -ATPase and K + channels in the alterations of vascular reactivity that occur in a chronic phase after MI, in rats with similar scar area (SA), with and without signs of heart failure (HF). Objective: To evaluate the functional activity of the Na+-K + -ATPase ouabain (OUA)-sensitive and K + channels in aortic rings of rats, after MI, with similar SA, with and without signs of HF. Materials and Methods: 89 male Wistar rats (220-360 g) were divided into: Sham operation (Sham, n = 37), animals after MI without signs of HF (Inf, n = 27) with signs of HF (HF, n = 25). The MI was surgically induced by occlusion of the left anterior coronary artery. 30 days after MI, animals were weighed, anesthetized (urethane, 1.2 g / kg, ip), catheterized and hemodynamic measurements were performed. The animals were sacrificed and the mass data were evaluated by the ratio of wet mass of the right ventricle (RV/BW), left ventricle (LV/BW) and lung (Lung/BW) by body mass (BW) of each animal. The aortic rings were removed, superfused with Krebs solution and aerated with carbogen mixture. The functional activity of the Na+-K + - ATPase OUA-sensitive was investigated by the relaxation induced by potassium (0- 10 mM) before and after OUA incubation, in rings with intact (E+) and removed endothelium (E-), and after L-NAME incubation. The participation of K+ channels in vascular reactivity was performed using the acetylcholine (ACh) induced relaxation after L-NAME and K+ channels blockers incubation: tetra-ethylammonium (TEA, nonselective blockers of K+ channels), Aminopiridin (4-AP, voltage-dependent K+ channels inhibitor - Kv), Iberiotoxin (blocker of Ca2+ channels sensitive of largeconductance - BKCa), Apamina (blocker of Ca2+ channels sensitive of smallconductance - SKCa) and the association of iberiotoxin and apamin. We performed the evaluation of α1 Na+-K + -ATPase and eNOS protein expression by Western blot. The production of superoxide anion (O2 .- ) "in situ" was performed by the fluorescence produced by oxidation of dihidroethidium (DHE). The SA was assessed by counting of the points on graph paper (planimetry) and histology with picrosirius red staining. We carried out evaluation of sensitivity (pEC50) and maximal response (Rmax) to ACh induced relaxation. To compare results between groups was performed ANOVA 1 and 2 ways, post hoc tests Tukey, Bonfferroni and Student t. Values were considered significant for *P < 0.05. The experimental protocols were approved (005/2007) by the Ethics Committee on Animal Use (CEUA-EMESCAM). Results: There were no differences between the SA (Inf: 33.67 ± 1.62, HF: 38.7 ± 2.45%), body mass (Sham: 322 ± 7; Inf: 341 ± 5, HF: 337 ± 7 g) and the ratio LV/BW (Sham: 2.12 ± 0.03; Inf: 2.19 ± 0.05, IC: 2.27 ± 0.07 mg/ g) between groups. However, there were increased in the RV/BW (Sham: 0.64 ± 0.09; Inf: 0.74 ± 0.04, HF: 1.25 ± 0.08*+ mg/g; *+P <0.01), Lung/BW (Sham: 4.41 ± 0.35, Inf: 3.91 ± 0.48, HF: 8.34 ± 0.69*+ mg/ g *+P< 0.01) and LVEDP (Sham: 5.26 ± 0.52, Inf: 7.20 ± 0.64, IC: 19.65 ± 2.13*+ ; *+P < 0.05) in the IC group when compared with Sham and Inf. The K + -induced relaxation was higher in Inf compared to Sham and HF animals. However, the endothelium removal, as well as the L-NAME or TEA incubation were able to abolish the differences between groups. In IC group K + -induced relaxation was increased in the presence of OUA compared with Sham. Removal of the endothelium and incubation with TEA were able to abolish the differences between the Sham and HF groups, but the LNAME incubation did not. In the HF group compared with Sham and Inf, L-NAME incubation decreased the K + -induced relaxation. After incubation with TEA, Rmax and the sensitivity of aortic rings to ACh Inf and HF decreased compared with Sham. The dAUC performed with the curves of ACh before and after incubation with 4-AP was higher in Inf animals compared with Sham and HF. Although the blocking with Apamin or Iberiotoxin has not caused the differences between the dAUC of groups, the double block resulted in the dAUC higher in HF group compared with Sham and Inf. There was no difference in protein expression of α1 Na+K + -ATPase between groups. However, the α1 Na+-K + -ATPase, p-eNOS and eNOS protein expression was diminished in the HF animals. In addition, a higher production of O2 .- in the Inf group compared with Sham and HF. Conclusions: In a chronic phase after experimental MI in rats with similar AI, with and without signs of HF, differences exist in mechanisms that induce vascular relaxation characterization of two distinct groups with functional responses. Among the mechanisms involved are increasing the participation of K+ channels and oxidative stress after MI, as well as decreased expression of eNOS and p-eNOS in the HF group of animals. Moreover, it is suggested that the Inf animals Kv channels are contributing more to the vascular relaxation, while the HF animals, seem to depend on the channels of KCa. Differences in vascular relaxation, according to the protocols used in this study, no relation to the change in function and expression of Na+K +- ATPase between the groups.
Avaliação de marcadores de remodelamento cardíaco (funcionais, bioquímicos e estruturais) em ratos submetidos a exercício resistido e tratamento com decanoato de nandrolona.
(Universidade Federal do Espírito Santo, 2015-07-13) Lima, Ewelyne Miranda de; Orientador1; https://orcid.org/; http://lattes.cnpq.br/; Andrade, Tadeu Uggere de; Sampaio, Karla Nívea; Gouvêa, Sônia Alves; Campagnaro, Bianca Prandi
Resistance training (RT) has often been associated with the abuse of anabolic androgenic steroids (AAS) by athletes and non-athletes. The aim of this study was to evaluate the effects of resistance training (RT) with or without nandrolone decanoate, with the levels of cytokines and activity of angiotensin-converting enzyme (ACE) in the heart, and the sensitivity of cardiopulmonary Bezold-Jarisch reflex (BJR). Male Wistar rats were divided into 3 groups: C (receiving vehicle, untrained); E (RT: after one week of adaptation water, rats were trained to jump into the water twice a week for 4 weeks), DN (treated with nandrolone decanoate 10 mg kg twice a week, intramuscularly) e DNE (treated with nandrolone decanoate 10 mg kg twice a week, intramuscularly, associated with RT). The BJR was analyzed by measuring bradycardic and hypotensive responses induced by administration in bolus of five serotonin randomized doses (2 to 32 g/kg body weight). Myocyte hypertrophy and collagen deposition in the matrix was determined by morphometric analysis of images from slides stained with H&E and picrosirius red respectively. The TNF-α levels in the heart and ACE activity was determined by Elisa assay. The RT promoted resting bradycardia in E group (bpm 312 ± 9, p <0.01) when compared with C group (360 ± 11 bpm) and ND did not influence this parameter NDE (bpm 324 ± 9, p <0.05), furthermore promoted physiological hypertrophy in myocytes without collagen deposition and no other changes were observed. The ND association with RT shown myocyte hypertrophy, type I collagen deposition, increase on TNF-α levels (C: 207 ± 9; E: 211 ± 8; DN: 269 ± 10; DNE: 242 ± 10 pg / mg, p <0,01) and ACE activity(C: 27,0 ± 7 ; E: 39,0 ± 6; DN: 50 ± 5; DNE: 65,0 ± 4 %, p <0,01), decreased IL-10 levels (C: 220 ± 7; E: 231 ± 5; DN: 165 ± 5; DNE: 164 ± 4 pg / mg, p<0,01), impairment in the sensitivity of BJR and hypertension(C: 104 ± 2 mmHg; E: 108 ± 8 mmHg; DN: 144 ± 7; DNE: 138 ± 5 mmHg; p <0,01). ND is associated with changes in cardiac structure and function as a result of the development of pathological cardiac hypertrophy (cytokine imbalance in heart elevation of ACE activity) and cardiac injury, and resistance training was unable to reverse the deleterious cardiovascular effects.
Avaliação de novas vias de disfunção endotelial no modelo experimental de hipertensão essencial: ações benéficas da inibição da fosfodiesterase-5
(Universidade Federal do Espírito Santo, 2019-06-21) Leal, Marcos Andre Soares; Vasquez, Elisardo Corral; https://orcid.org/0000-0001-7712-7454; http://lattes.cnpq.br/0588347232578369; https://orcid.org/; http://lattes.cnpq.br/; Bissoli, Nazare Souza; https://orcid.org/0000-0002-3456-2437; http://lattes.cnpq.br/8865368585732583; Nogueira, Breno Valentim; https://orcid.org/0000000221990635; http://lattes.cnpq.br/0011229320439147; Balarini, Camille de Moura; https://orcid.org/; http://lattes.cnpq.br/0891042053942023; Barauna, Valerio Garrone; https://orcid.org/0000000328320922; http://lattes.cnpq.br/1583882564447423
Arterial hypertension is a condition associated with endothelial dysfunction of small and large vessels, accompanied by an imbalance in the production of reactive oxygen species (ROS), vasodilators and vasoconstrictors prostanoids and NO. The aim of this study was to investigate the effects of sildenafil, a selective phosphodiesterase-5 inhibitor that increase NO pathway, on endothelial function in aortas from Spontaneously Hypertensive Rats (SHR). EXPERIMENTAL APPROACH: SHR treated with sildenafil (40 mg/kg/day, p.o., 3 weeks) were compared to untreated SHR and Wistar control rats. Vascular reactivity was measured in isolated rat aortic rings. Circulating endothelial progenitor cells and superoxide anions were measured by flow cytometry. Plasmatic total antioxidant capacity, NO production and aorta lipid peroxidation were determined by spectrophotometry. Picrosirius staining and scanning electron microscopy was used for vascular morphology and structural analysis of the endothelial surface. KEY RESULTS: Sildenafil partially restored the vasodilator response to acetylcholine in SHR aorta and normalized the vasoconstrictor response to phenylephrine. Our experiments with a NO synthase blocker revealed an augmented participation of NO, decreased participation of oxidative stress, prostanoids Cox-1-derived in the vascular dilation and contration, respectively, in sildenafil-treated SHR and improvement in prostacyclin thromboxane balance. The improved vascular function in sildenafil treated SHR was unaffected by SC-560 and apocynin.The relaxant responses to sildenafil and 8-Br-cGMP were normalized in sildenafil-treated SHR. Sildenafil restored the prooxidant/antioxidant balance and the vascular morphology and endothelial architecture. CONCLUSIONS AND IMPLICATIONS: Sildenafil reverses endothelial dysfunction in SHR by improving vascular contraction and relaxation to phenylephrine and acetylcholine, respectively. The mains mechanism behinde sildenafil effects are reduction of the oxidative stress and cyclooxygenase-1 prostanoids, improvement in prostacyclin thromboxane balance, with an augmentation of NO bioavailability and improvement in the cGMP/PKG signaling. Also, sildenafil improves structural damage in the vascular and endothelium surface.
Avaliação do efeito protetor do extrato hidroalcoólico de eugenia uniflora na lesão renal aguda experimental
(Universidade Federal do Espírito Santo, 2017-12-20) Meira, Eduardo Frizzera; Gava, Ágata Lages; Lyrio, Roger; Santos, Leonardo dos; Valentim, Breno; Campagnaro, Bianca Prandi
Acute kidney injury (AKI) is characterized by a rapid and potentially reversible decline in renal function; however, the current treatment of AKI is not specific and is associated with limited supportive care. Considering the need for new therapeutic approaches, we believe that the hydroalcoholic extract of leaves of Eugenia uniflora (pitanga) because of its antioxidant properties, may be beneficial for the treatment of RAI induced by renal ischemia / reperfusion (I / R). Hydroalcoholic extract from Eugenia uniflora leaves (200mg / kg, oral) or vehicle (0.9% saline) was administered to Wistar rats prior to the induction of bilateral renal ischemia (45 minutes). After 24 hours of reperfusion, clearances of inulin and paraminothiazurate were performed to determine the glomerular filtration rate (GFR), renal plasma flow (RPF), renal blood flow (RBF) and renal vascular resistance (RVR). The production of superoxide anion, hydrogen peroxide, peroxynitrite, hydroxyl radical, activity of oxidant enzymes and antioxidants and apoptosis in the kidneys were evaluated by flow cytometry. Evaluations of the expression of the antioxidant enzymes were performed by the Western blot technique. I / R resulted in reduced TFG, FPR and FSR and increased RVR, but these parameters were improved in rats receiving the extract. Treatment with Eugenia uniflora extract resulted in a decrease in oxidative stress and an increase in the activity and expression of antioxidant enzymes and a decrease in apoptosis in the kidneys of rats submitted to I / R. Our data showed that the hydroalcoholic extract of leaves of Eugenia uniflora may be able to prevent or attenuate the loss of renal function induced by ischemia reperfusion through the reduction of oxidative stress and apoptosis, thus providing valuable information that may subsidize the incorporation of herbal medicines into SUS.
Avaliação do polimorfismo de receptores adrenérgicos na hiper-reatividade cardiovascular de testes estressores
(Universidade Federal do Espírito Santo, 2011-06-17) Simões, Giovana Machado Souza; Kuniyoshi ,Fátima Helena Sert; Vasquez, Elisardo Corral; Trombetta, Ivani Credidio; Errera , Flávia Imbroisi Valle; Stefanon,Ivanita; Mill , José Geraldo
Background: In Brazil, the cardiovascular disease are the main cause of morbimortality, being responsible for 27,4% of the deaths caused for illnesses of cardiovascular origin (Health department, 2007; VI Brazilian Lines of direction of Arterial Hypertension, 2010). In recent study epidemiologist carried through in our city (Project MONICA) it was verified that 37% of the individuals in the band of 18 the 64 years of age were carrying of systemic arterial hypertension (Molina, 2002). The precocious detention of familiar antecedents for the cardiovascular disease allows the evaluation of its development as well as application of prophylactic measures, being late or until preventing the installation of injuries in agency-target. Therefore, our study it aims at to verify the association of the polymorphism of the beta2 and alpha1- adrenergics receptor with exaggerated the pressor and cardiac output reply during the laboratorial stress tests, in normotenses individuals. As well as, to correlate the hemodynamic responses with the sort and history of familiar antecedents of the stress tests Methods: The enlisted 98 volunteers of both (50mulheres/48 men), in the etária band of 20 the 55 years. Obeying the criteria of inclusion and authorization written for the TCLE, they had been gotten measured of the weight corporal (kg), height (m) and calculated the index of Corporal Mass (IMC=peso/altura2). Being excluded voluntary with cardiac disease associates, diabetes mellitus and obesity (IMC>30 Kg/m2). Collection of samples of peripheral venous blood of jejum of 8 hours was carried through, for evaluation biochemist (glicemia of jejum, total cholesterol and fractions, triglicérides) and for the extration of the DNA, in order to determine the polymorphism for analysis of restriction of polymorphism fragmentos (RFLP), extration of DNA, followed of amplification for Polymerase Chain Reaction (PCR) for polimorfos Arg16Gly, Gln27Glu and Arg492Cys, digestion of the amplified product, with genotipagem in the gel of acrilamida 10%. Carried through measured of accidental Pará, followed of the application of the test of Handgrip, color Stroop test and pressor Cold. As analysis statistics, test t of student for independent samples was used. In the not-parametric analysis of categorical 0 variable, these had been compared using the qui-square, including the test of comparison of ratio. The differences between two samples had been considered significant when p<0.05. The test of Hardy-Weinberg was carried through to get the alélicas frequencies and genotypc and to verify if the studied population it is in genetic balance. Followed of the analysis of the disequilibrium of linking, manual way and later confirmed through software Arlequin 3,11 (freeware) for analysis of data of population genetics.

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