Search

Submitted by Boris Flegr (boris@uerj.br) on 2021-01-05T19:35:52Z No. of bitstreams: 1 TESE_FINAL_PUBLICADA_Valeria_Verri.pdf: 4317247 bytes, checksum: 77857457139cc02cad02f3d4551edd7d (MD5) Made available in DSpace on 2021-01-05T19:35:52Z (GMT). No. of bitstreams: 1 TESE_FINAL_PUBLICADA_Valeria_Verri.pdf: 4317247 bytes, checksum: 77857457139cc02cad02f3d4551edd7d (MD5) Previous issue date: 2019-09-23 Erectile dysfunction (ED) of vascular etiology is a highly prevalence health problem and is directly related to an increased cardiovascular risk. Phosphodiesterase type 5 inhibitors in addition to treating ED, as they have the property of increasing the bioavailability of nitric oxide, they could be promising for the treatment of systemic hypertension and to improve vascular endothelial function. The primary aim of this study was to evaluate the acute and chronic effect of sildenafil citrate (SIL) on systemic and penile microvascular endothelium function and systemic arterial pressure in primary arterial hypertension patients with ED. This is a prospective, randomized, double-blind, placebo-controlled, cross-over study. A total of 57 hypertensive men, with erectile dysfunction, aged 57.7±5.8 years and 50 age-matched normotensive subjects were included. The Simplified International Index of Erectile Function (IIEF-5) was used to evaluate erectile function. The evaluation of forearm and penile microvascular endothelial function was performed using laser speckle contrast imaging (LSCI), coupled with acetylcholine (ACh) iontophoresis. All volunteers were evaluated by LSCI before and 1 h after oral administration of SIL 100 mg. Later, only the hypertensive patients were randomized to investigate the chronic effect of SIL. They were treated for four weeks with SIL 50 mg twice daily or placebo, in two steps, with a 30-day washout period between treatments. The blood pressure values recorded at each treatment step was performed through 24 h ambulatory blood pressure monitoring (ABPM). Hypertensive patients had significantly higher mean values of anthropometric and laboratory variables than normotensive individuals. After SIL 100 mg mean arterial pressure fell -4.6±8.3 mmHg in normotensive and -8.2±14.6 mmHg in hypertensive patients. There was a significant increase in basal cutaneous vascular conductance (CVC) values, CVC peak values and in the area under the curve (ASC) of penile microvascular vasodilation of both normotensive and hypertensive patients (P=0.002, P=0.0001 and P=0.001) and (P

Submitted by Boris Flegr (boris@uerj.br) on 2021-01-05T18:49:52Z No. of bitstreams: 1 Gabriella de Oliveira Lopes_Dissertacao.pdf: 2471705 bytes, checksum: f4cae6409e485d8e1e2442b79bd592de (MD5) Made available in DSpace on 2021-01-05T18:49:52Z (GMT). No. of bitstreams: 1 Gabriella de Oliveira Lopes_Dissertacao.pdf: 2471705 bytes, checksum: f4cae6409e485d8e1e2442b79bd592de (MD5) Previous issue date: 2019-03-13 Introduction: Studies assessing the vascular function and redox status of people living with HIV in response to exercise training are scarce. Objective: To compare macro- and microvascular endothelial function in physically active vs. inactive HIV-infected patients under antiretroviral therapy. Methods: Using a cross-sectional design, 19 patients with HIV (53.1 ± 6.1 yr) physically active (60 min/session; 3 sessions/wk; moderate intensity) and 25 inactive (51.2 ± 6.3 yr) were compared as for macro- and microvascular reactivity, systemic microvascular density, and oxidative stress. Results: Active patients showed greater increment of forearm blood flow during reactive hyperemia (521.7±241.9 vs. 361.4±125.0 %; P=0.04) and systemic microvascular density (120.8±21.1 vs. 105.6±25.0 capillaries.mm-2; P=0.03) than inactive patients. No significant difference between groups was detected for endothelium-dependent and independent skin microvascular response (P>0.05). As for redox status, carbonyl groups (P=0.22), lipid peroxidation (P=0.86), catalase activity (P=0.99), and nitric oxide levels (P=0.72) were similar across groups. However, superoxide dismutase activity was greater in active vs. inactive HIV (0.118±0.013 vs. 0.111±0.007 UmL-1; P=0.05). Immune function reflected by total T CD4 and T CD8 cells count (cell.mm-3) did not differ between active and inactive groups (P>0.82). Conclusion: Physically active HIV exhibited similar immune function, but greater macrovascular reactivity, systemic microvascular density, and superoxide dismutase activity than inactive patients of similar age. Introdução: São escassos os estudos sobre a função vascular e estado redox de pacientes vivendo com HIV em resposta ao treinamento físico.Objetivo: Comparar a função endotelial micro e macrovascular entre pacientes vivendo com HIV fisicamente ativos e inativos, sob utilização da terapia antirretroviral. Métodos: Através de desenho transversal, 19 pacientes com HIV (53 ± 6 anos) fisicamente ativos (60 min/sessão;3sessões/semana; intensidade moderada) e 25 inativos (51 ± 6 anos) foram comparados quanto a reatividade macro e microvascular, densidade microvascular sistêmica e estresse oxidativo. Resultados: O grupo ativo apresentou maior incremento do fluxo sanguíneo do antebraço durante a hiperemia reativa pós-oclusiva (521,7 ± 241,9 vs. 361,4 ± 125,0%; P = 0,04) e densidade microvascular sistêmica (120,8 ± 21,1 vs. 105,6 ± 25,0 capilares.mm-2; P = 0,03) em relação aos pacientes inativos. Nenhuma diferença significativa entre os grupos foi detectada para a vasodilatação microvascular cutânea endotélio-dependente e independente (P> 0,05). Quanto ao estado redox, grupo carbonila (P = 0,22), peroxidação lipídica (P = 0,86), atividade da catalase (P = 0,99) e níveis de óxido nítrico (P = 0,72) foram similares entre os grupos. No entanto, a atividade da superóxido dismutase foi maior no grupo ativo vs. inativo (0,118 ± 0,013 vs. 0,111 ± 0,007 UmL-1; p = 0,05). A função imune refletida pela contagem total de células T CD4 e T CD8 (cell.mm-3) não diferiu entre os grupos ativo e inativo (P> 0,82). Conclusão: Pacientes com HIV fisicamente ativos exibiram função imunológica similar, mas maior reatividade macrovascular, densidade microvascular sistêmica e atividade da superóxido dismutase em relação a pacientes inativos com idade pareada.

Submitted by Boris INFORMAT (boris@uerj.br) on 2021-04-26T01:11:52Z No. of bitstreams: 1 Anatalia Kutianski Gonzalez Vieira Tese completa.pdf: 2063442 bytes, checksum: 4a1fc4f65e7a9545005e5ce1648e41ba (MD5) Made available in DSpace on 2021-04-26T01:11:52Z (GMT). No. of bitstreams: 1 Anatalia Kutianski Gonzalez Vieira Tese completa.pdf: 2063442 bytes, checksum: 4a1fc4f65e7a9545005e5ce1648e41ba (MD5) Previous issue date: 2016-01-21 Conselho Nacional de Desenvolvimento Científico e Tecnológico The nutritional imbalance at the beginning of life in the period known as critical window, leads to the development of obesity, dyslipidemia, diabetes and cardiovascular disease in adulthood. This study aimed to analyze in male Swiss mice adults at 120 days of life the effects and associations of overnutrition on lactation by reducing litter on hemodynamic parameters, in mitochondrial energy metabolism (respiratory control ratio and oxidation of carbohydrates and fatty acids), in ATP production, in cardiac, hepatic and plasma oxidative stress, in molecular biology by key proteins and collagen deposition in heart. The mice were divided into two groups (control and overfed) subject to two conditions (baseline and ischemia/reperfusion) forming four groups in total: control group baseline (CGBL), control group ischemia/reperfusion (CGIR), overfed group baseline (OGBL) and overfed group ischemia/reperfusion (OGIR). The OG developed increased weight of the left ventricle, central fat and fasting glucose. Plasma levels of insulin and leptin are increased in OG compared to the CG. EDP, Max dP/dt and Min dP/dt parameters showed significant differences in baseline and post-ischemic presenting OGIR an increase of EDP and Min dP/dt and reduce of Max dP / dt compared to OGBL and increase of EDP compared to CGIR. Imbalances in cardiac hemodynamics were associated with mitochondrial dysfunction as observed by the reduction on fatty acid and carbohydrate oxidation and in the RCR to carbohydrate in OG and the reduction in ATP production in OGIR compared to CGIR and OGBL. Furthermore, cardiac hypertrophy markers as ANP is increase in OGIR and BNP in OGBL, increased collagen deposition in OGIR compared to OGBL and GCIR as well as in CGIR compared with CGBL, increased post-ischemia sensitivity in insulin signaling pathway with increased of PTP1B, IRS1 and pAKT2 and reduced pAKT1, AKT2, AMPK, pAMPK and reduced capacity utilization of fatty acids by reducing the content of CD36 and FABP. Finally, it was showed that the degradation of lipids and/or proteins is altered between CG and OG in heart, liver and plasma. The study demonstrates significant consequences of overnutrition on lactation by reducing litter on cardiac hemodynamic, cardiac sensitivity to ischemia and cardiac remodeling due to readjustments on cardiac energy metabolism via changes in insulin signaling pathway, reduction in ATP production and oxidation of energy substrates. O desequilíbrio nutricional no início da vida no período conhecido como janela crítica, leva ao desenvolvimento da obesidade, dislipidemia, diabetes e doenças cardiovasculares na idade adulta. Este estudo teve como objetivo analisar em camundongos machos Swiss adultos aos 120 dias de vida os efeitos e associações da hiperalimentação na lactação por redução de ninhada nos parâmetros hemodinâmicos, no metabolismo energético mitocondrial (razão do controle respiratório e oxidação de carboidratos e ácidos graxos), na produção de ATP, no estresse oxidativo cardíaco, hepático e plasmático, na biologia molecular através de proteínas-chave e na deposição de colágeno cardíaco. Os camundongos foram divididos em dois grupos (controle e hiperalimentado) submetidos a duas condições (linha de base e isquemia/reperfusão) formando quatro grupos no total: grupo controle linha de base (GCLB), grupo controle isquemia/reperfusão (GCIR), grupo hiperalimentado linha de base (GHLB) e o grupo hiperalimentado isquemia/reperfusão (GHIR). O GH desenvolveu maior peso do ventrículo esquerdo, gordura central e glicemia de jejum. Os níveis plasmáticos de insulina e leptina encontram-se aumentados no GH comparado ao GC. Os parâmetros EDP, Max dP/dt e Min dP/dt apresentaram diferenças significativas nas condições basais e pós-isquêmicas apresentando o GHIR aumento da EDP e Min dP/dt e redução da Max dP/dt comparado ao GHLB e aumento da EDP comparado ao GCIR. Os desequilíbrios na função cardíaca foram associados a disfunção mitocondrial, uma vez que se observou redução na oxidação de ácido graxo e carboidrato e, na RCR para carboidrato no GH e a redução na produção de ATP no GHIR comparado ao GCIR e GHLB. Além disso, aumento nos marcadores de hipertrofia cardíaca ANP no GHIR e do BNP no GHLB, aumento na deposição de colágeno no GHIR comparado ao GHLB e GCIR bem como no GCIR comparado com o GCLB, aumento da sensibilidade pós isquemia na via de sinalização da insulina com aumento da PTP1B, IRS1 e pAKT2 bem com redução da pAKT1, AKT2, AMPK, pAMPK, e redução da capacidade de utilização dos ácidos graxos via redução do conteúdo da CD36 e FABP. Finalmente, foi demonstrado que a degradação de lipídios e/ou proteínas se encontra alterada entre os GC e GH a nível cardíaco, hepático e plasmático. O estudo demonstra expressivas consequências da hiperalimentação na lactação por redução de ninhada sobre a função cardíaca, a sensibilidade cardíaca à isquemia e o remodelamento cardíaco em virtude de readaptações no metabolismo energético cardíaco via alterações na via de sinalização de insulina, redução na produção de ATP e oxidação dos substratos energéticos.

Submitted by Boris Flegr (boris@uerj.br) on 2021-01-06T20:53:32Z No. of bitstreams: 1 DIOGO PANAZZOLO 08012014.pdf: 2890437 bytes, checksum: bab15505dbebdb35817c02a326eb4890 (MD5) Made available in DSpace on 2021-01-06T20:53:32Z (GMT). No. of bitstreams: 1 DIOGO PANAZZOLO 08012014.pdf: 2890437 bytes, checksum: bab15505dbebdb35817c02a326eb4890 (MD5) Previous issue date: 2013-12-06 Conselho Nacional de Desenvolvimento Científico e Tecnológico The action that estrogen plays on the endothelium depends on its integrity and consequently on the clinical characteristics of each individual. The use of menopausal hormone therapy (MHT) in women with low cardiovascular risk usually results in beneficial effects, since it is started in a period close to menopause. In contrast, its use often results in harmful effects in women at high cardiovascular risk, such as diabetic ones or those with established atherosclerotic lesions, and even in those that the beginning of MHT exceeds ten years from menopause. Our goal is to evaluate the effects of estrogen on endothelial function in overweight women, ie, individuals at intermediate cardiovascular risk. For this purpose, 44 postmenopausal women, aged 47-55 years with body mass index (BMI) from 27.5 to 34.9 kg / m², were randomized into placebo (P) and transdermal estrogen (TE) groups. The intervention consisted of using transdermal estradiol 1mg per day for a period of three months. Participants underwent endothelial reactivity assessment at rest and after ischemia [by venous occlusion plethysmography (VOP), with assessment of forearm blood flow (FBF) and dynamic nailfold videocapillaroscopy (DNV), with assessment of red blood cell velocity (RBCV)], measurements of soluble adhesion molecules [E-selectin, intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1)], measurement of insulin sensitivity [by homeostatic model assessment of insulin resistance (HOMA-IR) and area under the curve (AUC) of insulin during the oral glucose tolerance test (OGTT)] and measurements of blood and plasma viscosities. The participants aged 51.77 ± 2.3 years, BMI 31.52 ± 2.54 kg/m² and had a time since menopause of 3 [2-5] years. P group showed no significant change in any variable. After intervention, the TE group compared to the baseline presented in DNV lower time taken to reach RBCV during post-occlusive reactive hyperemia (PORH) (4,0 [3,25-5,0] vs. 5,0 [4,0-6,0] s, P

Submitted by Boris Flegr (boris@uerj.br) on 2021-01-06T20:53:12Z No. of bitstreams: 1 Tese_Final_Priscila Alves Maranhao.pdf: 1258682 bytes, checksum: 84ec9b1ac404b329ff94e92fe884e536 (MD5) Made available in DSpace on 2021-01-06T20:53:12Z (GMT). No. of bitstreams: 1 Tese_Final_Priscila Alves Maranhao.pdf: 1258682 bytes, checksum: 84ec9b1ac404b329ff94e92fe884e536 (MD5) Previous issue date: 2013-04-24 Fundação Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro Changes in eating habits have caused striking effects on public health, directly related to increased intake of food rich in fat, mainly saturated fat. The main consequence of this consumption is the excessive and prolonged state of postprandial lipemia (PPL), considered one an important factor related to metabolic abnormalities and vascular damage. The aim of this study was to assess effects of fat overload on microvascular reactivity in obese women. Of the 41 study participants, 21 had the diagnosis of obesity, with BMI of 32.4 ± 1.6 kg/m2 (mean ± SD) and age of 31.6 ± 5 years and 20 healthy women with BMI of 21.9 ± 1.7 kg/m2and age 27.2 ± 5.5 years. After clinical and laboratorial assessment, participants had the microcirculation examined by two methods: dynamic, using the nailfold bed to assess functional capillary density (FCD), red blood cell velocity in in control conditions (RBCV) and peak (RBCVmax) and time (TRBCVmax) to reach it after 1 min arterial occlusion. The second technique was the finger dorsum to assess FCD at rest and during the reactive hyperemia response and after venous occlusion. Blood sampling was performed to determine total cholesterol (TC), triglycerides (TG), HDL- c and free fatty acids (FFA), glucose, insulin and plasma viscosity at 30 and 50 rotations per minute (rpm). Systolic (SBP) and diastolic (DBP) blood pressures and heart rate (HR) were also measured. After these measurements at rest, all participants received a meal rich in lipids, and after 30, 60, 120 and 180 min after ingestion, videocapillaroscopy exams and blood samples were taken again. Results - Obese participants, after fat overload, presented significantly lower values than at rest at finger dorsum of FCD (p = 0.02), FCD during reactive hyperemia (p = 0.02) and post- venous occlusion (p = 0.02), HDL-C (p

Submitted by Boris Flegr (boris@uerj.br) on 2021-01-06T20:53:58Z No. of bitstreams: 1 Guilherme Loures de Araujo Penna Tese completa.PDF: 6584503 bytes, checksum: 50af8eaf1ccf9aa14208ddb504b93644 (MD5) Made available in DSpace on 2021-01-06T20:53:58Z (GMT). No. of bitstreams: 1 Guilherme Loures de Araujo Penna Tese completa.PDF: 6584503 bytes, checksum: 50af8eaf1ccf9aa14208ddb504b93644 (MD5) Previous issue date: 2013-03-06 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Over the past few years, despite all research and development, mortality from sepsis remains high. In microcirculatory studies using experimental models of sepsis, and invasive techniques, significant reduction in functional capillary density were observed. The recently developed technique called sidestream dark field (SDF) imaging, allows transcutaneously evaluation of the microcirculation. This technique has demonstrated reduction on functional capillary density in patients with severe sepsis, when compared to healthy individuals. Subsequently, it was shown that even in septic patients with stabilized vital signs, persistent alterations in the microcirculation are associated with worse prognosis. Obviously, patients with severe sepsis or septic shock suffer a lot of therapeutic interventions, many of them affecting the microvasculature. Studies analyzing the microcirculation in patients using nitroglycerin, corticosteroids, receiving blood transfusion or infusion of norepinephrine were recently published. However, to date, no publications have described the influence of sedatives in the microcirculation of these patients. The most commonly drugs used for sedation of mechanically ventilated patients are midazolam and propofol. The main objectives of this study were to observe the effects of two sedative agents used in clinical practice in the microcirculation of patients with septic shock. The sidestream dark field imaging technique was used to compare the effects on microcirculation of midazolam with propofol in patients with septic shock and verify a relationship between microcirculatory changes caused by sedatives and different variations of hemodynamic parameters such as blood pressure, heart rate, lactate and central venous oxygen saturation.We have prospectively studied 16 patients admitted to the Intensive Care Unit of Casa de Saúde São José. Patients admitted with a diagnosis of septic shock and in need of mechanical ventilation were submitted to microcirculation analysis in the sublingual mucosa using sidestream dark field imaging technique. These patients were sedated according to the sedation protocol, initially with propofol, and later on with midazolam. The main results were: the macrohemodynamics did not differ during the two moments of examination; BIS (bispectral index of sedation) remained in the range recommended during both exams and increased when patients woke up, as expected, and finally, the proportion of small vessels perfused and microcirculatory flow index were significantly lower, while the heterogeneity index was higher, when patients were receiving propofol infusion in comparison with the midazolam one. We concluded that in patients with septic shock, midazolam administration results in an improvement of the microcirculation when compared with the administration of propofol and this difference could not be attributed to changes in systemic hemodynamic. Ao longo dos últimos anos, apesar de todo desenvolvimento e pesquisa, a mortalidade na sepse permanece elevada. Na área de microcirculação foram realizados estudos em modelos experimentais de sepse ao longo das últimas duas décadas, quando se observou, através de técnicas invasivas, alterações como redução expressiva da densidade capilar funcional. A técnica denominada sidestream dark field (SDF) imaging, recentemente desenvolvida, permite a avaliação da microcirculação de forma transcutânea. A utilização desta técnica permitiu evidenciar a redução da densidade capilar funcional em pacientes com sepse grave quando comparado a um indivíduo saudável. Posteriormente, foi demonstrado que alterações persistentes na microcirculação de pacientes sépticos, mesmo com sinais vitais estabilizados, estão associadas com pior prognóstico.Evidentemente, os pacientes com sepse grave ou choque séptico sofrem uma grande quantidade de intervenções terapêuticas, aonde muitas delas alteram a microcirculação. Estudos analisando a microcirculação em pacientes em uso de nitroglicerina, corticóide, recebendo hemotransfusão ou ainda infusão de noradrenalina foram publicados recentemente.Entretanto, até o presente momento, não existem publicações que descrevam a influência dos sedativos na microcirculação de pacientes com choque séptico. As drogas mais comumente utilizadas para sedação de pacientes em ventilação mecânica são o sedativo midazolam e o anestésico propofol. Os objetivos do estudo foram: avaliar o efeito dos principais agentes sedativos utilizados na prática clínica na microcirculação de pacientes com choque séptico utilizando a técnica de sidestream dark field imaging, comparar os efeitos na microcirculação do midazolam com o propofol em pacientes com choque séptico e verificar se existe relação das alterações microcirculatórias provocadas pelos sedativos com as variações de diferentes parâmetros hemodinâmicos, gasométricos ou metabólicos como pressão arterial, índice cardíaco, lactato e saturação venosa central de oxigênio. Foram estudados (estudo prospectivo) 16 pacientes internados no Centro de Terapia Intensiva da Casa de Saúde São José. Os pacientes internados com diagnóstico de choque séptico e que possuíam indicação clínica de ventilação mecânica e de suspensão diária da sedação foram submetidos ao estudo da microcirculação na mucosa sublingual utilizando a técnica de sidestream dark field imaging. Estes pacientes foram sedados conforme orientação do protocolo já existente de sedação, inicialmente com propofol e posteriormente com midazolam. Os principais resultados observados foram:a macrohemodinâmica não diferiu nos 2 momentos do exame, o BIS (bispectral índex of sedation) se manteve na faixa recomendada nos 2 momentos do exame, tendo aumentado quando o paciente acordava, conforme esperado, e a proporção de vasos pequenos perfundidos e o índice de fluxo da microcirculação foram significativamente menores, enquanto o índice de heterogeneidade foi significativamente maior quando os pacientes estavam recebendo infusão de propofol quando comparados com a infusão de midazolam. Concluímos que, em pacientes com choque séptico, a administração de midazolam resulta em uma melhora dos parâmetros microcirculatórios quando comparada com a administração de propofol. Essa diferença não pode ser atribuída a alterações de variáveis hemodinâmicas sistêmicas.

Submitted by Boris Flegr (boris@uerj.br) on 2021-01-05T18:07:46Z No. of bitstreams: 1 Leonardo de Souza Mendonca Tese completa.pdf: 2254035 bytes, checksum: 1bbcbeba1e946d3a47a9261135c5c349 (MD5) Made available in DSpace on 2021-01-05T18:07:46Z (GMT). No. of bitstreams: 1 Leonardo de Souza Mendonca Tese completa.pdf: 2254035 bytes, checksum: 1bbcbeba1e946d3a47a9261135c5c349 (MD5) Previous issue date: 2013-02-28 Fundação Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro The study aimed to investigate the effects of telmisartan (a partial PPAR gamma agonist), losartan (a pure angiotensin II receptor blocker) and rosiglitazone (PPAR gamma agonist) in a mice model of metabolic syndrome (MetS). The targets of this study were blood pressure (BP), carbohydrate metabolism, insulin resistance, inflammation, white adipose tissue (WAT) and liver. Male C57BL/6 mice were studied over 17 weeks after being separated into two major groups according to diet: standard chow (SC, 10% fat, n = 10) or high-fat high-salt chow (HFHS, 60% fat, 7% salt, n = 40). In the last 5 weeks of the experiment, the HFHS group was divided into four groups (n = 10): untreated HFHS, ROSI (HFHS plus rosiglitazone), TELM (HFHS plus telmisartan), and LOS (HFHS plus losartan). The HFHS group had significantly greater body mass and BP, in addition to hyperinsulinemia with insulin resistance, hyperleptinemia, adipocyte hypertrophy and hepatic steatosis as well as increased inflammatory cytokine levels. Animals treated with telmisartan had body weights similar to the SC group, in addition to reversed insulin resistance, reduced hypertension, reduced adipocyte hypertrophy, ameliorates hepatic steatosis and decreased IL-6. Telmisartan increased PPARγ and adiponectin expression in white adipose tissue. Interestingly, the expression of UCP-1 in white adipose tissue was also increased by treatment with telmisartan. Losartan decreased BP but had smaller effects on metabolic parameters. The present model of diet-induced weight gain and hypertension in mice mimics human features of MetS. In this model, telmisartan enhances UCP-1 expression in WAT, prevented weight gain and ameliorates insulin sensitivity and hepatic steatosis in C57Bl/6 mice, probably due to PPAR gamma activation. Este trabalho teve como objetivo investigar os efeitos da telmisartana (agonista PPAR-gama parcial), losartana (puro bloqueador do receptor AT1 da angiotensina II) e rosiglitazona (agonista PPAR-gama) em modelo experimental de síndrome metabólica. Os alvos do estudo foram a pressão arterial, metabolismo de carboidratos, resistência insulínica, inflamação, tecido adiposo e fígado. Camundongos C57BL/6 (a partir de 3 meses de idade) foram alimentados com dieta padrão (SC, n = 10) ou dieta hiperlipídica rica em sal (HFHS, n = 40) por 12 semanas. Após esse tempo, os animais do grupo HFHS foram subdivididos em 4 grupos (n = 10): HFHS (sem tratamento), ROSI (HFHS tratado com rosiglitazona), TELM (HFHS tratado com telmisartana) e LOS (HFHS tratado com losartana) por 5 semanas. O grupo HFHS apresentou um significante ganho de peso e aumento da pressão arterial sistólica, hiperinsulinemia com resistência insulínica, hiperleptinemia, hipertrofia de adipócitos bem como um quadro de esteatose hepática e níveis aumentados da citocina inflamatória interleucina-6 (IL-6). Os animais tratados com telmisartana chegou ao final do experimento com massa corporal similar ao grupo SC, com reversão do quadro de resistência insulínica, com pressão arterial normal, adipócitos de tamanho normal e sem apresentar esteatose hepática. Além disso, o tratamento com telmisartana aumentou a expressão de PPARγ e adiponectina no tecido adiposo epididimal. A expressão da proteína desacopladora-1 (UCP-1) no tecido adiposo branco (TAB) também foi aumentada. O tratamento com losartana diminuiu a pressão arterial para valores normais, porém com menores efeitos nos parâmetros metabólicos dos animais. O presente modelo experimental de ganho de peso e hipertensão induzidos por dieta mimetiza a síndrome metabólica humana. Neste modelo, a telmisartana aumentou a expressão de UCP-1 no TAB, preveniu o ganho de peso e melhorou a sensibilidade à insulina e a esteatose hepática dos camundongos C57BL/6, provavelmente devido à ativação PPAR-gama.

Submitted by Boris Flegr (boris@uerj.br) on 2021-01-06T20:53:06Z No. of bitstreams: 1 Sergio Emanuel Kaiser.pdf: 1530841 bytes, checksum: 92e8b80b17726b318ac5e8dbff0fcc88 (MD5) Made available in DSpace on 2021-01-06T20:53:06Z (GMT). No. of bitstreams: 1 Sergio Emanuel Kaiser.pdf: 1530841 bytes, checksum: 92e8b80b17726b318ac5e8dbff0fcc88 (MD5) Previous issue date: 2012-04-17 Capillary rarefaction and microcirculatory endothelial dysfunction are hallmarks of hypertension, rendering patients vulnerable to target organ lesions. The study aimed at assessing the effect of a six-month treatment period upon capillary density and microvascular reactivity to physiological and pharmacological stimuli. In addition, two different treatment strategies were tested for possible differences between effects upon those variables. A total of 44 patients were recruited, mean age 46.7±1.3 years and 20 normotensive individuals served as controls, mean age 48.0±1.6 years. Anthropometrical and laboratory data were collected, as well as plasma levels of vascular endothelial growth factor (VEGF), its receptor Flt-1 and nitric oxide (NO). Capillary density was obtained by intra-vital microscopy of the dorsum of the middle phalanx before and after post-occlusive reactive hyperemia (PORH). Capillary loops were counted by a semi-automated software. Microvascular reactivity was tested by laser Doppler flowmetry (LDF), and the challenges consisted of acetylcholine iontophoresis, local thermal hyperemia (LTH) and PORH. Patients were randomly allocated to either one of two treatment arms: metoprolol succinate uptitrated to 100 mg daily or olmesartan medoxomil uptitrated to 40 mg daily, with addition of hydrochlorothiazide if necessary. Controls underwent the same initial protocol and all tests were repeated in patients after six months. Baseline clinical and laboratory parameters were similar between patients and controls and between the two treatment groups. After six months there were slight, although significant, differences between the two groups in waist/hip ratio and HDL-cholesterol. In the whole cohort, pretreatment capillary density was significantly reduced compared to controls (71.3±1.5 vs 80.6±1.8 cap/mm2 p

Submitted by Boris Flegr (boris@uerj.br) on 2021-01-05T19:36:31Z No. of bitstreams: 1 TESE_FINAL_PUBLICADA_Flavio_Eduardo_Nacul.pdf: 750862 bytes, checksum: 2f5e04ef2167b0ecfb0d14a3a010e20b (MD5) Made available in DSpace on 2021-01-05T19:36:31Z (GMT). No. of bitstreams: 1 TESE_FINAL_PUBLICADA_Flavio_Eduardo_Nacul.pdf: 750862 bytes, checksum: 2f5e04ef2167b0ecfb0d14a3a010e20b (MD5) Previous issue date: 2012-03-29 Background: The use of vasoactive drugs to restore arterial blood pressure in patients with septic shock remains a cornerstone of intensive care medicine. However, vasopressors can accentuate the hypoperfusion of the gut during septic shock, allowing bacterial translocation and endotoxemia. In this study, we compared the effects of different vasoactive drugs on intestinal microcirculation and tissue oxygenation, independent of the effects of fluid therapy, in a rat model of endotoxemic shock. Methods: Pentobarbital-anesthetized Wistar Kyoto rats were submitted to endotoxemic shock induced by Escherichia coli lipopolysaccharide (2 mg/kg IV). Arterial blood pressure was normalized by a continuous infusion of different vasoactive drugs, including epinephrine, norepinephrine, phenylephrine, dopamine, dobutamine, or a combination of dobutamine and norepinephrine. The functional capillary density (FCD) of the muscular layer of the small intestine was evaluated by intravital video-microscopy. Mesenteric venous blood gases and lactate concentrations were also analyzed. Results: FCD decreased by approximately 25% to 60% after the IV infusion of epinephrine, norepinephrine, and phenylephrine. Administration of dopamine, dobutamine, and the combination of dobutamine and norepinephrine did not induce significant alterations in gut FCD. In addition, the mesenteric venous lactate concentration increased in the presence of phenylephrine and showed a tendency to increase after the administration of epinephrine and norepinephrine, whereas there was no observable increase after the administration of dopamine, dobutamine, and the combination of dobutamine with norepinephrine. Conclusion: This study confirms dissociation of the systemic hemodynamic and microvascular alterations in an experimental model of septic shock. Moreover, the results indicate that the use of dopamine, dobutamine, and dobutamine in combination with norepinephrine yields a protective effect on the microcirculation of the intestinal muscular layer in endotoxemic rats. Introdução: o uso de drogas vasoativas para restaurar a pressão arterial em pacientes com choque séptico é frequentemente utilizada em medicina intensiva. No entanto, os agentes vasopressores podem acentuar a hipoperfusão esplâncnica durante o choque séptico facilitando a translocação bacteriana e endotoxemia. Neste estudo foram comparados os efeitos de diferentes drogas vasoativas na microcirculação intestinal e nos parâmetros de oxigenação tecidual independentemente de reposição volêmica, num modelo experimental de choque séptico. Métodos: Ratos Wistar Kyoto anestesiados com pentobarbital foram submetidos a choque endotoxêmico através da administração de 2mg/Kg IV de lipopolissacarídeo da Escherichia Coli. A pressão arterial média foi restaurada através da administração de diversas drogas vasoativa, incluindo adrenalina, noradrenalina, fenilefrina, dopamina, dobutamina e uma combinação de noradrenalina com dobutamina. A densidade capilar funcional (DCF) da camada muscular do intestino delgado foi avaliada através de microscopia intravital. Gasometria e concentração de lactato da veia mesentérica superior também foram analisadas. Resultados: A DCF diminui aproximadamente 25% a 60% após a administração intravenosa de adrenalina, noradrenalina e fenilefrina. A administração de dopamina, dobutamina e da associação de noradrenalina com dobutamina não reduziu significativamente a DCF intestinal. A concentração de lactato da veia mesentérica aumentou após a administração de fenilefrina e mostrou uma tendência de aumentar após o uso de adrenalina e noradrenalina enquanto não se observou aumento de lactato após o uso de dopamina, dobutamina e da associação entre noradrenalina e dobutamina. Conclusões: O estudo confirma a presença de uma dissociação entre alterações hemodinâmicas sistêmicas e alterações microcirculatórias num modelo experimental de choque séptico. Os resultados indicam que o uso de dopamina, dobutamina e da associação entre noradrenalina e dobutamina apresentam um efeito de proteção na microcirculação da camada muscular intestinal de ratos submetidos a choque endotoxêmico.

Submitted by Boris Flegr (boris@uerj.br) on 2021-01-05T18:07:36Z No. of bitstreams: 1 Daniel Arthur Barata Kasal Tese Completa.pdf: 8208147 bytes, checksum: 6b47779d5f20a445260f2fcfd9b7b78c (MD5) Made available in DSpace on 2021-01-05T18:07:36Z (GMT). No. of bitstreams: 1 Daniel Arthur Barata Kasal Tese Completa.pdf: 8208147 bytes, checksum: 6b47779d5f20a445260f2fcfd9b7b78c (MD5) Previous issue date: 2011-02-16 Angiotensin (Ang) II and aldosterone (aldo) induce hypertension through mechanisms in part mediated by adaptive immunity and T responder lymphocytes. T regulatory (Treg) lymphocytes suppress pro-inflammatory mediators of the immune system. We questioned whether Treg adoptive transfer will blunt Ang II or aldo-induced hypertension and vascular injury, by evaluating two distinct protocols. In the Ang II protocol, male C57BL/6 mice were injected i.v. with Treg or T responder cells, and then infused with Ang II (1μg/kg/min) or saline, for 14 days. In the aldosterone protocol, another set of animals was injected with Treg or T responder cells, and then infused with aldosterone (600μg/kg/d) or saline, for the same period. The aldosterone group received saline 1% in drinking water. Both Ang II and aldosterone treated mice presented an increase in systolic blood pressure (43% and 31% respectively), of NADPH oxidase activity in aorta (1.5 and 1.9 fold, respectively) and heart (1.8 and 2.4 fold respectively) and an impaired vasodilatory response do acetylcholine (by 70% and 56% respectively), when compared to their controls (P

Submitted by Boris Flegr (boris@uerj.br) on 2021-01-06T20:52:46Z No. of bitstreams: 1 Vlander Gomes .pdf: 2536539 bytes, checksum: 4ec53a86d010583234e7f8c72ffb770d (MD5) Made available in DSpace on 2021-01-06T20:52:46Z (GMT). No. of bitstreams: 1 Vlander Gomes .pdf: 2536539 bytes, checksum: 4ec53a86d010583234e7f8c72ffb770d (MD5) Previous issue date: 2010-07-29 Myocardial Revascularization with cardiopulmonary bypass is associated with important modifications in the microcirculation and in the production and circulation of cytokines and inflammatory markers. In the present study 23 patients were evaluated on the day of the myocardial revascularization (baseline) and 7 and 28 days after the surgical procedure. The skin microcirculation that is in close relationship with coronary microcirculation was evaluated by iontophoresis of vasoactive substances, thermal hyperemia and post occlusive reactive hyperemia. The arterial stiffness was studied by digital pulse wave analysis. Cytokines and inflammatory markers such as C-reactive protein, nitrite/ nitrate, IL-6, Il-7, IL-8, IL-10, IFN-γ, TNF-α e G-CSF were also analyzed. A reduction in the skin microvascular vasodilatation was observed after iontophoresis of cumulative doses of acetylcholine (endothelium dependent) 7 and 28 days after the surgical procedure. Skin vasodilation after thermal hyperemia was more important before the surgery than 7 and 28 days after the procedure. The post occlusive reactive hyperemia did not cause vasodilation after 7 days of the surgery. After 28 days, the cutaneous microvascular conductance was higher than before. The iontophoresis of sodium nitroprusside (endothelium independent) showed increasing vasodilation according to the doses/ charge applied but there was no difference among the days of the study. The level of IL-6 and IL-8 increased after 7 days and the level of IL-8 returned to baseline after 28 days. IL-6 showed a reduction after 28 days but did not reach the baseline. IFN-γ, TNF-α e G-CSF were detected only on the day of the surgical procedure and the level of IL-7 and IL-10 was similar before, 7 days and 28 days after the surgery. Nitrite/ nitrate was reduced after 7 days of the surgical procedure. In conclusion we observed that the small difference between endothelium dependent vasodilation 7 days after the surgical procedure showed a reduction in the alterations caused by the extracorporeal circulation and the constant level of vasodilation after 28 days showed the complete recovery of the endothelium. This result was in accordance with thermal hyperemia and post occlusive reactive hyperemia. The kinetics ofIL-6, IL-8 C-reactive protein were similar. The arterial stiffness did not show any difference. A Cirurgia de Revascularização do Miocárdio, realizada com o auxílio da Circulação Extracorpórea, está associada a alterações importantes na microcirculação e na produção e circulação de citocinas e marcadores inflamatórios. No presente estudo, foram avaliados 23 pacientes com indicação de Revascularização do Miocárdio, no dia do procedimento e 7 e 28 dias após a cirurgia. A microcirculação cutânea, enquanto reflexo da microcirculação coronariana, foi estudada através da hiperemia térmica e/ ou reativa pós oclusiva e da iontoforese de substâncias vasoativas por mecanismos dependentes e independentes do endotélio. A rigidez arterial foi aferida através da análise da onda de pulso digital. Foi avaliado ainda o impacto da doença e do procedimento cirúrgico sobre a produção e circulação sérica de citocinas e marcadores inflamatórios, tais como: PCR-HS, nitrito/ nitrato, IL-6, Il-7, IL-8, IL-10, IFN-γ, TNF-α e G-CSF. Foi observada uma tendência à redução da vasodilatação da microcirculação cutânea após a administração de doses acumulativas de acetilcolina (endotélio dependente) através da iontoforese de 7 e 28 dias após o procedimento cirúrgico. A hiperemia térmica foi mais pronunciada na avaliação basal do que aos 7 e 28 dias. A hiperemia reativa pós oclusiva não demonstrou alterações 7 dias após o procedimento. Aos 28 dias, houve um aumento da condutância microvascular cutânea. Quando avaliada a vasodilatação endotélio-independente (nitroprussiato de sódio), observamos aumento do fluxo microvascular cutâneo diretamente proporcional à carga/ dose aplicada, sem diferenças nos valores obtidos no basal e 7 e 28 dias após o procedimento. A rigidez arterial não apresentou alterações. A análise dos fatores inflamatórios e das citocinas demonstrou aumento marcante da IL-6 e da IL-8 após 7 dias do procedimento cirúrgico, com retorno parcial aos níveis basais da IL-6 e total da IL-8 após 28 dias. O IFN-γ, TNF-α e G-CSF apenas apresentaram níveis detectáveis na avaliação basal e IL-7 e IL-10 não demonstraram alterações significativas nos tempos avaliados. A PCR-HS demonstrou níveis mais elevados após 7 dias e retorno parcial aos níveis basais após 28 dias. O nitrito/ nitrato, após 7 dias, apresentou leve queda em sua concentração plasmática. Concluímos que a pequena diferença entre o valores obtidos entre o basal e após 7 dias do procedimento cirúrgico com a iontoforese de acetilcolina resulta em minimização do impacto endotelial e um valor constante deste dado após 28 dias, sugere recomposição fisiológica completa. Este resultado foi semelhante com a análise da hiperemia térmica e reativa pós oclusiva. As interleucinas IL-6 e IL-8, bem como a PCR-HS apresentaram comportamento correlacionável, refletindo a cinética inflamatória. A rigidez arterial não demonstrou alterações.

Submitted by Boris Flegr (boris@uerj.br) on 2021-01-05T18:07:41Z No. of bitstreams: 1 Tese oficial completa.pdf: 9122139 bytes, checksum: c42f1e82e70f83bc665a2d196ee7de81 (MD5) Made available in DSpace on 2021-01-05T18:07:41Z (GMT). No. of bitstreams: 1 Tese oficial completa.pdf: 9122139 bytes, checksum: c42f1e82e70f83bc665a2d196ee7de81 (MD5) Previous issue date: 2010-07-21 Maternal high-fat diet (HF) during gestation and/or lactation period increases the susceptibility to development of chronic disease in offspring adult life. This work aimed to verify the hypothesis that maternal intake of high-fat diet in critical periods of pregnancy and/or suckling period predisposes to non alcoholic fatty liver disease, pancreatic and adipose tissue alterations in adulthood mice offspring. C57BL/6 female mice were fed, during gestation and/or lactation phases, with standard chow (SC) or HF diet. Male pups were divided into 5 groups: SC- from SC fed dam; G- from HF fed dam during gestation period; L- from HF fed dam during lactation period; GL- from HF fed dam during gestation and lactation periods and GL/HF- from HF fed dam during gestation and lactation, maintaining HF diet from post-weaning to adulthood. We analyzed body mass in all experiment, and at the euthanasia (3 mo-old), liver, pancreas and adipose tissue were removed, weighted and embedded. Blood was collected to biochemical analyses. At birth and at weaning, GL/HF pups were heavier than SC pups (+6% and +44%, p

Submitted by Boris Flegr (boris@uerj.br) on 2021-01-06T20:57:14Z No. of bitstreams: 1 Dissertacao-Alessandra S M F da Costa.pdf: 1148687 bytes, checksum: 2d0afb09d4d2095bf76217bd81f403b1 (MD5) Made available in DSpace on 2021-01-06T20:57:14Z (GMT). No. of bitstreams: 1 Dissertacao-Alessandra S M F da Costa.pdf: 1148687 bytes, checksum: 2d0afb09d4d2095bf76217bd81f403b1 (MD5) Previous issue date: 2010-03-03 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Endothelial dysfunction in patients with type 1 diabetes appears to be an early event in the genesis of vascular complications. The purpose of the present study is to assess endothelial function in the microcirculation and arterial stiffness, by comparing with non-diabetic controls, and correlating with clinical, demographic and laboratorial parameters. We evaluated 57 patients with type 1 diabetes aged 32.5 (13-61) years and with a disease duration of 15 (1-48)years, and 53 controls using laser Doppler flowmetry during low-current iontophoresis of acetylcholine (ACh) (endothelium dependent response), post occlusive reactive hyperemia(PORH) and maximum vasodilator function during thermal hyperemia. Endothelium-independent response was measured after iontophoresis of sodium nitroprusside (SNP).The peripheral pressure waveform was analyzed to assess the arterial stiffness. Diabetic patients underwent clinical and laboratory evaluation (smoking, disease duration, daily insulin dose, use of medications that could improve endothelial function such as antihypertensive drugs and statins, blood pressure, body mass index, urinary albumin excretion, lipid profile, glycemic control and C-reactive protein levels-CRP). Mean resting microvascular flux did not differ between control subjects and patients with type 1 diabetes, as well as arterial stiffness assessed through stiffness index and reflection index. Microvascular response to ACh was significantly reduced in patients (p=0,002). However, despite the reduction ofAUC NPS, the analysis with repeated measures disclosed no difference between the groups in relation to the doses (p=0,15). Maximal skin microvascular vasodilation induced by thermal hyperemia was found to be higher in the control group than among patients (93,6(24,5-379-,9) e 56,6(31,5-204,5), respectively p=0,04). On the other hand, during PORH, maximal increase in flux and area under the curve of the hyperemic response did not differ between patients and controls, although the time frame to reach maximum flux and the time to half recovery after hyperemia was longer in patients than in controls (P=0.02) . Uric acid, hba1c, age and CRP were the most important contributing factors to the variation of microvascular reactivity, while disease duration, the diastolic arterial pressure and HDL cholesterol were independently associated to arterial stiffness. Despite the correlation between drugs with hemorheologycal properties and arterial stiffness, the exclusion of patients who were taking such substances did not affect the results. We conclude that in the studied population of type 1 diabetic patients, the endothelium-dependent vascular responses and maximal vasodilator capacity are significantly reduced. In what concerns arterial stiffness, our study disclosed no difference between diabetics and controls. Moreover, Acetylcholine response can be correlated to arterial stiffness in diabetics, and further studies aiming at the evaluation of the micro and macrovascular reactivity should be performed with consumers of drugs which may be likely to affect the endothelial function. A disfunção endotelial tem sido sugerida como evento precoce na patogênese das complicações vasculares do DM1. O presente estudo objetivou avaliar a função endotelial na microcirculação e rigidez arterial no diabetes tipo 1 comparando com controles não diabéticos e correlacionando com variáveis clínicas, demográficas e laboratoriais. Foram avaliados 57 pacientes com diabetes tipo 1 com idade de 32,5 (13-61) anos e duração de doença de 15 (1-48) anos e 53 controles através de fluxometria cutânea por laser-Doppler após iontoforese de Acetilcolina(ACh) (resposta endotélio dependente), hiperemia reativa pós oclusiva(HRPO) e a capacidade máxima de vasodilatação após hiperemia térmica. Já a resposta endotélio independente foi avaliada após iontoforese de Nitroprussiato de sódio (NPS). A rigidez arterial foi mensurada através da análise da onda de pulso digital com os índices de rigidez arterial e de reflexão. Os pacientes diabéticos foram submetidos à avaliação clínica e laboratorial (histórico de tabagismo, dose diária de insulina, duração do diabetes, uso de drogas que alteram a função endotelial como anti-hipertensivos e estatinas, níveis pressóricos, índice de massa corporal, excreção urinária de albumina, perfil lipídico, controle glicêmico e níveis de proteína C-reativa). O fluxo microvascular médio em repouso não foi diferente entre pacientes e controles , assim como a complacência arterial mensurada através do índice de rigidez arterial e do índice de reflexão. A resposta vascular a vasodilatação mediada pela ACh encontrou-se significantemente reduzida nos pacientes (p=0,002). No entanto, apesar da diferença verificada na área abaixo da curva de NPS em relação ao controle, a análise por medidas repetidas não apontou diferença entre os grupos em relação às doses entre os grupos (p=0,15). A vasodilatação cutânea máxima induzida pela hiperemia térmica foi maior entre os controles em comparação com os diabéticos 93,6(24,5-379-,9) e 56,6(31,5-204,5), respectivamente p=0,04. Por outro lado, durante a HRPO, o aumento máximo no fluxo e a área abaixo da resposta hiperêmica não divergiram entre pacientes e controles, embora o tempo para alcançar o fluxo máximo tenha sido maior nos diabéticos do que nos controles(p=0,02). As principais variáveis correlacionadas com a microcirculação foram o ácido úrico, a hemoglobina glicada, a idade e a proteína C reativa, e com a rigidez arterial, foram a duração do Diabetes, a Pressão arterial diastólica e o HDL. Apesar da correlação entre o uso de drogas com propriedades hemorreológicas e a rigidez arterial, a exclusão dos pacientes usuários daqueles medicamentos não alterou os resultados obtidos. Concluímos que, na população de diabéticos tipo 1 estudada, a resposta vascular endotélio dependente, e a capacidade máxima de vasodilatação estão significativamente reduzidas. Não houve diferença entre diabéticos e controles quanto à rigidez arterial. Ademais, a vasodilatação microcirculatória mediada pela Acetilcolina pode ser correlacionada com a rigidez arterial em diabéticos. Estudos posteriores devem ser realizados no intuito de avaliar a influência exercida pelas drogas que alteram a função endotelial sobre a reatividade micro e macrovascular.

Submitted by Boris Flegr (boris@uerj.br) on 2021-01-06T20:54:32Z No. of bitstreams: 1 Tese final1.pdf: 1240852 bytes, checksum: e4bcb6efa28717cc0968db2dde911d08 (MD5) Made available in DSpace on 2021-01-06T20:54:32Z (GMT). No. of bitstreams: 1 Tese final1.pdf: 1240852 bytes, checksum: e4bcb6efa28717cc0968db2dde911d08 (MD5) Previous issue date: 2010-02-03 Recent clinical evidence suggests that calcium-rich diets help reduce body weight and abdominal obesity; increase insulin sensitivity; enhance lipid profile; modulate blood pressure and reduces the inflammatory state associated with obesity. The Objective: evaluate the effects of dietary calcium during energy restriction on weight loss, body fat, abdominal obesity, glucose metabolism, lipid profile, leptin levels, blood pressure, biomarkers of inflammation, fibrinolysis, biomarkers of endothelial function and calcium metabolism in obese subjects. The study was a randomized clinical trial. The participants were randomized into a low calcium diet (LCD) (

Submitted by Boris Flegr (boris@uerj.br) on 2021-01-06T20:58:37Z No. of bitstreams: 1 Alessandro Rodrigues do Nascimento Final.pdf: 855907 bytes, checksum: 090cf11a9286a3b7fda734d0aa96817c (MD5) Made available in DSpace on 2021-01-06T20:58:37Z (GMT). No. of bitstreams: 1 Alessandro Rodrigues do Nascimento Final.pdf: 855907 bytes, checksum: 090cf11a9286a3b7fda734d0aa96817c (MD5) Previous issue date: 2009-08-24 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Essential hypertension (EH) is characterized by chronic increases in peripheral vascular resistance, mainly resulting from functional and structural alterations of the microcirculation. Moreover, a reduction of arteriolar and capillary density (microvascular rarefaction) is involved in the increase of arterial pressure in EH. In addition, central sympathetic overactivity is involved in the pathophysiology of functional and structural alterations of the cardiovascular system in EH. In the present work, we investigated the effects of a long-term treatment (28 days) with centrally-acting antihypertensive drugs on functional and/or structural capillary rarefaction in the skin, skeletal muscle and heart of adult spontaneously hypertensive rats (SHR), a classical experimental model of EH. We also investigated the effects of the treatments on left ventricular mass in SHR. Wistar Kyoto rats were used as normotensive controls. We used equipotent anihypertensive doses of clonidine (0.1 mg/kg/day), rilmenidine (1 mg/kg/day) and moxonidine (10 mg/kg/day). Functional capillary density was evaluated using epi-illuminated fluorescence video-microscopy while structural capillary density was studied using a histochemical tracer of capillaries. Our results showed that there was an increase in the number of spontaneously perfused capillaries (functional density) in the skin and skeletal muscle of SHR in all treatment groups, when compared to the non-treated SHR group. Moreover, there was a reversion of structural capillary rarefaction in the skeletal muscle with all drug treatments. On the other hand, there was no reversion of structural capillary rarefaction of the left ventricle in any experimental group. Finally, left ventricular hypertrophy was partially reversed in the group of SHR treated with rilmenidine. In conclusion, our results showed that besides arterial pressure reduction, long-term treatment with centrally-acting antihypertensive drugs induces a reversal of microcirculatory alterations in SHR and rilmenidine favors the regression of left ventricular hypertrophy. The results also suggest that the modulation of central sympathetic overactivity induces beneficial effects on the microcirculation in the hypertensive disease. A hipertensão arterial sistêmica (HAS) caracteriza-se pelo aumento crônico da resistência vascular periférica, determinado essencialmente na microcirculação, que resulta de alterações vasculares funcionais e estruturais. Além disso, a redução da densidade arteriolar e capilar (rarefação da microcirculação) contribui para a elevação da pressão arterial na HAS. Nesse contexto, sabe-se que a hiperatividade do sistema nervoso simpático central está envolvida na fisiopatologia das alterações tanto funcionais quanto estruturais da HAS. No presente trabalho, investigamos os efeitos do tratamento crônico (28 dias) com anti-hipertensivos de ação central sobre a rarefação capilar funcional e/ou estrutural na pele, músculo esquelético e miocárdio de ratos espontaneamente hipertensos (SHR) adultos, modelo clássico de hipertensão arterial primária. Os ratos Wistar Kyoto (WKY) foram utilizados como controles normotensos. Foram utilizadas doses equipotentes de clonidina (0,1 mg/kg/dia), rilmenidina (1 mg/kg/dia) e moxonidina (10 mg/kg/dia), com relação ao efeito anti-hipertensivo. Também foram estudados os efeitos dos tratamentos sobre a massa ventricular esquerda. Para avaliação da densidade capilar funcional utilizamos microscopia por epi-iluminação e fluorescência e para avaliação da densidade capilar estrutural técnicas de marcação histoquímica dos capilares. Os resultados mostraram que houve aumento do número de capilares espontaneamente perfundidos (densidade funcional) na pele e no músculo esquelético de SHR tratados com todos os fármacos, com relação ao grupo SHR não tratado. Além disso, foi observada reversão da rarefação capilar estrutural no músculo esquelético de SHR com todas as drogas utilizadas. Por outro lado, não houve reversão da rarefação capilar estrutural no ventrículo esquerdo em nenhum grupo experimental. Finalmente, a hipertrofia do ventrículo esquerdo foi parcialmente revertida em SHR tratados com rilmenidina. Em conclusão, nossos resultados demonstraram que, além da redução da pressão arterial, a utilização de agentes anti-hipertensivos de ação central resulta na reversão de alterações microcirculatórias de ratos espontaneamente hipertensos e o uso de rilmenidina favorece a regressão da hipertrofia cardíaca. Os resultados também sugerem que a inibição da hiperatividade simpática central induz efeitos benéficos na microcirculação na hipertensão arterial.