Objetivos de este trabajo: 1) Explorar mediante un anticuerpo policlonal antiAE3 con acción inhibitoria, si esta isoforma es responsable de la mayor actividad AE observada en el MH. 2) Determinar si la hiperactividad AE causa hiperactividad compensatoria del NHE-1. 3) Verificar si la inhibición prolongada de la AE modifica la hipertrofia del MH.

Made available in DSpace on 2015-07-22T20:49:54Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-11-25. Added 1 bitstream(s) on 2015-08-11T03:26:00Z : No. of bitstreams: 1 Publico-12000.pdf: 924353 bytes, checksum: e021689525ddc32c47a2d833714071cb (MD5) / Background: Sustained β-adrenoreceptor activation promotes cardiac hypertrophy and cellular injury. Aims: To evaluate the cardioprotective effect of exercise on damage induced by β-adrenergic hyperactivity. Methods: Male Wistar rats were randomised into four groups (n = 8 per group): sedentary non-treated control (C), sedentary treated with isoproterenol 0.3 mg/kg/day administered subcutaneously for 8 days (I), exercised non-treated (E) and exercised plus isoproterenol administered during the last eight days of exercise (IE). Exercised animals ran on a treadmill for 1 h daily 6 times a week for 13 weeks. Results: Isoproterenol caused increases in left ventricle (LV) wet and dry weight/body weight ratio, LV water content and cardiomyocyte transverse diameter. Additionally, isoproterenol induced severe cellular lesions, necrosis, and apoptosis, increased collagen content and reduced capillary and fibre fractional areas. Notably, all of these abnormalities were completely prevented by exercise. Conclusion: Our data have demonstrated that complete cardioprotection is possible through exercise training; by preventing β-adrenergic hyperactivity-induced cardiac hypertrophy and structural injury. Abstracts do artigo 2: To test the hypothesis that exercise training can prevent the myocardial dysfunction and to inhibit the left ventricular (LV) remodeling induced by β-adrenergic hyperactivity, Wistar male rats were assigned to four groups: sedentary non-treated (CON), sedentary isoproterenol- treated (ISO), exercised non-treated (EX), and exercised plus isoproterenol (I+E). Echocardiography, hemodynamic and isolated papillary muscle were used for functional evaluations. Real time RT-PCR and western blot were used to quantify TNF-α, IL-6, IL-10 and TGF-β1 in the tissue. The nuclear NF-кB expression was evaluated by immunohistochemical staining. The ISO rats showed a concentric hypertrophy of LV. These animals exhibited marked increases in LV end-diastolic pressure and impaired myocardial performance in vitro by reducing the developed tension and maximum rate of tension increase and decrease, as well as worsened recruitment of the Frank-Starling mechanism. Both gene and protein levels of TNF-α and IL-6 as well as the TGF-β1 mRNA were also increased. In addition, the nuclear NF-kB expression in the ISO group was significantly raised. In the I+E group, the exercise training (i) prevented LV hypertrophy, (ii) improved myocardial contractility, (iii) avoided the increase of pro-inflammatory cytokines and improved IL-10 levels, and (iiii) attenuated the increase of TGF-β1 mRNA. Thus, exercise training in a model of β-adrenergic hyperactivity can avoid the adverse remodeling of LV and improve the myocardial contractile. It appears likely that the cardioprotection is related to beneficial effects of exercise on balance between pro- and anti-inflammatory cytokines, and mitigates the expressions of TGF-β1 / TEDE / BV UNIFESP: Teses e dissertações

Orientador: Silméia Garcia Zanati Bazan / Resumo: Fundamento: A história de pré-eclâmpsia (PE) tem sido associada a doença cardiovascular em mulheres. Existem evidências de que alterações cardiovasculares decorrentes da PE podem permanecer mesmo após o término da gestação.Objetivos: 1-avaliar a frequência de fatores de risco cardiovascular em mulheres com história de PE há 12 meses e sua associação com hipertrofia miocárdica e espessura médio-intimal de carótidas (EMIC); 2-avaliar o efeito da hipertrofia miocárdica na função do ventrículo esquerdo e na capacidade funcional.Métodos: Estudo prospectivo transversal incluindo 118 pacientes consecutivas com história de PE há 12 meses. Foram efetuadas avaliações clínicas e laboratoriais, ecocardiograma, teste ergométrico e ultrassom de carótidas. A hipertrofia miocárdica (HVE) foi definida para massa miocárdica indexada ≥ 45 g/m2,7. Foram consideradas como EMIC aumentadas quando as medidas estivessem acima do percentil 75 para a faixa etária. Foram considerados os fatores de risco clássicos para doença cardiovascular e calculado o escore de risco cardiovascular global em 30 anos (RCVG_30). Os dados foram analisados por meio de regressão logística ou linear e coeficiente de correlação de Spearman. Nível de significância p<0,05.Resultados: A hipertensão arterial sistêmica (HAS) foi identificada em 52 pacientes (44%), sobrepeso/obesidade (Sob/obes) em 82 (69%), dislipidemia em 68 (57%) e síndrome metabólica em 47 pacientes (40%). Um total de 48 mulheres (41%) apresentaram RCVG_... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Background: A history of preeclampsia (PE) has been associated with cardiovascular disease in women. There is substantial evidence that cardiovascular alterations resulting from PE can persist even after termination of pregnancy.Objectives: 1-evaluate the frequency of cardiovascular risk factors in women with 12-month history of PE and their association with myocardial hypertrophy and carotid intima-media thickness (CIMT); 2-evaluate the effect of myocardial hypertrophy on left ventricular function and functional capacity.Methods: Transversal prospective study including 118 consecutive patients with 12-month PE history. Clinical and laboratory evaluations, echocardiogram, ergometric and carotid ultrasound were performed. Myocardial hypertrophy (LVH) was defined as indexed myocardial mass ≥ 45 g/m2,7. CMIT was considered elevated when the measures were above the 75th percentile for the age range. The classical risk factors for cardiovascular disease were considered, and the 30-year global cardiovascular risk score was calculated (GCVR_30). The data were analyzed by linear or logistic regression and Spearman’s correlation coefficient. Significance level p<0.05.Results: Systemic arterial hypertension (SAH) was identified in 52 patients (44%), overweight/obesity (OOB) in 82 (69%), dyslipidemia in 68 (57%) and metabolic syndrome in 47 patients (40%). A total of 48 women (41%) presented GCVR _30 greater than or equal to 10%, with these patients aged 34±5.4 years. LVH was pres... (Complete abstract click electronic access below) / Doutor