Efeitos do bloqueio precose da aldosterona na estrutura e função cardíaca e na composição da matriz colágena miocárdica de ratos espontaneamente hipertensos
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Data
2013-02-27
Autores
Cezar, Marcelo Diarcadia Mariano [UNESP]
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Universidade Estadual Paulista (Unesp)
Resumo
A hipertensão arterial sistêmica é uma das principais causas de insuficiência cardíaca (IC). Durante o desenvolvimento de hipertrofia miocárdica e a evolução para IC, ocorre ativação dos sistemas nervoso simpático e reninaangiotensina- aldosterona. Estudos clínicos e experimentais mostraram que a aldosterona exerce diversos efeitos deletérios sobre o sistema cardiovascular e que o bloqueio de sua ação melhora a sobrevida e atenua o remodelamento ventricular na IC avançada. Entretanto, poucos estudos avaliaram as consequências de seu bloqueio na hipertensão arterial, antes do surgimento de sinais de IC. Assim, o objetivo deste estudo foi avaliar o efeito da administração precoce de espironolactona sobre variáveis estruturais e funcionais cardíacas de ratos espontaneamente hipertensos (SHR) e, adicionalmente, investigar os componentes responsáveis pela remodelação da matriz extracelular. Ratos SHR com 13 meses de idade foram divididos em dois grupos: um grupo SHR controle (SHR-C, n=20) e outro grupo SHR tratado com espironolactona (20 mg/kg/dia) (SHR-ESP, n=24) por seis meses. Ratos Wistar-Kyoto (WKY-C, n=15) de mesma idade foram utilizados como controle. A pressão arterial sistólica (PAS) foi medida no início e no final do experimento. A avaliação estrutural e funcional in vivo do coração foi realizada por meio de ecocardiograma. A função miocárdica in vitro foi avaliada em preparações de músculo papilar isolado do ventrículo esquerdo (VE). As análises séricas de eletrólitos e creatinina foram realizadas por kits bioquímicos específicos. Para análise de variáveis anatômicas foram medidos os pesos úmidos e secos do VE, ventrículo direito (VD), átrios e amostras de fígado e pulmão. Amostras de tecido do VE foram obtidas para análises histológicas, quantificação de hidroxiprolina e das concentrações de colágeno total e solúvel, e avaliação das express de Bonferroni para as variáveis peso...
Hypertension is a leading cause of heart failure (HF). During the development of myocardial hypertrophy and progression to heart failure there is activation of sympathetic nervous and renin-angiotensin-aldosterone systems. Clinical and experimental studies have shown that aldosterone exerts several deleterious effects on cardiovascular system and that blocking its action improves survival and attenuates ventricular remodeling in advanced HF. However, few studies have evaluated the consequences of aldosterone blockade in hypertensive cardiopathy before clinical evidence of HF. The purpose of this study was to evaluate the effects of early spironolactone (SPR) administration on cardiac structure and function in spontaneously hypertensive rats (SHR) and to investigate extracellular matrix remodeling. Forty-four 13 month old SHR were divided into two groups: control SHR (SHR-C, n=20) and SHR treated with SPR 20 mg/kg/day (SHR-SPR, n=24) for six months. Age-matched Wistar- Kyoto rats (WKY-C, n=15) were used as controls. Systolic blood pressure (SBP) was measured at the beginning and end of the experiment. Echocardiogram was performed to evaluate in vivo cardiac structures and left ventricular (LV) function. Myocardial function was analyzed in LV papillary muscle preparations. Serum electrolytes and creatinine levels were determined by specific biochemical kits. Wet and dry weights of LV, right ventricle, atria, and liver and lung samples were measured. LV tissue samples were obtained for histological analysis, determination of hydroxyproline and total and soluble collagen concentration, and evaluation of types I and III collagen, and lysyl oxidase gene and protein expressions. Statistical analysis was performed by one-way ANOVA and Bonferroni’s test or one-way Kruskal-Wallis and Dunn’s test (WKY-C vs. SHR-C and SHR-C vs. SHR-SPR), and two-way repeated measures ANOVA with Bonferroni’s test for body ...
Hypertension is a leading cause of heart failure (HF). During the development of myocardial hypertrophy and progression to heart failure there is activation of sympathetic nervous and renin-angiotensin-aldosterone systems. Clinical and experimental studies have shown that aldosterone exerts several deleterious effects on cardiovascular system and that blocking its action improves survival and attenuates ventricular remodeling in advanced HF. However, few studies have evaluated the consequences of aldosterone blockade in hypertensive cardiopathy before clinical evidence of HF. The purpose of this study was to evaluate the effects of early spironolactone (SPR) administration on cardiac structure and function in spontaneously hypertensive rats (SHR) and to investigate extracellular matrix remodeling. Forty-four 13 month old SHR were divided into two groups: control SHR (SHR-C, n=20) and SHR treated with SPR 20 mg/kg/day (SHR-SPR, n=24) for six months. Age-matched Wistar- Kyoto rats (WKY-C, n=15) were used as controls. Systolic blood pressure (SBP) was measured at the beginning and end of the experiment. Echocardiogram was performed to evaluate in vivo cardiac structures and left ventricular (LV) function. Myocardial function was analyzed in LV papillary muscle preparations. Serum electrolytes and creatinine levels were determined by specific biochemical kits. Wet and dry weights of LV, right ventricle, atria, and liver and lung samples were measured. LV tissue samples were obtained for histological analysis, determination of hydroxyproline and total and soluble collagen concentration, and evaluation of types I and III collagen, and lysyl oxidase gene and protein expressions. Statistical analysis was performed by one-way ANOVA and Bonferroni’s test or one-way Kruskal-Wallis and Dunn’s test (WKY-C vs. SHR-C and SHR-C vs. SHR-SPR), and two-way repeated measures ANOVA with Bonferroni’s test for body ...
Descrição
Palavras-chave
Insuficiencia cardiaca, Hipertensão - Tratamento, Colageno, Diureticos - Uso terapêutico, Hormonios esteroidianos, Hypertension
Como citar
CEZAR, Marcelo Diarcadia Mariano. Efeitos do bloqueio precose da aldosterona na estrutura e função cardíaca e na composição da matriz colágena miocárdica de ratos espontaneamente hipertensos. 2013. 64 f. Tese (doutorado) - Universidade Estadual Paulista Julio de Mesquita Filho, Faculdade de Medicina de Botucatu, 2013.