Influência do ácido orótico no metabolismo energético cardíaco de ratos

• Main Author: Laura Cristina Jardim Porto
• Other Authors: Leida Maria Botion
• Format: Others
• Language: Portuguese
• Published: Universidade Federal de Minas Gerais 2007
• Online Access: http://hdl.handle.net/1843/MCSC-7C6S45

=== The functional cardiac performance is closely related to energetic metabolism. Studies have shown that the disarrangements usually associated to ischemia and reperfusion, such as ionic imbalance and impairment of contratiles proteins, are consequence of installed metabolic changes, associated with a reduction of ATP levels. Several experimental and clinical researches have shown that therapeutic agents that optimize the energetic metabolism constitute important approach for cardiac disorders treatment. Considering that the orotic acid (OA) exhibit beneficials cardiovascular effects, the experiments reported here were designed to investigate the influence of this compound on the metabolic pathway involved in energy supply to heart. Male Wistar rats were fed during nine days with a balanced diet (C control group) or with a C diet supplemented with 1% OA (OA group). The treatment with OA increased the cardiac utilization of fatty acids (FA), evidenced by the cardiac increase of uptake and incorporation of FA, and corroborated by increased activity of LPL, and genetic expression of peroxisome proliferator activated receptor alpha, carnitine palmitoyl transferase and acyl CoA oxidase, both in basal conditions and after coronary partial occlusion. In relation to cardiac metabolism of glucose, OA administration increased the glucose uptake, the cardiac glycogen content, the concentration of the glucose 6-P and frutose 6-P glycolytic intermediates and the lactate production, in basal conditions and after coronary partial occlusion. These effects in the OA group resulted in an increased fuel supply to the heart in preischemia yet. It was evidenced, on AO animals, a stimulus of glycolytic pathway and FA oxidation, particularly important to residual ATP pool handling during the ischemic phase. The analysis of the cardiac contactility index showed a positive inotropic effect of OA due, at least in part, to the increased availability of energy. This allow us to suggest that the metabolic changes induced by OA administration results in appreciable alteration on myocardial contractile function. === A performance cardiaca funcional esta intimamente relacionada ao metabolismo energetico. Estudos mostram que os desarranjos comumente associados a isquemia e reperfusao, como desequilibrio ionico e comprometimento das proteinas contrateis, sao consequentes as mudancas metabolicas instaladas, sendo chave nessa questao a diminuicao do pool de ATP. Varias pesquisas experimentais e clinicas tem revelado que agentes terapeuticos que otimizam o metabolismo energetico cardiaco constituem importante enfoque para o tratamento das disfuncoes cardiacas. Considerando que o acido orotico (AO) apresenta efeitos cardiovasculares beneficos, o presente estudo objetivou investigar a influencia desse composto nas vias metabolicas envolvidas no suprimento de energia para o coracao. Ratos Wistar machos foram alimentados por nove dias com dieta controle (grupo C) ou com dieta C suplementada com AO a 1% (grupo AO). O tratamento com AO aumentou a utilizacao cardiaca de acidos graxos (AG), evidenciada pelos aumentos da captacao e incorporacao dos mesmos pelo tecido cardiaco e corroborado pelos aumentos da atividade da enzima LPL, da expressao dos genes para PPAR¿, carnitina palmitoil transferase-1 e acil CoA oxidase, tanto em condicoes basais quanto apos oclusao parcial da coronaria. No que se refere ao metabolismo cardiaco da glicose, a administracao AO aumentou a captacao da mesma, o conteudo de glicogenio, a concentracao dos intermediarios glicoliticos glicose 6-P e frutose 6-P e a producao de lactato, em ambas as condicoes experimentais, basal e apos oclusao parcial da coronaria. Isso se refletiu em aumento do conteudo energetico cardiaco ainda na pre-isquemia. Foi evidenciado, nos animais AO, um estimulo da via glicolitica e da oxidacao de AG, particularmente importante para manutencao do pool residual de ATP durante a fase isquemica. A analise dos indices de contratilidade cardiaca revelou um efeito inotropico positivo do AO, fato que se deve, pelo menos em parte, ao maior rendimento energetico alcancado. Isso nos permite sugerir que as modificacoes metabolicas induzidas pelo acido orotico repercutem em alteracoes apreciaveis na funcao contratil do miocardio.