Influência do ácido orótico no metabolismo energético cardíaco de ratos

Abstract

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 forcardiac 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, andcorroborated 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 aftercoronary 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-Pglycolytic 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 preischemiayet. 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 contractilefunction.