Prevention of processes coupled with free radical formation prevents also the development of calcium-resistance in the diabetic heart

Recently it was shown that besides their negative role in pathogenesis of d iabetes, reactive oxygen species (ROS) and particularly the products of non -enzymatic glycation of proteins (NEGP) may also participate in some proces ses of adaptation of the myocardium to diabetes, such as in the mechanism o f development of calcium resistance of the heart. Our study revealed that t he hearts of rats with experimentally induced diabetes (single dose of stre ptozotocin, 45 mg/kg i.v., 6 U/kg insulin daily) develop considerable resis tance against calcium overload (induced by means of Ca-paradox). On the day 63 after the beginning of experiment, when the diabetic cardiomyopathy bec ame fully developed but the hearts were still not failing, their calcium re sistance was increased to 83.33 %. Our results provide evidence that, when applied in a special regimen, resorcylidene aminoguanidine (RAG, 4 mg/kg) p revented both, the formation of fructosamine (a source of ROS generation), and also that of the advanced Maillard products, in the heart sarcolemma of diabetic rats. The effect of RAG was accompanied by a decrease in calcium resistance in the group of rats with chronic diabetes (63 days) from 83.3 t o 46.7 %. It is concluded that NEGP and ROS formation are inevitably needed for development of calcium resistance in the diabetic hearts.