Analysis of Mechanisms Underlying the Development of Endothelial Dysfunction and Functional Disorders in Experimental...

On the model of alloxan-induced diabetes mellitus in rats, the development of oxidative stress and violation of the NO-producing function of the endothelium and internal organs was established. Structural changes in the vascular endothelium due to increased level of atherogenic LDL preventing access of L-arginine to endothelial NO synthase (eNOS) contribute to the development of endothelial dysfunction, which is paralleled by oxidative modification of L-arginine and the formation of inhibitors of eNOS expression (asymmetric dimethylarginine, L-NAME). These findings are indicative of reduced eNOS expression in experimental diabetes mellitus. Administration of L-arginine and its combination with L-carnitine caused an increase in the production NO metabolites and eNOS expression levels by 2.13 and 3.8 times, respectively. In parallel, improvement in the electrolyte excretory function of the kidneys, an increase in the Na,K-ATPase activity in organ homogenates, and a decrease in organ-specific enzymes in blood plasma were observed, which indicates the effectiveness of the correction of the identified violations. A way to eliminate metabolic and functional disorders with combinations of L-arginine and L-carnitine is pathogenetically substantiated. This methodological approach can be recommended for the prevention of microvascular complications in patients with type 1 diabetes mellitus.