Effect of Hyperglycemia on Oscillations in Calcium and Nitric Oxide Concentrations in Mouse Skin Endotheliocytes

The most complications of diabetes mellitus are associated with endothelial dysfunction, the nature of which is not fully understood. Oscillations of calcium (Ca²⁺) and nitric oxide (NO) concentrations may play a role in regulating endothelial functioning under normal and pathological conditions. We suHGested that changes of Ca²⁺ and NO oscillations characteristics in endothelial cells may play a role in the pathogenesis of diabetes mellitus complications. To test this hypothesis, we assessed the dependence on the glucose concentration (normo- and hyperglycemia) of the amplitude-frequency characteristics of Ca²⁺ and NO oscillations in endothelial cells from mouse skin microvessels at rest and during functional tests (heating), the effect of the vasodilator acetylcholine (ACh), insulin, as well as when blocking NOS and PI3K. Hyperglycemia changes the amplitude-frequency characteristics of Ca²⁺ and NO oscillations in endotheliocytes and the proportion of cells with oscillations. In addition, hyperglycemia changes the characteristics of Ca²⁺ and NO oscillations in endothelial cells in presence of ACh, L-NNA, wortmannin and insulin at rest (37 °C) and heating to 40 °C. It indicates the participation of TRPV-, NOS-, ACh- and PI3K-associated signaling pathways in the regulation of Ca²⁺ and NO oscillations in endoteliocytes in health and disease.