The role of adipose tissue cell elements in the regulation of the nitroxidergic system and possible ways of pharmacological modulation

Abstract

Endothelial dysfunction is characterized by a decrease in the bioavailability of the vasodilator – nitric oxide (NO), and an increase in the level of vasoconstrictor substances. This imbalance leads to vasoconstriction, leukocyte attachment and inflammatory reactions in the vascular wall, atherosclerosis and thrombosis. The aim: to evaluate the role of adipose tissue elements in the regulation of parameters of the nitroxidergic system under hypoxia conditions. Materials and methods. The studies were carried out on 30 adult white male Wistar rats. All animals were randomly assigned and divided into groups: a control group (15 rats), type 2 diabetes mellitus (T2DM) was induced in the animals of the second group (15 rats). Isolated fragments of the popliteal arteries (PA) and intrapulmonary artery (IPA) were cleared of perivascular adipose tissue (PVAT-) or left uncleaned (PVAT+) and cut into rings. The simulation of acute hypoxia with further study of medical agents were performed. Results. The PA and IPA with PVAT responded to acute hypoxia with vasoconstriction – an increase in the amplitude of contraction in the first and second phases, and after removing PVAT, they responded with a decrease in the maximum amplitude of contraction by 3.4 times in the 1st phase and an increase in amplitude by 1.8 times in the 2nd phase. Perfusion with Angiolin reduced 2nd phase of HV of the PA and IPA. Adding a combination of Thiotriazoline and L-arginine (1:4) to a solution for perfusion of fragments of arteries of animals with T2DM, causes a significant increase in constrictor reactions in both the 1st and 2nd phases of HV, regardless of presence of perivascular adipose tissue. Conclusions. The presence of PVAT affects the HV of arteries, both in normal and in T2DM. The possibilities of ways of pharmacological modulation of the nitroxidergic system depending on the state of PVAT were determined.

Keywords

• vasoconstriction
• pulmonary artery
• type 2 diabetes mellitus
• nitrosative stress
• enos
• inos
• thiotriazoline
• angioline
• combination of thiotriazoline and l-arginine (1:4)
• endothelial protection