2-ETHYLTHIOBENZIMIDAZOLE HYDROBROMIDE PREVENTS A DECREASE IN CORONARY VASCULAR TONE AND MYOCARDIAL CONTRACTILITY IN RATS WITH EXPERIMENTAL DIABETES MELLITUS

Abstract

Objectives. To assess the possibility of preventing the disturbances of coronary vascular tone and myocardial contractile function caused by diabetes mellitus with the help of 2-ethylthiobenzimidazole hydrobromide. Material and methods. Coronary vascular tone and myocardial contractile function were studied on preparations of rat hearts isolated by the Langendorff method. The iNOS blockade was carried out with S-methylisothiourea (S-MT, 10-6M). Diabetes mellitus in rats was modelled by means of a single intraperitoneal injection of streptozocin (50 mg / kg). 2-ethylthiobenzimidazole hydrobromide (2-ETG) was injected intraperitoneally at a dose of 3 mg / kg. The concentration of stable degradation products of NO (NO2-/NO3-), superoxide dismutase, catalase, diene conjugates and malondialdehyde in the left ventricular homogenate was determined by spectrophotometric method. The content of inducible and endothelial NO-synthases (eNOS), interleukin 1β, C-reactive protein in the blood serum of experimental animals was determined by enzyme immunoassay. Results. In the hearts of «2-ETG + Diabetes mellitus» animal group no changes in the coronary perfusion pressure and developed intraventricular pressure were observed before and after the use of the highly selective iNOS blocker S-methylisothiourea. In the blood serum of these animals group, an increase in the concentration of eNOS was observed, against the background of a decrease in the accumulation of iNOS, a decrease in the concentration of lipid peroxidation products was determined against the background of an increase in the activity of the antioxidant system and a decrease of systemic inflammation. Conclusions. Intraperitoneal injection of 2-ethylthiobenzimidazole hydrobromide prevents a decrease in coronary vascular tone and myocardial contractile function caused by hyperproduction of nitrogen monoxide of inducible NO-synthase in diabetes mellitus. This effect of 2-ethylthiobenzimidazole hydrobromide is associated with: limiting the formation of oxidative stress; limiting the nitrosative stress; the decrease in the concentration of inflammatory markers.