Benzimidazole Derivative, 2-ETH Prevents Poststressor Disorders of Coronary Vascular Tone and Myocardial Contractility

Introduction. Due to unpredictability of stressors exposure, prevention of stress-induced coronary vascular tone disorders with new classes of drugs with pleiotropic action is quite relevant. At the present time, besides traditionally used vasoactive substances, benzimidazole derivatives with antioxidant and anti-inflammatory activity are considered. The goal of the present study is to test the hypothesis that infusion of the 2-ethyl-thiobenzimidazole hydrobromide (2-ETH) before stress is able to effectively prevent stress-induced disorders of coronary vascular tone and myocardial contractility disorders and clarify mechanisms of such 2-ETH action. Materials and methods. Coronary vascular tone and myocardial contractility were investigated using Langendorff isolated rat heart model. The ВКСа-channel inhibitor, tetraethylammonium (TEA) was added to the Krebs-Henseleit solution to the final concentration of 1 mM. Concentration of the stable products of NO degradation (NO2-/NO3-) was determined spectrophotometrically; activation of lipid peroxidation was assessed in the myocardium using a spectrophotometric method; concentration of iNOS, еNOS, and IL-1β was detected with enzyme-linked immunosorbent assay; concentration of C-reactive protein was estimated with immunoturbidimetric method. Results. 2-ETH pretreatment prevented stress-induced decrease in ВКСа-channels and eNOS activity, limited iNOS activity in coronary vessels and restored myocardial contractility. These 2-ETH’ effects together with its ability to prevent alterations of stress-sensitive organs and limit oxidative, nitrozative stress and systemic inflammation argue why 2-ETH should be considered as a useful tool for pathogenetic prevention of stress-induced pathology. Conclusions. 2-ETH should be considered as a useful tool for pathogenetic prevention of stress-induced pathology.

2-ethyl-thiobenzimidazole hydrobromide, lipid peroxidation, coronary vessels’ tone, NO-synthase, ВК_Сa-channels

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