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Effects of imidazo[1,2-a]azepinie derivative ift_000281 on ATP-dependent potassium channels

Journal: Scientific Herald of Chernivtsi University. Biology (Biological Systems) (Vol.8, No. 1)

Publication Date:

Authors : ; ;

Page : 53-58

Keywords : myocardium preconditioning; ATP-dependent K-channels; isolated heart; ischemia; imidazo[1; 2-a]azepine derivatives;

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Abstract

In this work we have been experimentally tested the ability of imidazo[1,2-a]azepine derivative, compound under IFT_000281 code to activate the ATP-dependent potassium channels (KATP channels). To confirm or refute our hypothesis that the investigated imidazo[1,2-a]azepine derivative is an activator KATP channels, a series of experiments using a blocker of KATP channels glibenclamide was performed. Glibenclamide was added to the perfusion solution at a concentration of 1•10-5 M for 5 minutes before the perfusion of the isolated heart by solution of the same concentration of IFT_000281. If IFT_000281 substance activates KATP channels of cardiomyocytes preliminary action of glibenclamide will neutralize its effects. As a result of studies, it was found that the preliminary action of glibenclamide on isolated rat heart eliminates cardioprotective effects of the compound IFT_000281 at a concentration of 1•10-5 M. Thus, using without glibenclamide, IFT_000281 causes an increase of pressure in the left ventricle by 43%, the speed of contraction and relaxation of the myocardium – in 75% and 53% respectively. Coronary blood flow speed increased in 38% and the time until cardiac arrest increases in 33% compared to control values. After pretreatment with glibenclamide, there was not statistically significant change in performance under the influence of investigated compounds IFT_000281. These values were not different from controls. Analyzing the results and considering the known fact, that glibenclamide is a selective blocker of KATP channels, it can be argued that the compound IFT_000281 acts on the ATP-dependent K-channels and this causes its cardioprotective properties.

Last modified: 2017-06-30 03:10:03