System of the ATP-dependent potassium channels (K ATP ) is an important endogenous mechanism of organism protection against ischemia and hypoxia, arousing an interest in search and study of the pharmacological activators of potassium current. Review is devoted to a generalized scientific literary data justifying a wide pharmacodynamical spectrum of flocalin -a potential drug from the class of K ATP -channels activators with its features as a cardioprotector, myotropic spasmolytic, vasodilator and cerebroprotector. Results of own research showing the ability of flocalin to maintain homeostatic functions of kidneys under the conditions of water-salt loading are also represented. Taking into consideration cardiorenal continuum, pathogenetic connection between renal and cardiac pathology makes it possible to suggest an inhibitory influence of flocalin on the development of nephropathy. A prerequisite for a study of its renal effects is data concerning the mechanisms of correction the morphological, functional and biochemical pathological changes in myocardium by flocalin, which allows positioning this new activator of K ATP -channels as a perspective cardioprotector and also may give rise to a new direction in nephroprotection.Nephroprotective properties of atp-sensitive potassium channels agonist flocalin

Экспериментальные модели заболеваний почек для исследований патогенетических механизмов и эффективности фармакологической коррекции на фоне коморбидной патологии Н. Н. Серединская, Н. Д. Филипец, Е. А. Филипец, К. В. Слободян, А. И. Гоженко Цель работы -освещение современных моделей заболеваний почек, сочетанных с другими патологическими состояниями, для экспериментальных исследований патогенетических механизмов и эффективности фармакологической коррекции.Рассмотрены экспериментальные модели, которые целесообразно использовать для исследования патогенеза и эффективности средств фармакологической коррекции коморбидной патологии. Акцентировано внимание на моделях, воспроизводящих кардиоренальный, гепаторенальный синдром и полиорганное гипоксическое гистогемическое повреждение у лабораторных крыс. Эти модели характеризуются легким моделированием, воспроизведением патогенеза коморбидных заболеваний, наличием острого и хронического периода повреждения, индуцированного антибиотиком доксорубицином или экотоксикантами -сулемой, нитритом натрия, 2,4-динитрофенолом.Выводы. Представленные модели кардиоренального, гепаторенального синдромов и гипоксического повреждения организма являются оптимальными для проведения многоцелевых исследований физиологического, патофизиологического, фармакологического направлений с максимальным приближением результатов к клинико-терапевтическим особенностям коморбидной патологии.The aim of our study is to report about modern models of kidney diseases associated with other pathological conditions for experimental studies of pathogenic mechanisms and efficacy of pharmacological correction.The study deals with experimental models reasonably to be applied in investigation of comorbid pathology pathogenesis and efficacy of its pharmacological correction. The attention is focused on the models of cardio-renal, hepatic-renal syndromes and multiple organ hypoxic histochemical injury simulated in laboratory rats. These models are characterized by easy modeling, simulation of comorbidity pathogenesis, acute and chronic periods of diseases available, induced by the antibiotic Doxorubicin or exotoxins -corrosive sublimate, sodium nitrite, and 2,4-dinitrophenol.Conclusions. The models of cardio-renal, hepatic-renal syndromes and hypoxic histochemical injury of the body are found to be optimal to perform multipurpose studies of physiological, pathophysiological, pharmacological directions with maximal similarity of the results obtained to clinical-therapeutic peculiarities of comorbid pathology.Експериментальні моделі захворювань нирок для досліджень патогенетичних механізмів та ефективності фармакологічної корекції на тлі коморбідної патології Н. М. Серединська, Н. Д. Філіпець, О. О. Філіпець, К. В. Слободян, А. І. Гоженко Мета роботи -висвітлення сучасних моделей захворювань нирок, що поєднані з іншими патологічними станами, для експериментальних досліджень патогенетичних механізмів та ефективності фармакологічної корекції.Розглянуті експериментальні моделі, які доцільно використовувати для дослідження пат...

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in the experiments on rats subjected to acute hypoxic histochemical nephropathy, caused by sodium nitrite and 2,4-dinitrophenol, fibrinolytic activities of blood plasma, urine, renal cortex, medulla, and T he essential biochemical characteristic of plasma membranes ATP-sensitive potassium (K ATP ) channels, which are gated by intracellular nucleotides ATP and ADP, is their sensitivity to disturbances in cellular metabolism. Subsequently, rapid activation and opening of K ATP channels in response to the decrease of ATP level, in particular under conditions of ischemia and hypoxia, results in plasma membrane hyperpolarization and the decrease of voltage dependent inflow of Ca 2+ ions. The latter event is accompanied by drastic disturbance of energy metabolism compliance with the functional needs of the cell and initiates the pathological cascades leading to the profound cellular pathology.The regulatory role of K ATP channels in conditions of cellular oxygenation restriction was first studied on cardiomyocytes and smooth muscle cells of blood vessels [1], that resulted in the use of pharmacological activators of these channel types for treatment of cardiovascular diseases. In recent years the convincing evidence of cardioprotective and vasodilatory effects of the original K ATP channels fluoride-containing activator Flocalin -N-(-4-difluoromethoxyphenyl)-N′-1,2,2-trimethylpropyl-N′′-cyanoguanidine [2] were obtained. Owing to the presence of fluoride, flocalin is more selective to K ATP channels and less toxic compared to other representatives of potassium channels modulators that makes it perspective and promising pharmacological substance as physiological regulator and protector of metabolic processes disturbed under hypoxic and ischemic conditions.

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