Filipets N. Experimental study of nephroprotective activity of potassium and calcium channel modulators under conditions of acute and chronic kidney injury

The dissertation is dedicated to investigation of nephroprotective properties of fluorine-containing adenosine triphosphate-sensitive potassium channels activator flocalin in comparison to renal effects of benzothiazepine calcium channel blocker diltiazem under the conditions of acute and chronic renal injury. On the models of sublimate nephropathy with the primary damage of proximal part of nephron and further lesion of glomerular processes flocalin demonstrates protective effects in both glomerular and tubular parts of the nephron. On the stage of hypoxic histohemic nephropathy with the injury of proximal and distal parts of nephron the protective properties of flocalin including its antiproteinuric action prevail over the effect of diltiazem (5 mg per kg, intraventricularly). Under the influence of flocalin the activity of alkaline phosphatase and succinate dehydrogenase in renal tissues increased. We have found that in comparison to diltiazem flocalin shows more pronounced regulatory effects on energetic metabolism, the processes of unrestricted proteolysis, collagenosis, fermentative fibrinolysis, which restrict the destruction of nephrocytes and lead to positive structural reconstruction of kidneys. The presence of protective influence on vascular-glomerular and cellular-tubular levels gives evidence that ATP-sensitive potassium channels activator has universal pharmacodynamics and it can be referred to as a perspective nephroprotective agent for a wide range of renal diseases with the lesion of glomerular filtration and tubular reabsorbtion as the main pathogenetic mechanisms.