Peculiarities of acid-releasing renal function of rats in the dynamics of experimental diabetes mellitus with underlying pharmacological blockade of renin-angiotensin-aldosterone system
Annotation. The aim of the study was to explore the peculiarities of acid-releasing renal function of rats in the dynamics of alloxan-induced experimental diabetes mellitus (EDM) with underlying pharmacological blockade of the renin-angiotensin-aldosterone system (RAAS). The experiments were carried out on 78 white non-linear mature male rats with 11-, 26- and 46-day long alloxan-induced EDM with underlying pharmacological blockade of RAAS by administration of captopril. The study of acid-releasing renal function was provided under the condition of water 2-hour diuresis by changes in urine pH, excretion of titrated acids (TA), ammonia and active hydrogen ions with calculations of their excretion and ratio indices, standardization per 100 μl of glomerular filtrate (GF) volume. It was found that after administration of captopril to rats with 11-day long EDM urine pH, excretion of active hydrogen ions, ammonia excretion increased, TA excretion reduced, including it standardized by the volume of GF, as well as standardized excretion of ammonium compounds. After captopril administration to the animals with a 26-day long EDM, urine pH and TA excretion raised, and the excretion of ammonium and hydrogen ions decreased, still exceeding the control values. Standardized by GF, these indices changed similarly. After pharmacological blockade of RAAS on the 46th day of EDM urine pH, TA excretion, including it standardized by GF, excretion of hydrogen ions enhanced. Excretion of ammonium compounds, including it standardized by GF, and standardized excretion of hydrogen ions declined as compared with control parameters. Thus, the intensification of acid-release at the early stages of EDM is systemic by character and develops due to glomerular hyperfiltration, overload of the nephron with acidic products of metabolism and accompanied by structural intactness of the tubular apparatus of the kidneys. Prolonged glomerular hyperfiltration, probably, is the initiating damaging factor for the tubular apparatus of the diabetic kidney, which in 26-day long EDM is accompanied by the inability of enzyme systems of tubular epithelial cells of proximal tubules, mostly, to provide adequate ammoniogenesis, despite the high efficacy of renal transport mechanisms of acid-release. Proximal tubulopathy on the background of augmented aciduria in animals with 46-day long EDM causes relative functional insufficiency of the distal tubular apparatus.
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