Peculiarities of acid-releasing renal function of rats in the dynamics of experimental diabetes mellitus with underlying pharmacological blockade of renin-angiotensin-aldosterone system


Keywords: experimental diabetes mellitus, alloxan, captopril, acid-releasing renal function, renin-angiotensin-aldosterone system.

Abstract

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.

References

1. Denysenko, V. P. (2010). Vmist aldosteronu u khvorykh na diabetychnu nefropatiiu z arterialnoiu hipertenziieiu [Aldosterone levels in the patients with diabetic nephropathy and arterial hypertension]. Ukrainskyi terapevtychnyi zhurnal – Ukrainian Therapeutical Journal, 2, 51–54. Vziato z http://www.vitapol.com.ua/user_files/pdfs/utj/17049613921586_20092010112301.pdf

2. Kayukov, I. G., Dobronravov, V. A., Kucher, A. G., Esayan, A. M., & Smirnov, A. V. (2013). Pochechnye tubulyarnye atsidozіv praktike “Vzroslogo” nefrologa. Soobshchenie І. Rol' pochek v regulyatsii kislotno-osnovnogo gomeostaza [Renal tubular acidosis in practice of “adult” nephrologist. Communication I. Kidneys role in acid base homeostasis regulation]. Nefrologiya – Nephrology, 17 (1), 20–41. Vzyato s https://cyberleninka.ru/article/n/pochechnye-tubulyarnye-atsidozy-v-praktike-vzroslogo-nefrologa-soobschenie-1-rol-pochek-v-regulyatsii-kislotno-osnovnogo-gomeostaza

3. Mahalias, V. M., Mikhieiev, A. O., Rohovyi, Yu. Ye., Shcherbinina, A. V., Turchynets, T. H., & Chipko, T. M. (2001). Suchasnі metodiki eksperimental'nikh ta klіnіchnikh doslіdzhen' tsentral'noї naukovo-doslіdnoї laboratorії Bukovins'koї derzhavnoї medichnoї akademії [Modern methods of experimental and clinical studies of the central research laboratory of Bukovinian State Medical Academy]. Navchal'no-metodichniy posіbnik. – Chernіvtsі: Bukovins'ka derzhavna medichna akademіya.

4. Natochin, Yu. V. (1982). Osnovy fiziologii pochki [Fundamentals of Kidney Physiology]. L.: Meditsina.

5. Rebrova, O. Yu. (2002). Statisticheskiy analiz meditsinskikh dannykh. Primenenie paketa prikladnykh programm STATISTICA [Statistical analysis of medical data. Application of the STATISTICA software package]. M.: MediaSfera.

6. Ryabov, S. I., Natochin, Yu. V. (1997). Funktsional'naya nefrologiya [Functional Nephrology]. Spb.: Lan'.

7. Khraychik, D. E., Sedor, Dzh. R., & Gants, M. B. (2001). Sekrety nefrologii [Nephrology Secrets]. Spb.: “Izdatel'stvo BINOM” – “Nevskiy Dialekt”. ISBN 5-7940-0075-9

8. Shestakova, M. V. (2010). Rol' tkanevoy renin-angiotenzin-al'dosteronovoy sistemy v razvitii metabolicheskogo sindroma, sakharnogo diabeta i ego sosudistykh oslozhneniy (plenarnaya lektsiya) [The role of the tissue renin-angiotensin-aldosterone system in the development of metabolic syndrome, diabetes mellitus and its vascular complications (plenary lecture)]. Sakharnyy diabet – Diabetes Mellitus, 3, 14–19. Vzyato s https://www.dia-endojournals.ru/jour/article/viewFile/5481/3279

9. Shyuk, O. (1981). Funktsional'noe issledovanie pochek [Examination of kidney function]. Praga: Avitsenum.

10. Boychuk, T. M., Olenovych, O. A., & Gozhenko, A. I. (2016). Peculiarities of ionoregulatory renal function disorder in case of diabetes mellitus. Pharmacologyonline, 3, 1–5. Retrieved from http://dspace.bsmu.edu.ua:8080/xmlui/handle/123456789/13523

11. Boychuk, T. M., Olenovych, O. A., & Gozhenko, A. I. (2018). Peculiarities of excretory renal function in the early period of alloxan-induced experimental diabetes. Visnyk morskoi medytsyny – Bulletin of Marine Medicine, 3 (80), 102–109. doi: http://dx.doi.org/10.5281/zenodo.1450849

12. Brown, D., Carsten, A. & Wagner, C. A. (2012). Molecular Mechanisms of Acid-Base Sensing by the Kidney. Journal of the American Society of Nephrology, 23, 774–780. doi: 10.1681/ASN.2012010029

13. Nagami, G. T., & Kraut, J. A. (2010). Acid–base regulation of angiotensin receptors in the kidney. Current Opinion in Nephrology and Hypertension, 19, 91–97. doi:10.1097/MNH.0b013e32833289fd

14. Weiner, D. I., & Verlander, J. W. (2011). Role of NH3 and NH4+ transporters in renal acid-base transport. American Journal of Physiology: Renal Physiology 300, F11–F23. doi:10.1152/ajprenal.00554.2010

15. Weiner, D. I., & Verlander, J. W. (2013). Renal Ammonia Metabolism and Transport. Comprehensive Physiology, 3 (1), 201–220. doi:10.1002/cphy.c120010

16. Weiner, D. I., & Verlander, J. W. (2019). Emerging Features of Ammonia Metabolism and Transport in Acid-Base Balance. Seminars in Nephrology, 39 (4), 394–405. doi:10.1016/j.semnephrol.2019.04.008

17. Yamazaki, O., Ishizawa, K., Hirohama, D., Fujita, T., & Shibata, S. (2018). Electrolyte transport in the renal collecting duct and its regulation by the renin-angiotensin-aldosterone system. Clinical Science, 133, 75–82. https://doi.org/10.1042/CS20180194
Published
2020-10-12
How to Cite
OlenovychО. (2020). Peculiarities of acid-releasing renal function of rats in the dynamics of experimental diabetes mellitus with underlying pharmacological blockade of renin-angiotensin-aldosterone system. Reports of Vinnytsia National Medical University, 24(3), 381-388. https://doi.org/https://doi.org/10.31393/reports-vnmedical-2020-24(3)-02