Renin-angiotensin system in the regulation of renal excretory function in case of experimental diabetes mellitus

Main Article Content

О.А. Olenovych


Background. The purpose of the study was to explore the role of the renin-angiotensin system in the disturbance of renal excretory function in the dynamics of alloxan-induced experimental diabetes mellitus. Materials and methods. The experiments were carried out on 78 white non-linear mature male rats with 11-, 26- and 46-day long experimental diabetes mellitus caused by intraperitoneal administration of alloxan (160 mg/kg), against the background of pharmacological blockade of intrarenal renin-angiotensin system, induced by intraperitoneal administration of сaptopril (10 mg/kg). The study of excretory function of the kidneys was provided by the clearance method under the condition of induced water 2-hour diuresis to determine the clearance of endogenous creatinine, glomerular filtration rate, relative water reabsorption, protein content in urine, its excretion. Results. Analysis of changes in renal function after pharmacological blockade of the renin-angiotensin system in rats on day 11 of alloxan diabetes showed a significant increase in diuresis, glomerular filtration rate, endogenous creatinine concentration index, and protein excretion. The pharmacological blockade of the renin-angiotensin system had practically no effect on the intensity of the relative reabsorption of water in alloxan-diabetic rats. On day 26 of alloxan diabetes after captopril administration, there was a slight decrease in final urine volume, glomerular filtration rate, relative water reabsorption, and endogenous creatinine concentration index. At the same time, captopril did not cause an antiproteinuric effect, and protein excretion even demonstrated a tendency to increase. On day 46 of alloxan-induced diabetes after administration of captopril, there was a significant reduction in diuresis, endogenous creatinine clearance and glomerular filtration rate of rats, as well as in urinary protein concentration and excretion. Conclusions. The results of the study allow us to conclude that the initial stage of renal disorders formation in alloxan-induced experimental diabetes is associated with hemodynamic-hyperperfusion nature of renal functioning with preserved renal functional reserve and the structure of the glomerular-tubular apparatus of the kidney, autoregulatory mechanisms. Mentioned compensatory-functional changes in renal function are gradually complicated by an exhaustion of renal functional reserve and pathological activation of intrarenal renin-angiotensin system with subsequent progression of hyperperfusion-ischemic kidney damage, a decrease in the number of functioning nephrons.

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How to Cite
Olenovych О. “Renin-Angiotensin System in the Regulation of Renal Excretory Function in Case of Experimental Diabetes Mellitus”. INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine), vol. 16, no. 8, Aug. 2021, pp. 636-42, doi:10.22141/2224-0721.16.8.2020.222880.
Original Researches


Radchenko GD, Torbas OO, Sirenko YM. Predictors of high central blood pressure in young with isolated systolic hypertension. Vasc Health Risk Manag. 2016 Aug 2;12:321-328. doi:10.2147/VHRM.S97304.

Meyrier A. Nephrosclerosis: a term in quest of a disease. Nephron. 2015;129(4):276-282. doi:10.1159/000381195.

Tomino Y. Pathogenesis and treatment of chronic kidney disease: a review of our recent basic and clinical data. Kidney Blood Press Res. 2014;39(5):450-489. doi:10.1159/000368458.

Cerquozzi S, Tefferi A. Blast transformation and fibrotic progression in polycythemia vera and essential thrombocythemia: a literature review of incidence and risk factors. Blood Cancer J. 2015 Nov 13;5(11):e366. doi:10.1038/bcj.2015.95.

Meyer KC. Diagnosis and management of interstitial lung disease. Transl Respir Med. 2014 Feb 13;2:4. doi:10.1186/2213-0802-2-4.

Hannedouche T, Krummel T, Parvez-Braun L. Nephroprotection: how to slow the progression of chronic renal insufficiency? Nephrol Ther. 2005 May;1(2):135-144. doi:10.1016/j.nephro.2005.05.003. (in French).

Atlas SA. The renin-angiotensin aldosterone system: pathophysiological role and pharmacologic inhibition. J Manag Care Pharm. 2007 Oct;13(8 Suppl B):9-20. doi:10.18553/jmcp.2007.13.s8-b.9.

Park YS. Renal scar formation after urinary tract infection in children. Korean J Pediatr. 2012 Oct;55(10):367-370. doi:10.3345/kjp.2012.55.10.367.

Ihm CG. Hypertension in Chronic Glomerulonephritis. Electrolyte Blood Press. 2015 Dec;13(2):41-45. doi:10.5049/EBP.2015.13.2.41.

Sulaiman MK. Diabetic nephropathy: recent advances in pathophysiology and challenges in dietary management. Diabetol Metab Syndr. 2019 Jan 23;11:7. doi:10.1186/s13098-019-0403-4.

Alicic RZ, Rooney MT, Tuttle KR. Diabetic Kidney Disease: Challenges, Progress, and Possibilities. Clin J Am Soc Nephrol. 2017 Dec 7;12(12):2032-2045. doi:10.2215/CJN.11491116.

Briukhanov VM, Zverev YaF, Lampatov VV, Zharikov AYu. Methodical approaches to the study of renal function in animal experiments. Nephrology (Saint-Petersburg). 2009;13(3):52-62. doi:10.24884/1561-6274-2009-13-3-52-62. (in Russian).

Modern methods of experimental and clinical studies of the central research laboratory of Bukovinian State Medical Academy. Chernivtsi; 2001. 42 p. (in Ukrainian).

Pressler BM. Clinical approach to advanced renal function testing in dogs and cats. Vet Clin North Am Small Anim Pract. 2013 Nov;43(6):1193-208, v. doi:10.1016/j.cvsm.2013.07.011.

Boychuk TM, Olenovych OA, Gozhenko AI. Peculiarities of excretory renal function in the early period of alloxan-induced experimental diabetes. Visnyk mors'koi' medycyny. 2018;3(80):102-109. doi:10.5281/zenodo.1450849.

Fu H, Liu S, Bastacky SI, Wang X, Tian XJ, Zhou D. Diabetic kidney diseases revisited: A new perspective for a new era. Mol Metab. 2019 Dec;30:250-263. doi:10.1016/j.molmet.2019.10.005.

Lin YC, Chang YH, Yang SY, Wu KD, Chu TS. Update of pathophysiology and management of diabetic kidney disease. J Formos Med Assoc. 2018 Aug;117(8):662-675. doi:10.1016/j.jfma.2018.02.007.

Li L, Chen L, Zang J, et al. C3a and C5a receptor antagonists ameliorate endothelial-myofibroblast transition via the Wnt/β-catenin signaling pathway in diabetic kidney disease. Metabolism. 2015 May;64(5):597-610. doi:10.1016/j.metabol.2015.01.014.

Bomsztyk K, Denisenko O, Wang Y. DNA methylation yields epigenetic clues into the diabetic nephropathy of Pima Indians. Kidney Int. 2018 Jun;93(6):1272-1275. doi:10.1016/j.kint.2018.02.015.

Colombo M, Looker HC, Farran B, et al. Serum kidney injury molecule 1 and β2-microglobulin perform as well as larger biomarker panels for prediction of rapid decline in renal function in type 2 diabetes. Diabetologia. 2019 Jan;62(1):156-168. doi:10.1007/s00125-018-4741-9.