MINERALOCORTICOID RECEPTOR BLOCKADE AFFECTING THE ADAPTATION STRATEGY OF RATS WITH DIFFERENT STRESS RESISTANCE IN THE POST-TRAUMATIC PERIOD AFTER MYOCARDIAL CONTUSION

The study aims to evaluate the eff ect of mineralocorticoid receptor blockade on the adaptation strategy of rats with diff erent stress resistance in the post-traumatic period after myocardial contusion. Materials and methods. The stress resistance of rats was evaluated with the Porsolt forced swimming test and open fi eld test. Each category of rats (low-, medium- and high-resistant) was divided into three groups: control, myocardial contusion, heart contusion + eplerenone. The myocardial contusion was simulated using the original device. Prior to injury simulation, rodents received eplerenone injection for 10 days at a dose of 100 mg/kg/day. 24 hours after simulating myocardial contusion and in the control testing, rectal temperature was measured, levels of corticosterone, total protein, albumins, triglycerides, glucose, lactic acid were determined in the blood, the total number of leukocytes, white blood cell count and leukocyte indices were calculated. The total antioxidant capacity and the level of reduced glutathione were determined in the myocardial tissue. Statistical data processing was carried out using methods of descriptive statistics and sample comparison (Mann–Whitney U test). The level of statistical signifi cance is assumed to be 0.05. Data processing was carried out with IBM SPSS Statistics 23. Results. In comparison with the group without pharmacological treatment, low- and medium-resistant rats treated with eplerenone were recorded with signifi cantly lower level of corticosterone, triglycerides, glucose, and lactic acid in blood plasma, as well as higher values of the total antioxidant capacity and the level of reduced glutathione in the myocardium in the post-traumatic period after myocardial contusion. The total number of leukocytes, the percentage of segmented, band neutrophils and the nuclear shift index in rodents treated with eplerenone were statistically signifi cantly lower compared with the other group. The described eff ects of eplerenone are most likely implemented via the direct cardioprotective eff ect related to a decrease in the production of free radicals, and mediated by a decrease in heart pre- and afterload.

1. Приймак А. Б., Корпачева О. В., Золотов А. Н., Новиков Д. Г. Стратегии адаптации при ушибе сердца у крыс с различной стрессоустойчивостью // Вестник СурГУ. Медицина. 2021. № 4. С. 110–116.

2. Y uyun M. F., Jutla S. K., Quinn P. A., Ng L. L. Aldosterone Predicts Major Adverse Cardiovascular Events in Patients with Acute Myocardial Infarction // Heart Asia. 2012. Vol. 4, Is. 1. P. 102–107.

3. Sztechman D., Czarzasta K., Cudnoch-Jedrzejewska A., Szczepanska Sadowska E., Zera T. Aldosterone and Mineralocorticoid Receptors in Regulation of the Cardiovascular System and Pathological Remodelling of the Heart and Arteries // J Physiol Pharmacol. 2018. Vol. 69, Is. 6. P. 829–845.

4. Dragasevic N., Jakovljevic V., Zivkovic V. et al. The Role of Aldosterone Inhibitors in Cardiac Ischemia-Reperfusion Injury // Can J Physiol Pharmacol. 2021. Vol. 99, No. 1. P. 18–29. DOI 10.1139/ cjpp-2020-0276.

5. Van den Berg T. N. A., Rongen G. A., Fröhlich G. M. et al. The Cardioprotective Effects of Mineralocorticoid Receptor Antagonists // Pharmacol Ther. 2014. Vol. 142, Is. 1. P. 72–87. DOI 10.1016/j. pharmthera.2013.11.006.

6. Савенко И. А., Усманский Ю. В., Ивашев М. Н., Сергиенко А. В., Лысенко Т. А., Куянцева А. М., Арльт А. В., Зацепина Е. Е., Саркисян К. Х., Ефремова М. П., Шемонаева М. В. Возможность применения ветеринарного препарата в экспериментальной фармакологии // Фундаментальные исследования. 2012. № 5–2. С. 422–425. URL: https://fundamental-research.ru/ru/article/view?id=29949 (дата обращения: 23.06.2022).

7. Липат ов а А. С., Поляков П. П., Каде А. Х., Трофименко А. И., Кравченко С. В. Влияние транскраниальной электростимуляции на выносливость крыс с разной устойчивостью к стрессу // Биомедицина. 2018. № 1. С. 84–91.

8. Гостюхин а А. А., Замощина Т. А., Прокопова А. В., Зайцев К. В. Индивидуально-типологические особенности реагирования лабораторных крыс на многокомпонентный стресс // Современные вопросы биомедицины. 2022. Т. 6, № 2 (19). URL: https:// doi: 10.51871/2588-0500_2022_06_02_5 (дата обращения: 23.06.2022).

9. Приймак А. Б. Сочетанное применение поведенческих тестов при оценке стрессоустойчивости лабораторных животных // Молодежь. Наука. Творчество : материалы XIX Всероссийской науч.-практич. конф. (Омск, 09–11 ноября 2021 г.). Омск : Омск. гос. технич. ун-т, 2021. С. 60–64.

10. Долгих В. Т., Корпачева О. В., Ершов А. В. Способ моделирования ушиба сердца у мелких лабораторных животных (полезная модель) : пат. 37427 Рос. Федерация : МПК7 G 09B9/00 ; заявитель и патентообладатель Омская гос. мед. акад. № 2003133897/20 (036729) ; заявл. 24.11.03 ; опубл. 20.04.04. Бюл. № 11.

11. Пахрова О. А., Криштоп В. В., Курчанинова М. Г., Румянцева Т. А. Лейкоцитарные показатели крови при адаптации к острой экспериментальной гипоксии головного мозга в зависимости от уровня стрессоустойчивости // Современные проблемы науки и образования. 2016. № 6. С. 231.

12. Reddy N. M ., Mahajan U. B., Patil C. R. et al. Eplerenone Attenuates Cardiac Dysfunction and Oxidative Stress in β-Receptor Stimulated Myocardial Infarcted Rats // Am J Transl Res. 2015. Vol. 7 (9). P. 1602–1611.

13. Mahajan U. B., Patil P. D., Chandrayan G. et al. Eplerenone Pretreatment Protects the Myocardium against Ischaemia/

14. Reperfusion Injury Through the Phosphatidylinositol 3-Kinase/Akt-Dependent Pathway in Diabetic Rats // Mol Cell Biochem. 2018. Vol. 446. P. 91–103. DOI 10.1007/s11010-018-3276-1.

15. Зверев Я. Ф., Брюханов В. М. О функциональной роли центральных минералокортикоидных рецепторов и возможностях их фармакологической регуляции // Нефрология. 2006. № 10 (1). С. 14–24. URL: https://cyberleninka.ru/article/n/o-funktsionalnoyroli-tsentralnyhmineralokortikoidnyh-retseptorov- i -vozmozhnostyah-ih-farmakologicheskoy-regulyatsii (дата обращения: 13.05.2022).

16. Drobysheva A., Ahmad M., White R., Wang H.-W., Leenen F. H. H. Cardiac Sympathetic Innervation and PGP9.5 Expression by Cardiomyocytes after Myocardial Infarction: Effects of Central MR Blockade // Am J Physiol Heart Circ Physiol. 2013. Vol. 305, Is. 12. P. H1817–H1829. DOI 10.1152/ajpheart.00445.2013.

17. DuPont J. J., Jaffe I. Z. 30 Years of Mineralocorticoid Receptor: The Role of the Mineralocorticoid Receptor in the Vasculature // J Endocrinol. 2017. Vol. 234, Is. 1. P. T67–T82. DOI 10.1530/JOE-17-0009.

18. Schmidt K., Tissier R., Ghaleh B. et al. Cardioprotective Effects of Mineralocorticoid Receptor Antagonists at Reperfusion // Eur Heart J. 2010. Vol. 31, Is. 13. P. 1655–1662. DOI 10.1093/eurheartj/ehp555.

19. Zafir A., Banu N. Modulation of In Vivo Oxidative Status by Exogenous Corticosterone and Restraint Stress in Rats // Stress. 2009. Vol. 12, Is. 2. P. 167–177.

20. Fraccarollo D., Thomas S., Scholz C. J. et al. Macrophage Mineralocorticoid Receptor Is a Pleiotropic Modulator of Myocardial Infarct Healing // Hypertension. 2019. Vol. 73, Is. 1. P. 102–111. DOI 10.1161/HYPERTENSIONAHA.118.12162.