Effect of chronic predatory stress on rat liver microcirculation

Introduction. One of the topical issues of modern circulatory physiology is the study of the peculiarities of the influence of chronic stress on the hepatic hemodynamics. The effect of stress on the liver microvessels has not been practically studied.

The aim was to study the parameters of liver microcirculation in rats when modeling chronic stress.

Materials and methods. The study was conducted on 60 male Wistar rats weighing 220-370 g, divided into control and experimental groups of 30 rats each. In animals of the experimental group, chronic predatory stress was simulated by exposure to predator (cat) urine smell for 10 days according to the method of V. E. Zeilikman et al. (2021). Median laparotomy was performed under anesthesia with Zoletil and Xylazine. The study of rat liver microcirculation was performed using laser Doppler flowmeter LAKK-02 (Russia) on the visceral surface of the liver. The study of liver tissue perfusion parameters was carried out before and after stress modelling in rats of the experimental group, before and after laparotomy in rats of the control group (falsely operated animals). Digital data were processed by methods of variation statistics.

Results. When modeling chronic emotional stress, a decrease in the basic microcirculation parameters on the visceral surface of the liver was revealed: microcirculation index – by 28.35 %, coefficient of variation – by 55.92 %, which is probably due to vasoconstriction of the vessels of the microcirculatory link. To the greatest extent, there was a decrease in the mean square deviation (by 100 %), which indicates the deterioration in the mechanisms of modulation of liver tissue perfusion.

Conclusion. Chronic stress has a significant effect on the microcirculation system of the rat liver, which is manifested by a marked decrease in the basic parameters of tissue perfusion and a reduction in the mechanisms of blood flow modulation.

1. Ding Y, Wang K, Xu C, Hao M, Li H, Ding L. Intestinal Claudin-7 deficiency impacts the intestinal microbiota in mice with colitis. BMC Gastroenterol. 2022;22(1):24. Doi: 10.1186/s12876-022-02100-8.

2. Sánchez-Valle V, Chávez-Tapia NC, Uribe M, MéndezSánchez N. Role of oxidative stress and molecular changes in liver fibrosis: a review. Curr Med Chem. 2012;19(28):4850- 4860. Doi: 10.2174/092986712803341520.

3. Konstandi M. Psychophysiological stress: a significant parameter in drug pharmacokinetics. Expert Opin Drug Metab Toxicol. 2013;9(10):1317-1334. Doi: 10.1517/17425255.2013.816283.

4. Liu YZ, Chen JK, Zhang Y, Wang X, Qu S, Jiang CL. Chronic stress induces steatohepatitis while decreases visceral fat mass in mice. BMC Gastroenterol. 2014;14:106. Doi: 10.1186/1471-230X-14-106.

5. Chkhaidze IZ. Gender specificity of reactivity rat skins microvessels according to laser doppler flowmetry. Regional blood circulation and microcirculation. 2022;21(4):58-66. (In Russ.). Doi: 10.24884/1682-6655-2022-21-4-58-66.

6. Yuan X, Wu Q, Shang F, Li B, Liu M, Wang B, Sheng Y, Zhang H, Xiu R. A comparison of the cutaneous microvascular properties of the Spontaneously Hypertensive and the Wistar-Kyoto rats by Spectral analysis of Laser Doppler. Clin Exp Hypertens. 2019;41(4):342-352. Doi: 10.1080/10641963.2018.1481424.

7. Pugach VA, Chefu SG, Tyunin МA, Strokina EI, Faizullina DR, Petrishchev NN. Experimental evaluation of parameters of capillary blood flow, hemorheology and hemostasis on a model of acute respiratory distress syndrome in rats. Regional blood circulation and microcirculation. 2023;22(3):86-95. (In Russ.). Doi: 10.24884/1682-6655-2023-22-3-86-95.

8. Protsak ES, Borshchev YuYu, Galagoudza MM. The role of the main hemodynamic parameters assessing in modern experimental practice. Regional blood circulation and microcirculation. 2023;22(1):103-109. (In Russ.). Doi: 10.24884/1682-6655-2023-22-1-103-109.

9. Belyaeva LE, Pauliukevich HN. The biochemical estimation of the nitric oxide system in prenatally stressed rats. Regional blood circulation and microcirculation. 2021;20(3):61-69. (In Russ). Doi: 10.24884/1682-6655-2021-20-3-61-69.

10. Davies T, Wythe S, O’Beirne J, Martin D, GilbertKawai E. Review article: the role of the microcirculation in liver cirrhosis. Aliment Pharmacol Ther. 2017;46(9):825-835. Doi: 10.1111/apt.14279.

11. Yang YY, Lin HC. Alteration of intrahepatic microcirculation in cirrhotic livers. J. Chin Med Assoc. 2015;78(8):430- 437. Doi: 10.1016/j.jcma.2015.05.005.

12. Alexandrin VV. Wavelet analysis of cerebral blood flow in rats. Regional blood circulation and microcirculation. 2010;9(4):63-66. (In Russ.). Doi: 10.24884/1682-6655-2010-9-4-63-66.

13. Li Z, Tam EW, Kwan MP, Mak AF, Lo SC, Leung MC. Effects of prolonged surface pressure on the skin blood flowmotions in anaesthetized rats - an assessment by spectral analysis of laser Doppler flowmetry signals. Phys Med Biol. 2006;51(10):2681-2694. Doi: 10.1088/0031-9155/51/10/020.

14. Andreeva IV, Telia VD. Peculiarities of skin microcirculation in rats of different sex and age. Siberian J Life Sci Agriculture. 2022;14(1):217-234. (In Russ.). Doi: 10.12731/2658-6649-2022-14-1-217-234.

15. Andreeva IV, Vinogradov AA, Telia VD, Grigorev AS. Indicators of microcirculation in the skin of the abdomen of rats of different genders and ages during a food load test. Crimean J Exp Clin Med. 2022;12(1):16-21. (In Russ.). Doi: 10.37279/2224-6444-2022-12-1-15-20.

16. Andreeva IV, Vinogradov AA, Telia VD, Simakov RYu. Impact of food load test on microcirculation parameters in the liver of rats of different gender and age. Regional hemodynamics and microcirculation. 2022;21(1):71-77. (In Russ.). Doi: 10.24884/1682-6655-2022-21-1-71-77.

17. Sara JDS, Toya T, Ahmad A, Clark MM, Gilliam WP, Lerman LO, Lerman A. Mental Stress and Its Effects on Vascular Health. Mayo Clin Proc. 2022;97(5):951-990. Doi: 10.1016/j.mayocp.2022.02.004.

18. MacCormack JK, Armstrong-Carter EL, GaudierDiaz MM, Meltzer-Brody S, Sloan EK, Lindquist KA, Muscatell KA. β-Adrenergic Contributions to Emotion and Physiology During an Acute Psychosocial Stressor. Psychosom Med. 2021;83(9):959-968. Doi: 10.1097/PSY.0000000000001009.

19. Gebicki J, Katarzynska J, Cholewinski T, Sieron L, Marcinek A. Flowmotion monitored by Flow Mediated Skin Fluorescence (FMSF): a tool for characterization of microcirculatory status. Front Physiol. 2020;11:702. Doi: 10.3389/FPHYS.2020.00702.

20. Tseylikman V.E., Lapshin M.S., Komel′kova M.V. i dr. Sposob modelirovaniya posttravmaticheskogo stressovogo rasstroystva u laboratornykh krys. Rossiyskiy patent 2021 goda po MPK A61B5/16 G09B23/28 G01N33/68 G01N33/74. Appl. 2020120571 06/15/2020.Published: 04/22/2021. (in Russ.).

21. Greaney JL, Surachman A, Saunders EFH, Alexander LM, Almeida DM. Greater daily psychosocial stress exposure is associated with increased norepinephrine‐induced vasoconstriction in young adults. J Am Heart Assoc. 2020; 9(9):e015697. Doi: 10.1161/JAHA.119.015697.

22. Chudzik M, Cender A, Mordaka R, Zielinski J, Katarzynska J, Marcinek A, Gebicki J. Chronic Fatigue Associated with Post-COVID Syndrome versus Transient Fatigue Caused by High-Intensity Exercise: Are They Comparable in Terms of Vascular Effects? Vasc Health Risk Manag. 2022;18:711-719. Doi: 10.2147/VHRM.S371468.

23. Kozlov VI, Sakharov VN, Gurova OA, Sidorov VV. Laser doppler flowmetry assessment of microcirculation in children of 6–7 years old. Regional hemodynamics and microcirculation. 2021;20(3):46-53. (In Russ.). Doi: 10.24884/1682-6655-2021-20-3-46-53.

24. Streltsova NN, Vasiliev AP. Functional state of skin microvascular bed according to laser doppler flowmetry in patients with arterial hypertension combined with hypercholesterolemia. Regional hemodynamics and microcirculation. 2022;21(4):16-24. (In Russ.). Doi: 10.24884/1682-6655-2022-21-4-16-24.

25. Omelyanenko KV, Gorshkov AYu, Fedorovich AA, Korolev AI, Dadaeva VA, Akasheva DU, Drapkina OM. Sex features of cutaneous microvasculature in healthy working-age people. Cardiovasc Ther Prevent. 2021;20(8):48-55. (In Russ.). Doi: 10.15829/1728-8800-2021-3111.

26. Zmerenetsky KV, Kap lieva OV, Sirotina ZV, Eserskii RF. The place of microcirculation in the development of vascular disorders in children and adolescents. Far Eastern Med J. 2012;(2):59-62. (In Russ.).