Pathophysiology

doi: 10.25005/2074-0581-2023-25-1-71-83
EFFECT OF ACTH6-9-PRO-GLY-PRO PEPTIDE ON SPECTRAL PARAMETERS OF HEART RATE VARIABILITY IN WISTAR RATS DURING PHYSICAL EXERTION (PILOT STUDY)

V.N. Korobova, A.O. Vorvul, I.I. Bobyntsev

Department of Pathophysiology, Research Institute of General Pathology, Kursk State Medical University, Kursk, Russian Federation

Objective: To study the effect of the ACTH6-9-Pro-Gly-Pro peptide (ACTH6-9-PGP) on the spectral parameters of heart rate variability (HRV) in Wistar rats during short-term exercise.

Methods: The study involved 48 Wistar rats. ACTH6-9-PGP was once administered to the animals intraperitoneally at doses of 5, 50, and 500 µg/kg (3 groups of animals) in a volume of 1 ml/kg. Animals of the control group were injected with normal saline in an equivalent volume. Each group included 6 males and 6 females. HRV indicators were recorded using the Physiobelt 2.5.1 complex (Neurobotics, Russia). HRV analysis was performed by spectral parameters: total power of the spectrum of HRV (TP), the total power of the high-frequency component (HF) (ms2 , %), the total power of the lowfrequency component (LF) (ms2 , %), the total power of the very low-frequency component (VLF) (ms2 , %), LF/HF ratio (LF/HF), index of centralization (IC). The cardio signal was recorded 4 times: 1 – after adaptation to the device; 2 – 15 minutes after the injection of the peptide; 3 – after physical activity (2-minute treadmill run), and 4 – after a 15-minute rest.

Results: An analysis of the initial values of the HRV indicators made it possible to establish a shift in the spectral characteristics toward the VLF component in the studied groups. Physical activity in the control group caused an increase in the power of HF, LF, and VLF, however, their ratio (VLF>LF>HF) did not change at all stages of the study. A single intraperitoneal injection of the ACTH6-9-PGP peptide at a dose of 5 μg/kg stabilized the HRV parameters at the initial level. The administration of the peptide at a dose of 50 μg/kg and moderate physical activity were accompanied by an increase in the power of HF and LF compared to the initial level. The percentage of frequency components after the exercise was LF>VLF>HF, and in the recovery period, it became VLF>LF>HF. After the administration of the peptide at a dose of 500 μg/kg, an increase in HF and LF, and a redistribution of the frequency components toward LF>HF>VLF were noted. During the recovery period, a decrease in HF, restoration of the percentage of frequency indicators VLF>LF>HF, and an increase in LF/HF and IC were found.

Conclusion: A study of the effects of the ACTH6-9-PGP peptide on HRV in Wistar rats showed that a single intraperitoneal injection at a dose of 5 µg/kg promotes adaptation of laboratory animals to physical activity due to the activation of suprasegmental structures, and at doses of 50 and 500 µg/kg – predominant activation of the peripheral segments of the sympathetic and parasympathetic autonomic systems.

Keywords: ACTH6-9-Pro-Gly-Pro, heart rate variability, physical activity, Wistar rats, spectral parameters.

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References
  1. Koroleva SV, Myasoedov NF. Semax as a universal drug for therapy and research. Biol Bull Russ Acad Sci. 2018;45(6):589-600. https://doi.org/10.1134/ S1062359018060055
  2. Arushanyan EB, Popov AV. Vliyanie semaksa na variabel'nost' serdechnogo ritma krys v raznoe vremya sutok [Effect of semax on heart rate variability in various daytime periods]. Eksperimental'naya i klinicheskaya farmakologiya. 2009;72(2):32-4. https://doi.org/10.30906/0869-2092-2009-72-2-32-34
  3. Todorovic A, Lensing CJ, Holder JR, Scott JW, Sorensen NB, et al. Discovery of melanocortin ligands via a double simultaneous substitution strategy based on the Ac-His-DPhe-Arg-Trp-NH2 template. ACS Chem Neurosci. 2018;9(11):2753- 66. https://doi.org/10.1021/acschemneuro.8b00181
  4. Levitskaya NG, Glazova NYu, Sebentsova EA, Manchenko DM, Andreeva LA, Kamensky AA, i dr. Nootropnye i anksioliticheskie effekty geptapeptida AKTG6-9Pro-Gly-Pro [Nootropic and anxiolytic effects of heptapeptide ACTH6-9Pro-Gly-Pro]. Rossiyskiy fiziologicheskiy zhurnal imeni I.M. Sechenova. 2019;105(6):761-70. https://doi.org/10.1134/S0869813919060049
  5. Dodonova SA, Bobyntsev II, Belykh AE, Vorvul AO. ACTH6-9-PGP improves memory consolidation processes in rats. Research Results in Pharmacology. 2021:7(1):27-32. https://doi.org/10.3897/rrpharmacology.7.62479
  6. Dodonova SA, Bobyntsev II, Belykh AE, Andreeva LA, Myasoedov NF. Changes in the nociceptive response to thermal stimulation in rats following administration of N-terminal analogs of the adrenocorticotropic hormone. Bulletin of RSMU. 2019;6:33-6. https://doi.org/10.24075/brsmu.2019.085
  7. Vorvul AO, Bobyntsev II, Medvedeva OA, Mukhina AY, Svishcheva MV, Azarova IE, et al. ACTH6-9-Pro-Gly-Pro ameliorates anxiety-like and depressive-like behaviour and gut mucosal microbiota composition in rats under conditions of chronic restraint stress. Neuropeptides. 2022;93:102247. https://doi. org/10.1016/j.npep.2022.102247
  8. Cryan JF, O'Riordan KJ, Cowan CSM, Sandhu KV, Bastiaanssen TFS, Boehme M, et al. The Microbiota-gut-brain axis. Physiol Rev. 2019;99(4):1877-2013. https://doi.org/10.1152/physrev.00018.2018
  9. Baevskiy RM, Ivanov GG, Chireykin LV, Gavrilushkin AP, Dovgalevskiy PYa, Kukushkin YuA, i dr. Analiz variabel'nosti serdechnogo ritma pri ispol'zovanii razlichnykh elektrokardiograficheskikh sistem (chast' 1) [Analysis of heart rate variability using various electrocardiographic systems (Part 1)]. Vestnik aritmologii. 2002;24:65-87.
  10. Morozova MP, Lukoshkova EV, Gavrilova SA. Osobennosti otsenki variabel'nosti ritma serdtsa u krys [Some aspects of heart rate variability estimation in rats]. Rossiyskiy fiziologicheskiy zhurnal imeni I.M. Sechenova. 2015;101(3):291-307.
  11. Korobova VN, Vorvul AO, Bobyntsev II, Khabibulin RR, Kostyunin IN. Variabel'nost' serdechnogo ritma krys-samok Vistar v usloviyakh razlichnoy fizicheskoy aktivnosti [Heart rate variability in female Wistar rats under conditions of different physical activity]. Chelovek i ego zdorov'e. 2022;25(3):32-41. https:// doi.org/10.21626/vestnik/2022-3/05
  12. Kastyro IV, Khamidulin GV, Shmaevsky PE, Torshin VI, Ermakova NV, Popadyuk VI, et al. The effect of surgical trauma in the nasal cavity on the behavior in the open field and the autonomic nervous system of rats. Dokl Biochem Biophys. 2020;492(1):121-3. https://doi.org/10.1134/S1607672920030023
  13. Kuryanova EV, Tryasuchev AV, Stupin VO, Teplyi DL. Effect of atropine on adrenergic responsiveness of erythrocyte and heart rhythm variability in outbred rats with stimulation of the central neurotransmitter systems. Bull Exp Biol Med. 2018;165(5):597-601. https://doi.org/10.1007/s10517-018-4221-8
  14. Garabedian C, Champion C, Servan-Schreiber E, Butruille L, Aubry E, Sharma D, et al. A new analysis of heart rate variability in the assessment of fetal parasympathetic activity: An experimental study in a fetal sheep model. PLoS One. 2017;12(7):e0180653. https://doi.org/10.1371/journal.pone.0180653
  15. Kuryanova EV, Tryasuchev AV, Stupin VO, Zhukova YD. Peculiarities of heart rate variability changes in random-bred male rats during transition into anesthetic sleep under stimulation of central neurotransmitter systems. Bull Exp Biol Med. 2021;170(5):585-9. https://doi.org/10.1007/s10517-021-05111-9
  16. Ivanov DG, Aleksandrovskaya NV, Afonkina EA, Eroshkin PV, Semyonov AN, Busygin DV. Adaptatsionnye izmeneniya u krys pri ezhednevnom vypolnenii fizicheskoy nagruzki v metodike «Beg na tredbane» [Adaptive changes in rats under everyday physical load in "The run on treadmill" method]. Biomeditsina. 2017;2:4-22.
  17. Kuryanova EV, Tryasuchev AV, Stupin VO, Zhukova YuD, Gorst NA. Vliyanie blokady vegetativnykh gangliev, M-kholino- i β-adrenoretseptorov miokarda na variabel'nost' serdechnogo ritma krys [Influence of blockade of the vegetative ganglions, of myocardial M-cholinoreceptors and beta-adrenoreceptors on the heart rate variability in rats]. Rossiyskiy fiziologicheskiy zhurnal imeni I.M. Sechenova. 2020;106(1):17-30. https://doi.org/10.31857/S0869813920010070
  18. Kastyro IV, Torshin VI, Khamidulin GV, Inozemtsev AN, Yakshina EV, Rogovaya AV, i dr. Travmatizatsiya slizistoy obolochki peregorodki nosa krys izmenyaet povedenie i balans vegetativnoy nervnoy sistemy [Traumatisation the mucosus membrane of nasal septum change behavior and balance of the vegetative nervous system of rats]. Golova i sheya. 2022;10(S2S2):20-7. https://doi. org/10.25792/HN.2022.10.2.S2.20-27
  19. Fazeli MS, Pourrahmat MM, Liu M, Guan L, Collet JP. The effect of head massage on the regulation of the cardiac autonomic nervous system: A pilot randomized crossover trial. J Altern Complement Med. 2016;22(1):75-80. https:// doi.org/10.1089/acm.2015.0141
  20. Yang Y, Xu Y. The central melanocortin system and human obesity. J Mol Cell Biol. 2020;12(10):785-97. https://doi.org/110.1093/jmcb/mjaa048
  21. Krude H, Biebermann H, Schnabel D, Tansek MZ, Theunissen P, Mullis PE, et al. Obesity due to proopiomelanocortin deficiency: Three new cases and treatment trials with thyroid hormone and ACTH4-10. J Clin Endocrinol Metab. 2003;88(10):4633-40. https://doi.org/10.1210/jc.2003-030502
  22. Hill JW, Faulkner LD. The role of the melanocortin system in metabolic disease: New developments and advances. Neuroendocrinology. 2017;104(4):330-46. https://doi.org/10.1159/000450649
  23. Clark AJ, Forfar R, Hussain M, Jerman J, McIver E, Taylor D, et al. ACTH antagonists. Front Endocrinol (Lausanne). 2016;(7):101. https://doi.org/10.3389/ fendo.2016.00101
  24. Konda Y, Gantz I, DelValle J, Shimoto Y, Miwa H, Yamada T. Interaction of dual intracellular signaling pathways activated by the melanocortin-3 receptor. J Biol Chem. 1994;269(18):13162-6
  25. Buggy JJ. Binding of alpha-melanocyte-stimulating hormone to its G-protein-coupled receptor on B-lymphocytes activates the Jak/STAT pathway. Biochem J. 1998;331(Pt1)(Pt1):211-6. https://doi.org/10.1042/bj3310211

Authors' information:


Korobova Viktoria Nikolaevna,
Candidate of Medical Sciences, Senior Lecturer at the Department of Pathophysiology, Senior Researcher at the Research Institute of General Pathology, Kursk State Medical University
Scopus ID: 57219598765
ORCID ID: 0000-0002-2737-3435
SPIN-код: 5193-4027
Author ID: 838407
E-mail: viktoria.korobova@mail.ru

Vorvul Anton Olegovich,
Full-time Postgraduate Student, Assistant Lecturer at the Department of Pathophysiology, Junior Researcher at the Research Institute of General Pathology, Kursk State Medical University
Researcher ID: AAE-2202-2022
Scopus ID: 57222709711
ORCID ID: 0000-0002-1529-6014
SPIN-код: 8398-9376
Author ID: 1037601
E-mail: vorvul1996@mail.ru

Bobyntsev Igor Ivanovich,
Doctor of Medical Sciences, Full Professor, Head of the Department of Pathophysiology, Head of the Research Institute of General Pathology, Kursk State Medical University
Researcher ID: H-8849-2013
Scopus ID: 6602416028
ORCID ID: 0000-0001-7745-2599
SPIN-код: 3947-0114
Author ID: 276199
E-mail: bobig@mail.ru

Information about support in the form of grants, equipment, medications

The work was supported by the Kursk State Medical University (Contract No. 16 for the provision of paid services dated March 17, 2022).

Conflicts of interest: No conflict

Address for correspondence:


Korobova Viktoria Nikolaevna
Candidate of Medical Sciences, Senior Lecturer at the Department of Pathophysiology, Senior Researcher at the Research Institute of General Pathology, Kursk State Medical University

305041, Russian Federation, Kursk, K. Marx str., 3

Tel.: +7 (915) 5124066

E-mail: viktoria.korobova@mail.ru

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