Effect of αα2-adrenoceptor stimulation on the isolated rat heart after acute myocardial infarction

Cover Page

Cite item

Full Text

Abstract

Background: α2-Adrenoceptors (α2-ARs) are a family of G protein–coupled receptors. They are located on presynaptic membranes of adrenergic fibers, postsynaptic membranes of cardiomyocytes and vascular smooth muscle cells, as well as in the peripheral and central nervous systems, intestinal and renal epithelium, and the sarcolemma of cardiomyocytes. The cardioprotective properties of myocardial α2-ARs have been demonstrated. However, the specific contribution of α2-ARs to myocardial responses after infarction remains insufficiently understood.

AIM: The work aimed to investigate the effect of α2-AR stimulation on functional parameters of the isolated rat heart in a model of acute myocardial infarction.

METHODS: The experiment involved 48 outbred rats aged 100–120 days with a mean body weight of 200–250 g. Myocardial infarction was induced by ligation of the left anterior descending coronary artery. Ex vivo experiments were performed on isolated hearts. To evaluate the effects of α2-AR stimulation, clonidine hydrochloride was administered at concentrations of 10–9 M and 10–6 M.

RESULTS: Activation of α2-ARs (10–9 M, 10–6 M) produced opposite effects on the functional parameters of the isolated heart: it increased left ventricular developed pressure and coronary flow in sham-operated rats and those with acute myocardial infarction, whereas it decreased these parameters in healthy animals. Heart rate decreased in all groups during α2-AR stimulation, whereas in healthy rats the α2-AR agonist (10–6 M) induced bidirectional changes. Stimulation of α2-ARs (10–9 M) reduced contraction duration and increased relaxation and total contraction cycle duration of the left ventricular myocardium in healthy and sham-operated rats, whereas bidirectional effects were observed in rats with acute myocardial infarction. Activation of α2-ARs (10–6 M) induced bidirectional changes in contraction, relaxation, and contraction cycle duration of the left ventricular myocardium in healthy rats. Clonidine hydrochloride (10–6 M) did not affect contraction duration but increased relaxation and total contraction cycle duration in sham-operated rats and in those with acute myocardial infarction.

CONCLUSION: Activation of α2-ARs in rats with acute myocardial infarction alters the parameters of left ventricular developed pressure and coronary flow, decreases heart rate, and exerts bidirectional effects on the time–velocity characteristics of the left ventricular myocardium.

About the authors

Anna M. Kuptsova

Kazan (Volga Region) Federal University

Author for correspondence.
Email: anuta0285@mail.ru
ORCID iD: 0000-0002-3592-6589
SPIN-code: 3695-6970

Cand. Sci. (Biology), Assistant Professor

Russian Federation, Kazan

Nafisa I. Ziyatdinova

Kazan (Volga Region) Federal University

Email: nafisaz@mail.ru
ORCID iD: 0000-0002-4503-7451
SPIN-code: 6539-5350

Dr. Sci. (Biology), Professor

Russian Federation, Kazan

Aiziriak M. Sadykov

Kazan (Volga Region) Federal University

Email: samow1995@mail.ru
ORCID iD: 0009-0009-8302-3833
SPIN-code: 2136-1107
Russian Federation, Kazan

Timur L. Zefirov

Kazan (Volga Region) Federal University

Email: zefirovtl@mail.ru
ORCID iD: 0000-0001-9557-1639
SPIN-code: 5267-1350

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Kazan

References

  1. Brodde OE, Bruck H, Leineweber K, et al. Presence, distribution and physiological function of adrenergic and muscarinic receptor subtypes in the human heart. Basic Res Cardiol. 2001;96:528–538. doi: 10.1007/s003950170003 EDN: LJXFCM
  2. Kokoz YM, Evdokimovskii EV, Maltsev AV. Upregulation of α2-adrenoceptor synthesis in SHR cardiomyocytes: Recompense without sense — Increased amounts, impaired commands. Arch Biochem Biophys. 2019;674:108109. doi: 10.1016/j.abb.2019.108109 EDN: ABCIEM
  3. Schlicker E, FeuersteinT. Human presynaptic receptors. Pharmacol. Ther. 2017;172:1–21. doi: 10.1016/j.pharmthera.2016.11.005
  4. Kaye AD, Chernobylsky DJ, Thakur P, et al. Dexmedetomidine in Enhanced Recovery After Surgery (ERAS) Protocols for Postoperative Pain. Curr Pain Headache Rep. 2020;24:21. doi: 10.1007/s11916-020-00853-z EDN: JFGQSV
  5. Bilotta F, Pugliese F. The evolving clinical use of dexmedetomidine. Lancet. 2020;396(10245):145–147. doi: 10.1016/s0140-6736(20)30902-8
  6. Gilsbach R, Hein L. Are the pharmacology and physiology of α2-adrenoceptors determined by α2-heteroreceptors and autoreceptors respectively? Br J Pharmacol. 2011;165(1):90–102. doi: 10.1111/j.1476-5381.2011.01533.x
  7. Gilsbach R, Schneider J, Lother A, et al. Sympathetic alpha2-adrenoceptors prevent cardiac hypertrophy and fibrosis in mice at baseline but not after chronic pressure overload. Cardiovasc Res. 2010;86(3):432–442. doi: 10.1093/cvr/cvq014 EDN: NZPRLX
  8. Ziyatdinova NI, Kuptsova AM, Faskhutdinov LI, et al. Effect of α2-Adrenoceptor Stimulation on Functional Parameters of Langendorff-Isolated Rat Heart. Bulletin of Experimental Biology and Medicine. 2018;165(5):593–596. doi: 10.1007/s10517-018-4220-9 EDN: MAUZED
  9. Zefirov TL, Ziatdinova NI, Khisamieva LI, Zefirov AL. Comparative Analysis of the Impact of α1- and α2-Adrenoreceptor Blockade on Cardiac Function in Rats during Postnatal Ontogeny. Bulletin of Experimental Biology and Medicine. 2011;151(6):664–666. doi: 10.1007/s10517-011-1410-0 EDN: PEELUZ
  10. Korotaeva YuV, Tsirkin VI. Alpha2-adrenergic receptors of myocardium (Review). Proceedings of THE Komi Science centre of the Ural division of the Russian Academy of Sciences. 2015;2(22):57–64. EDN: TXJHMT
  11. Zefirov TL, Ziyatdinova NI, Khisamieva LI, Zefirov AL. Effect of α2-Adrenoceptor Stimulation on Cardiac Activity in Rats. Bulletin of Experimental Biology and Medicine. 2014;157(2):194–197. doi: 10.1007/s10517-014-2523-z EDN: UEJENT
  12. Kuptsova AM, Zaripova RI, Hisamieva LI, et al. Yohimbine influence on myocardium contractile activity among newborn rats. International Journal of Advanced Biotechnology and Research. 2016;7(4):1305–1309.
  13. Nahrendorf M, Wiesmann F, Hiller KH, et al. Serial cine-magnetic resonance imaging of left ventricular remodeling after myocardial infarction in rats. J Magn Reson Imaging. 2001:14(5):547–555. doi: 10.1002/jmri.1218
  14. Pimenov OY, Galimova MH, Evdokimovskii EV, et al. Myocardial α2-Adrenoceptors as Therapeutic Targets to Prevent Cardiac Hypertrophy and Heart Failure. Biophysics. 2019;64(5):917–932. doi: 10.1134/S0006302919050120 EDN: THCLQM
  15. Cai JJ, Morgan DA, Haynes WG, et al. Alpha2-Adrenergic stimulation is protective against ischemia-reperfusion-induced ventricular arrhythmias in vivo. Am J Physiol Heart Circ Physiol. 2002;283(6):H2606–2611. doi: 10.1152/ajpheart.00156.2002
  16. Yoshikawa Y, Hirata N, Kawaguchi R, et al. Dexmedetomidine maintains its direct cardioprotective effect against ischemia/reperfusion injury in hypertensive hypertrophied myocardium. Anesthesia and Analgesia. 2018;126(2):443–452. doi: 10.1213/ANE.0000000000002452 EDN: VIAJTN
  17. Takahashi K, Yoshikawa Y, Kanda M, et al. Dexmedetomidine as a cardioprotective drug: a narrative review. Journal of Anesthesia. 2023;37:961–970. doi: 10.1007/s00540-023-03261-w EDN: ONEYNT
  18. Kuptsova AM, Bugrov RK, Khabibrakhmanov II, et al. Role of α2-adrenoceptors in Rat Heart with the Model of myocardial Infarction. J Chem Health Risks. 2021;11(2):129–134. doi: 10.22034/jchr.2021.682031 EDN: GUPDYB
  19. Mill JG, Stefanon I, Santos L, Baldo MP. Remodeling in the ischemic heart: the stepwise progression for heart failure. Brazilian Journal of Medical and Biological Research. 2011;44(9):890–898. doi: 10.1590/S0100-879X2011007500096
  20. Grin VK, Konoplyanko VA, Mikhailichenko VYu. Peculiarities of chronotropic response to the stress in rats with a model of myocardial infarction. Vestnik neotlozhnoy i vosstanovitel'noy meditsiny. 2006;7(1):102–104.
  21. Kuptsova AM, Bugrov RK, Ziyatdinova NI, Zefrov TL. Langendorff-Isolated Rat Heart after Acute Еxperimental Myocardial Infarction. Вulletin of Experimental Biology and Medicine. 2022;173(6):719–722. doi: 10.1007/s10517-022-05623-y EDN: ANEHGK
  22. Kuptsova AM, Bugrov RK, Ziyatdinova NI, Zefirov TL. Peracute Myocardial Infarction: Features of the Influence of α2-Adrenoreceptor Stimulation on the Isolated Heart. Вulletin of Experimental Biology and Medicine. 2024;176(3):315–320. doi: 10.1007/s10517-024-06015-0 EDN: HFBNXC
  23. Kozlovskiy VI. The role of endothelium in vasodilation mediated by different subtypes of adrenoceptors. Journal of the Grodno state medical university. 2010;1:32–35. EDN: QAVKED
  24. Nikulina NA, Dotsenko EA, Nerovnya AM, et al. Experimental myocardial infarction in rats: features of modeling and course within the first 48 hours after coronary artery ligation. Problems of health and ecology. 2020;2(64):91–96. doi: 10.51523/2708-6011.2020-17-2-13 EDN: YFXOSR

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig. 1. Original recordings of an experimental study of rats with an acute myocardial infarction model: a, the dynamics of left ventrical pressure α2-AR stimulation (10–6 M); b, the dynamics of coronary flow during α2-AR stimulation (10–6 M); c, the values of left ventrical pressure of an isolated heart during α2-AR stimulation (10–9 M), original recording; d, electrogram, original recording.

Download (232KB)
Indexing metadata
3. Fig. 2. The effect of α2-АR stimulation (10−9 M and 10–6 M) on left ventrical pressure (a, b), heart rate (c, d), and coronary flow (e, f) in healthy rats, sham-operated rats, and rats with acute myocardial infarction. The reliability is indicated in comparison with the initial values: * — p < 0.05, ** — p < 0.01, *** — p < 0.001 (healthy); x — p < 0.05, xx — p < 0.01 (sham-operated rats); # — p < 0.05, ## — p < 0.01 (rats with an acute myocardial infarction model).

Download (416KB)
Indexing metadata
4. Fig. 3. The effect of α2-АR stimulation (10–9 M and 10–6 M) on the contraction time (a, b), relaxation time (c, d) and the contraction cycle time of the left ventricular myocardium (e, f) in healthy rats, sham-operated rats and rats with acute myocardial infarction. The reliability is indicated in comparison with the initial values: * — p < 0.05, ** — p < 0.01 (healthy); x — p < 0.05, xx — p < 0.01 (sham-operated rats), # — p < 0.05; ## — p < 0.01 (rats with acute myocardial infarction model). ЛО — sham-operated, ИМ — myocardial infarction.

Download (432KB)
Indexing metadata

Copyright (c) 2025 Eco-Vector

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Согласие на обработку персональных данных

 

Используя сайт https://journals.rcsi.science, я (далее – «Пользователь» или «Субъект персональных данных») даю согласие на обработку персональных данных на этом сайте (текст Согласия) и на обработку персональных данных с помощью сервиса «Яндекс.Метрика» (текст Согласия).