Neuroscience and Behavioral Physiology

, Volume 47, Issue 1, pp 25–32 | Cite as

Mimicking the Phenomenon of Ischemic Preconditioning by Actions on Cannabinoid Receptors: The Roles of Protein Kinase C and NO Synthase

  • Yu. B. Lishmanov
  • L. N. Maslov
  • A. V. Krylatov
  • I. G. Khaliulin

Stimulation of CB1 receptors was found to mimic the phenomenon of preconditioning. As the cardioprotective effect of the cannabinoid HU-210 is seen in both in vivo experiments and in vitro studies, there are grounds for suggesting that the protective effects of HU-210 are mediated by activation of cardiac CB1 receptors. The cardioprotective effect of the cannabinoid HU-210 was found to be linked with stimulation of protein kinase C, while NO synthase has no role in the protective action of stimulation of CB1 receptors.


heart ischemia reperfusion preconditioning cannabinoids protein kinase C NO synthase 


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  1. 1.
    A. V. Krylatov, N. A. Bernatskaya, L. N. Maslov, et al., “Increases in the resistance of the heart to arrhythmic actions and decreases in the ischemic necrosis zone of the myocardium on activation of cannabinoid receptors,” Ros. Fiziol. Zh., 88, No. 5, 560–567 (2002).Google Scholar
  2. 2.
    A. V. Krylatov, L. M. Maslov, O. V. Lasukova, and R. J. Pertwee, “Cannabinoid receptor antagonists SR1417161 and SR144528 have the properties of partial agonists in experiments on isolated perfused rat hearts,” Byull. Eksperim. Biol. Med., 139, No. 5, 512–516 (2005).Google Scholar
  3. 3.
    O. V. Lasukova, L. N. Maslov, S. Yu. Ermakov, et al., “The role of cannabinoid receptors in regulating the tolerance of the heart to the effects of ischemia and reperfusion,” Izv. Ros. Akad. Nauk. Ser. Biol., 35, No. 4, 471–478 (2008).Google Scholar
  4. 4.
    Yu. B. Lishmanov, L. N. Maslov, T. Krig, and I. G. Khaliulin, “The problem of the end effector of late ischemic preconditioning of the heart,” Ros. Fiziol. Zh., 96, No. 4, 337–352 (2010).Google Scholar
  5. 5.
    V. A. Markov, V. V. Ryabov, I. V. Maksimov, et al., “Yesterday, today, and tomorrow in the diagnosis and treatment of acute myocardial infarct,” Sib. Med. Zh. (Tomsk), 26, No. 2, Iss. 1, 8–14 (2011).Google Scholar
  6. 6.
    L. N. Maslov, “New approaches to the prophylaxis and treatment of ischemic and reperfusion injury to the heart in acute myocardial infarction,” Sib. Med. Zh. (Tomsk), 25, No. 2, Iss. 1, 17–24 (2010).Google Scholar
  7. 7.
    L. N. Maslov, Yu. B. Lishmanov, and N. V. Solenkova, “Adaptation of the myocardium to ischemia. The first phase of ischemic preconditioning,” Usp. Fiziol. Nauk., 37, No. 3, 25–41 (2006).PubMedGoogle Scholar
  8. 8.
    V. V. Ryabov, E. O. Oyunarov, and V. A. Markov, “Treatment of acute myocardial infarct complicated by recurrent myocardial ischemia: comparison of the efficacies of two strategies – invasive and conservative combined with external counterpulsation,” Sib. Med. Zh. (Tomsk), 26, No. 2, Iss. 1, 42–47 (2011).Google Scholar
  9. 9.
    S. Yu. Tsibul’nikov, “Studies of the receptor nature of the opioid component of the cardioprotective effect of adaptation to chronic normobaric hypoxia,” Patogenez, No. 3, 69 (2011).Google Scholar
  10. 10.
    E. I. Chazov, “How to decrease mortality from cardiovascular diseases,” Terapev. Arkh., 80, No. 8, 11–16 (2008).Google Scholar
  11. 11.
    E. Andelova, M. Bartekova, and D. Pancza, “The role of NO in ischemia/reperfusion injury in isolated rat heart,” Gen. Physiol. Biophys., 24, No. 4, 411–426 (2005).PubMedGoogle Scholar
  12. 12.
    E. Bugge and K. Ytrehus, “Ischaemic preconditioning is protein kinase C dependent but not through stimulation of alpha adrenergic or adenosine receptors in the isolated rat heart,” Cardiovasc. Res., 29, No. 3, 401–406 (1995).PubMedGoogle Scholar
  13. 13.
    D. R. Compton, M. D. Aceto, J. Lowe, and B. R. Martin, “In vivo characterization of a specific cannabinoid receptor antagonist (SR141716A): inhibition of delta 9-tetrahydrocannabinol-induced responses and apparent agonist activity,” J. Pharmacol. Exp. Ther., 277, No. 2, 586–594 (1996).PubMedGoogle Scholar
  14. 14.
    C. DiFilippo, F. Rossi, S. Rossi, and M. D’Amico, “Cannabinoid CB2 receptor activation reduces mouse myocardial ischemia-reperfusion injury: involvement of cytokine/chemokines and PMN,” J. Leukoc. Biol., 75, No. 3, 453–459 (2004).CrossRefGoogle Scholar
  15. 15.
    Z. Ebrahim, D. M. Yellon, and G. F. Baxter, “Bradykinin elicits ‘second window’ myocardial protection in rat heart through an NOdependent mechanism,” Am. J. Physiol. Heart Circ. Physiol., 281, No. 3, H1458–H1464 (2001).PubMedGoogle Scholar
  16. 16.
    L. Facci, R. Dal Toso, S. Romanello, et al., “Mast cells express a peripheral cannabinoid receptor with different sensitivity to anandamide and palmitoylethanolamide,” Proc. Natl. Acad. Sci. USA, 92, No. 8, 33,763–33,880 (1995).CrossRefGoogle Scholar
  17. 17.
    R. M. Fryer, J. E. J. Schulz, A. K. Hsu, and G. J. Gross, “Importance of PKC and tyrosine kinase in single or multiple cycles of preconditioning in rat hearts,” Am. J. Physiol., 276, No. 4, Pt. 2, H1229–H1235 (1999).Google Scholar
  18. 18.
    L. Hanus, A. Breuer, S. Tchilibon, et al., “HU-308: a specific agonist for CB2, a peripheral cannabinoid receptor,” Proc. Natl. Acad. Sci. USA, 96, No. 25, 14228–14233 (1999).CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    P. Lepicier, J. F. Bouchard, C. Lagneux, and D. Lamontagne, “Endocannabinoids protect the rat isolated heart against ischaemia,” Br. J. Pharmacol., 139, No. 4, 805–815 (2003).CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    P. Lepicier, C. Lagneux, M. G. Sirois, and D. Lamontagne, “Endothelial CB1-receptors limit infarct size through NO formation in rat isolated hearts,” Life Sci., 81, No. 17-18, 1373–1380 (2007).CrossRefPubMedGoogle Scholar
  21. 21.
    A. H. Lichtman, J. L. Wiley, K. L. LaVecchia, et al., “Effects of SR 141716A after acute or chronic cannabinoid administration in dogs,” Eur. J. Pharmacol., 357, No. 2–3, 139–148 (1998).CrossRefPubMedGoogle Scholar
  22. 22.
    H. R. Lu, P. Yang, P. Remeysen, et al., “Ischemia/reperfusion-induced arrhythmias in anaesthetized rats: a role of Na+ and Ca2+ influx,” Eur. J. Pharmacol., 365, No. 2–3, 233–239 (1999).CrossRefPubMedGoogle Scholar
  23. 23.
    M. G. Marina Prendes, M. González, E. A. Savino, and A. Varela, “Role of endogenous nitric oxide in classic preconditioning in rat hearts,” Regul. Pept., 139, No. 1–3, 141–145 (2007).CrossRefPubMedGoogle Scholar
  24. 24.
    C. E. Murry, R. B. Jennings, and K. A. Reimer, “Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium,” Circulation, 74, No. 5, 1124–1136 (1986).CrossRefPubMedGoogle Scholar
  25. 25.
    R. G. Pertwee, “Pharmacology of cannabinoid receptor ligands,” Curr. Med. Chem., 6, No. 8, 635–664 (1999).PubMedGoogle Scholar
  26. 26.
    E. Ryberg, N. Larsson, S. Sjögren, et al., “The orphan receptor GPR55 is a novel cannabinoid receptor,” Br. J. Pharmacol., 152, No. 7, 1092–1101 (2007).CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    J. E. Schultz, Z. Yao, I. Cavero, and G. J. Gross, “Glibenclamide induced blockade of ischemic preconditioning is time dependent in intact rat heart,” Am. J. Physiol., 272, No. 6, Pt. 2, H2607–H2715 (1997).Google Scholar
  28. 28.
    Y. A. Shmist, I. Goncharov, M. Eichler, et al., “Delta-9-tetrahydrocannabinol protects cardiac cells from hypoxia via CB2 receptor activation and nitric oxide production,” Mol. Cell Biochem., 283, No. 1–2, 75–83 (2006).CrossRefPubMedGoogle Scholar
  29. 29.
    N. U. Hunderdown, C. R. Riley, and W. R. Ford, “Anandamide reduces infarct size in rat isolated hearts subjected to ischaemia-reperfusion by a novel cannabinoid mechanism,” Br. J. Pharmacol., 146, No. 6, 809–816 (2005).CrossRefGoogle Scholar
  30. 30.
    S. P. Welch, “Blockade of cannabinoid-induced antinociception by norbinaltorphimine, but not N,N-Diallyl-Tyrosine-Aib-Phenylala nine-Leucine, ICI 174,864 or naloxone in mice,” J. Pharmacol. Exp. Ther., 265, No. 2, 633–640 (1993).PubMedGoogle Scholar
  31. 31.
    D. M. Yellon and J. M. Downey, “Preconditioning the myocardium: from cellular physiology to clinical cardiology,” Physiol. Rev., 83, No. 4, 1113–1151 (2003).CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Yu. B. Lishmanov
    • 1
  • L. N. Maslov
    • 1
  • A. V. Krylatov
    • 1
  • I. G. Khaliulin
    • 2
  1. 1.Research Institute of CardiologyTomskRussia
  2. 2.University of BristolBristolUK

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