Skip to main content
Log in

Protective effect of melatonin against myocardial injury induced by epinephrine

  • Original Paper
  • Published:
Journal of Physiology and Biochemistry Aims and scope Submit manuscript

Abstract

Epinephrine, in high doses, exhibits cardiotoxicity that is associated with excessive production of free radicals. Melatonin is antioxidant and free radical scavenger with cardioprotective properties. In our study, cardioprotective effects of melatonin against epinephrine cardiotoxicity were explored in the model of isolated rat heart. In the melatonin group, melatonin (50 μmol/l) was present in the perfusion solution during the whole experiment. In the control group, perfusion solution contained no melatonin. In both of the groups, after 30 min of initial perfusion, epinephrine was applied during 2 min directly into the heart and led to its strong stimulation. Changes in the heart function and arrhythmogenesis were evaluated before application of epinephrine and after the decline of its acute effects. No significant differences were observed during the initial perfusion. However, in the 15th and 20th minute after epinephrine application, indexes of ventricular contraction and relaxation were significantly higher in the melatonin group. Likewise, the values of the left ventricular developed pressure were significantly increased in this group in the 15th minute. These differences indicate better preservation of contraction and relaxation in the melatonin-treated group. Parameters of arrhythmogenesis—arrhythmia score, incidence and total duration of severe ventricular arrhythmias, were not significantly different between the experimental groups. However, their markedly lower average values in the melatonin-treated group suggest the reduction of electrical instability by melatonin. In conclusion, the obtained data confirm cardioprotective properties of melatonin and fill in the mosaic of information that can lead to the usage of melatonin as a therapeutic tool.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Abete P, Bianco S, Calabrese C, Napoli C, Cacciatore F, Ferrara N, Rengo F (1997) Effects of melatonin in isolated rat papillary muscle. FEBS Lett 412:79–85

    Article  CAS  PubMed  Google Scholar 

  2. Acikel M, Buyukokuroglu ME, Aksoy H, Erdogan F, Erol MK (2003) Protective effects of melatonin against myocardial injury induced by isoproterenol in rats. J Pineal Res 35:75–79

    Article  CAS  PubMed  Google Scholar 

  3. Andelová E, Barteková M, Pancza D, Styk J, Ravingerová T (2005) The role of NO in ischemia/reperfusion injury in isolated rat heart. Gen Physiol Biophys 24:411–426

    PubMed  Google Scholar 

  4. Arvola L, Bertelsen E, Lochner A, Ytrehus K (2006) Sustained anti-beta-adrenergic effect of melatonin in guinea pig heart papillary muscle. Scand Cardiovasc J 40:37–42

    Article  CAS  PubMed  Google Scholar 

  5. Bloom S, Davis DL (1972) Calcium as mediator of isoproterenol-induced myocardial necrosis. Am J Pathol 69:459–470

    PubMed Central  CAS  PubMed  Google Scholar 

  6. Buijs RM, van Eden CG, Goncharuk VD, Kalsbeek A (2003) The biological clock tunes the organs of the body: timing by hormones and the autonomic nervous system. J Endocrinol 177:17–26

    Article  CAS  PubMed  Google Scholar 

  7. Dobsak P, Siegelova J, Eicher JC, Jancik J, Svacinova H, Vasku J, Kuchtickova S, Horky M, Wolf JE (2003) Melatonin protects against ischemia-reperfusion injury and inhibits apoptosis in isolated working rat heart. Pathophysiology 9:179–187

    Article  CAS  PubMed  Google Scholar 

  8. Dominguez-Rodriguez A, Abreu-Gonzalez P, Avanzas P (2012) The role of melatonin in acute myocardial infarction. Front Biosci (Landmark Ed) 17:2433–2441

    Article  Google Scholar 

  9. Dominguez-Rodriguez A, Abreu-Gonzalez P, Sanchez-Sanchez JJ, Kaski JC, Reiter RJ (2010) Melatonin and circadian biology in human cardiovascular disease. J Pineal Res 49:14–22

    CAS  PubMed  Google Scholar 

  10. Genade S, Genis A, Ytrehus K, Huisamen B, Lochner A (2008) Melatonin receptor-mediated protection against myocardial ischaemia/reperfusion injury: role of its anti-adrenergic actions. J Pineal Res 45:449–458

    Article  CAS  PubMed  Google Scholar 

  11. Kaneko S, Okumura K, Numaguchi Y, Matsui H, Murase K, Mokuno S, Morishima I, Hira K, Toki Y, Ito T et al (2000) Melatonin scavenges hydroxyl radical and protects isolated rat hearts from ischemic reperfusion injury. Life Sci 67:101–112

    Article  CAS  PubMed  Google Scholar 

  12. Lochner A, Huisamen B, Nduhirabandi F (2013) Cardioprotective effect of melatonin against ischaemia/reperfusion damage. Front Biosci (Elite Ed) 5:305–315

    Article  Google Scholar 

  13. Mukherjee D, Roy SG, Bandyopadhyay A, Chattopadhyay A, Basu A, Mitra E, Ghosh AK, Reiter RJ, Bandyopadhyay D (2010) Melatonin protects against isoproterenol-induced myocardial injury in the rat: antioxidative mechanisms. J Pineal Res 48:251–262

    Article  CAS  PubMed  Google Scholar 

  14. Navarro-Sobrino M, Lorita J, Soley M, Ramírez I (2010) Catecholamine-induced heart injury in mice: differential effects of isoproterenol and phenylephrine. Histol Histopathol 25:589–597

    CAS  PubMed  Google Scholar 

  15. Patel V, Upaganlawar A, Zalawadia R, Balaraman R (2010) Cardioprotective effect of melatonin against isoproterenol induced myocardial infarction in rats: a biochemical, electrocardiographic and histoarchitectural evaluation. Eur J Pharmacol 644:160–168

    Article  CAS  PubMed  Google Scholar 

  16. Paulis L, Pechanova O, Zicha J, Barta A, Gardlik R, Celec P, Kunes J, Simko F (2010) Melatonin interactions with blood pressure and vascular function during L-NAME-induced hypertension. J Pineal Res 48:102–108

    Article  CAS  PubMed  Google Scholar 

  17. Paur H, Wright PT, Sikkel MB, Tranter MH, Mansfield C, O'Gara P, Stuckey DJ, Nikolaev VO, Diakonov I, Pannell L et al (2012) High levels of circulating epinephrine trigger apical cardiodepression in a β2-adrenergic receptor/Gi-dependent manner: a new model of Takotsubo cardiomyopathy. Circulation 126:697–706

    Article  CAS  PubMed  Google Scholar 

  18. Ravingerova T, Tribulova N, Slezak J, Curtis MJ (1995) Brief, intermediate and prolonged ischemia in the isolated crystalloid perfused rat heart: relationship between susceptibility to arrhythmias and degree of ultrastructural injury. J Mol Cell Cardiol 27:1937–1951

    Article  CAS  PubMed  Google Scholar 

  19. Ravingerová T, Tribulová N, Ziegelhöffer A (1993) The late effect of 7-oxo prostacyclin protects the rat heart against calcium paradox. Life Sci 53:1309–1316

    Article  PubMed  Google Scholar 

  20. Reiter RJ, Tan DX (2003) Melatonin: a novel protective agent against oxidative injury of the ischemic/reperfused heart. Cardiovasc Res 58:10–19

    Article  CAS  PubMed  Google Scholar 

  21. Rona G (1985) Catecholamine cardiotoxicity. J Mol Cell Cardiol 17:291–306

    Article  CAS  PubMed  Google Scholar 

  22. Sahna E, Parlakpinar H, Turkoz Y, Acet A (2005) Protective effects of melatonin on myocardial ischemia/reperfusion induced infarct size and oxidative changes. Physiol Res 54:491–495

    CAS  PubMed  Google Scholar 

  23. Scheer FA, Kalsbeek A, Buijs RM (2003) Cardiovascular control by the suprachiasmatic nucleus: neural and neuroendocrine mechanisms in human and rat. Biol Chem 384:697–709

    Article  CAS  PubMed  Google Scholar 

  24. Simko F, Paulis L (2007) Melatonin as a potential antihypertensive treatment. J Pineal Res 42:319–322

    Article  CAS  PubMed  Google Scholar 

  25. Singal PK, Beamish RE, Dhalla NS (1983) Potential oxidative pathways of catecholamines in the formation of lipid peroxides and genesis of heart disease. Adv Exp Med Biol 161:391–401

    Article  CAS  PubMed  Google Scholar 

  26. Szárszoi O, Asemu G, Vanecek J, Ost'ádal B, Kolár F (2001) Effects of melatonin on ischemia and reperfusion injury of the rat heart. Cardiovasc Drugs Ther 15:251–257

    Article  PubMed  Google Scholar 

  27. Tan DX, Manchester LC, Reiter RJ, Qi W, Kim SJ, El-Sokkary GH (1998) Ischemia/reperfusion-induced arrhythmias in the isolated rat heart: prevention by melatonin. J Pineal Res 25:184–191

    Article  CAS  PubMed  Google Scholar 

  28. Tengattini S, Reiter RJ, Tan DX, Terron MP, Rodella LF, Rezzani R (2008) Cardiovascular diseases: protective effects of melatonin. J Pineal Res 44:16–25

    CAS  PubMed  Google Scholar 

  29. Vazan R, Janega P, Hojná S, Zicha J, Simko F, Pechánová O, Styk J, Paulis L (2007) The effect of continuous light exposure of rats on cardiac response to ischemia-reperfusion and NO-synthase activity. Physiol Res 56(Suppl 2):S63–S69

    CAS  PubMed  Google Scholar 

  30. Walker MJ, Curtis MJ, Hearse DJ, Campbell RW, Janse MJ, Yellon DM, Cobbe SM, Coker SJ, Harness JB, Harron DW (1988) The Lambeth Conventions: guidelines for the study of arrhythmias in ischaemia infarction, and reperfusion. Cardiovasc Res 22:447–455

    Article  CAS  PubMed  Google Scholar 

  31. Zeman M, Herichova I (2013) Melatonin and clock genes expression in the cardiovascular system. Front Biosci (Schol Ed) 5:743–753

    Article  Google Scholar 

Download references

Acknowledgments

This study was supported by grants VEGA SR 2/0201/12 and APVV-0102-11. The authors are grateful to Dipl. Ing. D. Pancza for his excellent technical assistance.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Rastislav Vazan.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Vazan, R., Ravingerova, T. Protective effect of melatonin against myocardial injury induced by epinephrine. J Physiol Biochem 71, 43–49 (2015). https://doi.org/10.1007/s13105-014-0377-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13105-014-0377-5

Keywords

Navigation