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The effects of the modulation of NMDA receptors by homocysteine thiolactone and dizocilpine on cardiodynamics and oxidative stress in isolated rat heart

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Abstract

In light of the limited data concerning the role of N-methyl-D-aspartate (NMDA) receptors in cardiac function, the aim of the present study was to determine the role of NMDA receptors in cardiac function, as well as the possible role played by the oxidative stress induced by the overstimulation of NMDA receptors in isolated rat heart. The hearts of male, Wistar albino rats (n = 24, 12 in each experimental group, BM 180–200 g) were retrogradely perfused at a constant perfusion pressure (70 cm H2O), using the Langendorff technique, and cardiodynamic parameters were determined during the subsequent administration of DL-homocysteine thiolactone (DL-Hcy TLHC) alone, the combination of DL-Hcy TLHC and dizocilpine (MK-801), and MK-801 alone. In the second experimental group, the order of the administration of each of the substances was reversed. The oxidative stress biomarkers, including thiobarbituric acid reactive substances (TBARS), NO2 −, O2 − and H2O2, were each determined spectrophotometrically. DL-Hcy TLHC and MK-801 depressed cardiac function. DL-Hcy TLHC decreased oxidative stress, a finding that contrasted with the results of the experiments in which MK-801 was administered first. The findings of this study were suggestive of the likely role played by NMDA receptors in the regulation of cardiac function and coronary circulation in isolated rat heart.

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Abbreviations

NMDA:

N-methyl-D-aspartate

DL-Hcy TLHC:

DL-homocysteine thiolactone

AMPA:

α-Amino-3-hydrohy-5-methyl-4-izoxazolepropionate

NR1:

Glycine-binding subunit

NR2:

Glutamate-binding subunit

CNS:

Central nervous system

Hcy:

Homocysteine

HHcy:

Hyperhomocysteinemia

MMP-9:

Metalloproteinase-9

CF:

Coronary flow

dp/dt max:

Maximum rate of pressure development in the left ventricle

dp/dt mix:

Minimum rate of pressure development in the left ventricle

SLVP:

Systolic left ventricular pressure

DLVP:

Diastolic left ventricular pressure

HR:

Heart rate

TBARS:

Thiobarbituric acid reactive substances

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Acknowledgments

This project was supported by Grant No. 175043 from the Ministry of Science and Technical Development of the Republic of Serbia, and the Junior Project 04/2011, Faculty of Medical Sciences, University of Kragujevac, Serbia.

Conflict of interests

None of the authors of the present study has any actual or potential conflicts of interest to disclose, including financial, personal, or other relationships with specific persons or organisations.

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Authors and Affiliations

  1. Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia

    Ivan Srejovic, Vladimir Jakovljevic & Vladimir Zivkovic

  2. Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia

    Nevena Barudzic & Ana Radovanovic

  3. Institute of Medical Physiology “Richard Burian”, School of Medicine, University of Belgrade, Belgrade, Serbia

    Olivera Stanojlovic & Dragan M. Djuric

Authors
  1. Ivan Srejovic
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  2. Vladimir Jakovljevic
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  3. Vladimir Zivkovic
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  4. Nevena Barudzic
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Correspondence to Vladimir Jakovljevic.

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Srejovic, I., Jakovljevic, V., Zivkovic, V. et al. The effects of the modulation of NMDA receptors by homocysteine thiolactone and dizocilpine on cardiodynamics and oxidative stress in isolated rat heart. Mol Cell Biochem 401, 97–105 (2015). https://doi.org/10.1007/s11010-014-2296-8

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  • DOI: https://doi.org/10.1007/s11010-014-2296-8

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