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The effects of verapamil and its combinations with glutamate and glycine on cardiodynamics, coronary flow and oxidative stress in isolated rat heart

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Abstract

The role of N-methyl-D-aspartate receptor (NMDA-R) in heart is still unclear. For these ionotropic glutamate receptors is characteristic the necessity of both co-agonists, glutamate and glycine, for their activation, which primarily allows influx of calcium. The aim of the present study was to examine the effects of verapamil, as a calcium channel blocker, alone and its combination with glycine and/or glutamate on cardiac function, coronary flow, and oxidative stress in isolated rat heart or to examine the effects of potential activation of NMDA-R in isolated rat heart. The hearts of male Wistar albino rats were excised and perfused according to Langendorff technique, and cardiodynamic parameters and coronary flow were determined during the administration of verapamil and its combinations with glutamate and/or glycine. The oxidative stress biomarkers, including thiobarbituric acid-reactive substances, nitrites, superoxide anion radical, and hydrogen peroxide, were each determined spectrophotometrically from coronary venous effluent. The greatest decline in parameters of cardiac contractility and systolic pressure was in the group that was treated with verapamil only, while minimal changes were observed in group treated with all three tested substances. Also, the largest changes in coronary flow were in the group treated only with verapamil, and at least in the group that received all three tested substances, as well as the largest increase in oxidative stress parameters. Based on the obtained results, it can be concluded that NMDA-R activation allows sufficient influx of calcium to increase myocardial contractility and systolic pressure, as well as short-term increase of oxidative stress.

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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.

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Authors and Affiliations

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

    Isidora Stojic & Nevena Jeremic

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

    Ivan Srejovic, Vladimir Zivkovic & Vladimir Jakovljevic

  3. University Clinical Hospital Center “Dr Dragisa Misovic”, University of Belgrade, Belgrade, Serbia

    Marko Djuric & Ana Stevanovic

  4. Department of Biochemistry, Faculty of Medicine, University of Prishtina/Kosovska Mitrovica, Kosovska Mitrovica, Serbia

    Tamara Milanovic

  5. Institute of Medical Physiology “Richard Burian,” Faculty of Medicine, University of Belgrade, Belgrade, Serbia

    Dragan Djuric

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  1. Isidora Stojic
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  2. Ivan Srejovic
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Correspondence to Vladimir Jakovljevic.

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Stojic, I., Srejovic, I., Zivkovic, V. et al. The effects of verapamil and its combinations with glutamate and glycine on cardiodynamics, coronary flow and oxidative stress in isolated rat heart. J Physiol Biochem 73, 141–153 (2017). https://doi.org/10.1007/s13105-016-0534-0

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