Journal of Physiology and Biochemistry

, Volume 73, Issue 1, pp 141–153 | Cite as

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

  • Isidora Stojic
  • Ivan Srejovic
  • Vladimir Zivkovic
  • Nevena Jeremic
  • Marko Djuric
  • Ana Stevanovic
  • Tamara Milanovic
  • Dragan Djuric
  • Vladimir JakovljevicEmail author
Original Article


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.


Verapamil Glutamate Glycine N-methyl-D-aspartate receptor Oxidative stress Isolated rat heart 



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.

Compliance with ethical standards

Conflict of interests

The authors declare that they have no competing interests.


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Copyright information

© University of Navarra 2016

Authors and Affiliations

  • Isidora Stojic
    • 1
  • Ivan Srejovic
    • 2
  • Vladimir Zivkovic
    • 2
  • Nevena Jeremic
    • 1
  • Marko Djuric
    • 3
  • Ana Stevanovic
    • 3
  • Tamara Milanovic
    • 4
  • Dragan Djuric
    • 5
  • Vladimir Jakovljevic
    • 2
    Email author
  1. 1.Department of Pharmacy, Faculty of Medical SciencesUniversity of KragujevacKragujevacSerbia
  2. 2.Department of Physiology, Faculty of Medical SciencesUniversity of KragujevacKragujevacSerbia
  3. 3.University Clinical Hospital Center “Dr Dragisa Misovic”University of BelgradeBelgradeSerbia
  4. 4.Department of Biochemistry, Faculty of MedicineUniversity of Prishtina/Kosovska MitrovicaKosovska MitrovicaSerbia
  5. 5.Institute of Medical Physiology “Richard Burian,” Faculty of MedicineUniversity of BelgradeBelgradeSerbia

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