The effects of verapamil and its combinations with glutamate and glycine on cardiodynamics, coronary flow and oxidative stress in isolated rat heart.
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.
Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.
Isidora
I
Stojic
Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.
Ivan
I
Srejovic
Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.
Vladimir
V
Zivkovic
Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.
Nevena
N
Jeremic
University Clinical Hospital Center "Dr Dragisa Misovic", University of Belgrade, Belgrade, Serbia.
Marko
M
Djuric
University Clinical Hospital Center "Dr Dragisa Misovic", University of Belgrade, Belgrade, Serbia.
Ana
A
Stevanovic
Department of Biochemistry, Faculty of Medicine, University of Prishtina/Kosovska Mitrovica, Kosovska Mitrovica, Serbia.
Tamara
T
Milanovic
Institute of Medical Physiology "Richard Burian," Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
Dragan
D
Djuric
Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia. drvladakgbg@yahoo.com.
Vladimir
V
Jakovljevic
D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000494:pharmacology*; D020013:Calcium Signaling / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism*; D005998:Glycine / Q000378:metabolism*; D006321:Heart / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists* / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology; D014700:Verapamil / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D015415:Biomarkers; D002121:Calcium Channel Blockers; D016194:Receptors, N-Methyl-D-Aspartate; D014665:Vasodilator Agents; D018698:Glutamic Acid; D014700:Verapamil; D005998:Glycine
Glutamate; Glycine; Isolated rat heart; N-methyl-D-aspartate receptor; Oxidative stress; Verapamil