The Effects of N-Methyl-D-Aspartate Receptor Blockade on Oxidative Status in Heart During Conditioning Maneuvers

Abstract

N-methyl-D-aspartate receptor (NMDAR) belongs to iono-tropic glutamate receptor family. The most prominent roles of the NMDAR are related to the physiological and pathophysiological processes of the central nervous system (CNS). The link between NMDAR and cardiovascular pathology came into focus due to detrimental effects of homocysteine on the cardiovascular system. Regarding the fact that NMDAR affects Ca2+ homeostasis in cells, one of the main mechanisms which mediate adverse effects of glutamate dyshomeostasis and abnormal NMDAR activity is oxidative stress. Both in ischemia and during reperfusion, there are imbalance in Ca2+ and production of reactive species, which remains one of the basic mechanisms underlining the overall cardiomyocyte death due to myocardial infarction. The aim of this study was to assess the effects of blockade of NMDAR in heart using MK-801, in preconditioning and postconditioning fashion and to compare the values of oxidative stress biomarkers. We used Langendorff technique of isolated heart. In the control group, all isolated rat hearts were subjected to global ischemia after stabilization period (perfusion of the whole heart with Krebs-Henseleit solution was stopped) for 20 minutes, followed by 30 minutes of reperfusion. In the preconditioning group, after stabilization period, hearts were perfused with MK-801 for 5 minutes, before global ischemia of 20 minutes which was followed by 30 minutes reperfusion. In the postconditioning group, hearts were perfused with MK-801 during the first 3 minutes of reperfusion. Results of this study showed antioxidative effects of NMDAR inhibition in pre- and postconditioning of the isolated rat heart.

The Role of Cardiac N-Methyl-D-Aspartate Receptors in Heart Conditioning—Effects on Heart Function and Oxidative Stress

“…Another part of the experimental protocol was dedicated to the assessment of the role of NMDAR activity in the production of oxidative species and oxidative stress. The preliminary results regarding the effects of MK-801 on oxidative stress biomarkers have been partially published [30]. One of the major mechanisms mediating in the deleterious effects of ischemia and reperfusion is oxidative stress.…”

“…TBARS-index of lipid peroxidation measured as TBARS; H 2 O 2 -hydrogen peroxide; TG-(RS)-(Tetrazol-5-yl)glycine; preC-preconditioning; postC-postconditioning. Some results regarding the effects of MK-801 on oxidative balance have been partially published[30] as a preliminary report. Statistical significance between points of interest was presented as: a-in control group; b-in glutamate group; c-in TG group; d-in memantine group; e-in MK-801 group.…”

Sex-related differences in plasma amino acids of patients with ST-elevation myocardial infarction and glycine as risk marker of acute heart failure with preserved ejection fraction

“…It has been demonstrated that NMDA activation is associated with increased intracellular calcium, impairment of nitric oxide synthesis, and increased production of reactive oxygen species, and is the one of the key causes in pathogenesis of heart failure (Kang et al 2009;Seminotti et al 2011;Martins-Pinge et al 2013;Stern and Potapenko 2013;Moura et al 2014). The role of NMDA activation in the pathogenesis of ischemic/reperfusion injury has been confirmed by the cytoprotective effect of the NMDA inhibition, especially, in pre-and postconditioning of the isolated rat heart (Weinberg et al 2016;Govoruskina et al 2019).…”