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

Abstract

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.