The influence of MK-801, glutamate and glycine via the modulation of N-methyl-D-aspartate receptors on isolated rat heart

Abstract

N-methyl-D-aspartate (NMDA) receptors belong to the group of inotropic glutamate receptors, which are found in rat cardiomyocytes.Aim. To evaluate the influence of a non-competitive antagonist of NMDA-receptors — МК-801, separately or in combination with glutamate and/or glycine, on cardiodynamic parameters, coronary flow and oxidative stress biomarkers in isolated rat heart.Materials and methods. 40 Wistar albino rats were divided into 4 groups (10 rats per group). Aorta of isolated rat heart was cannulated and perfused retrogradely by Krebs-Henseleit buffer in the Langendorf mode. Group 1 received МК-801 (50 µmol/l), group 2 received МК-801 and glycine (100 µmol/l), group 3 received МК-801 and glutamate (100 µmol/l) and group 4 received МК-801, glutamate and glycine. Parameters of cardiac dynamics and coronary blood flow were registered during the last minute of tested substance infusion (E) and at the point when artery perfusate samples were taken at the end of the control period (C). The difference between two points (C and E) was calculated and expressed in percent with a standard deviation.Results. Group 1 demonstrated the most prominent decrease of peak left ventricle (LV) pressure increase velocity (–47.59 ± 5.65)%, systolic and diastolic LV pressure: (–45.18 ± 4.87)% and (–37.24 ± 5.15)%, respectively and cardiac rate: (–28.63 ± 3.00)%. The most significant decrease of minimal LV pressure increase velocity was observed in group 2: (–47.43 ± 5.68)%, decrease of coronary blood flow — in group 3: (–23.02 ± 2.49)%. The most significant decline of oxidative stress biomarkers — nitrite and hydrogen peroxide — was observed in group 3: (–29.24 ± 2,70)% and (–23.43 ± 3.15)%, respectively; of superoxide anion radical (O2–) — in group 2: (–55.72 ± 6.90)%, of lipid peroxidation index — in group 1: (–35.77 ± 4.49)%.Conclusion. Administration of МК-801 results in a statistically significant decrease of cardiac dynamic parameters and lipid peroxidation index, compared to MK-801 in combination with glutamate and/or glycine.