The effects of glycine, glutamate and their combination on cardiodynamics, coronary flow and oxidative stress in isolated rat hearts

Abstract

ObJeCTIVeS: To examine the effects of glycine, glutamate and their combination on cardiac function, coronary flow and oxidative stress in isolated rat hearts, and to examine the effects of potential activation of N-methyl-Daspartate (NMDA) receptors in isolated rat hearts. MeThODS: The hearts of male Wistar albino rats were excised and perfused according to the Langendorff technique, and cardiodynamic parameters (maximum rate of pressure development in the left ventricle [dp/dt max]; minimum rate of pressure development in the left ventricle [dp/dt min], systolic left ventricular pressure, diastolic left ventricular pressure, heart rate) and coronary flow were determined during the subsequent administration of glycine, glutamate and their combination. Oxidative stress biomarkers, including thiobarbituric acid-reactive substances, nitrites (NO 2 −), superoxide anion radical (O 2 −) and hydrogen peroxide (H 2 O 2), were each determined spectrophotometrically in coronary venous effluent. ReSulTS: Treatment with glycine and glutamate alone did not cause a statistically significant change in any of the observed parameters; however, their combined administration induced significant decreases in dp/dt max, dp/dt min, heart rate and coronary flow compared with the control conditions. Treatment with glycine and glutamate together induced significant increases in NO 2 − , O 2 − and H 2 O 2 levels. After the washout period, all parameters that had changed (cardiodynamic parameters, coronary flow and levels oxidative stress biomarkers) returned to values that were not significantly different from controls. CONCluSIONS: The results of the present study indicate that NMDA receptors likely have important roles in the function of the heart and coronary circulation. In addition, these results are suggestive of a damaging effect of NMDA receptor overstimulation in heart functioning, potentially mediated by oxidative stress.

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

“…Similar to previously published results, SLVP and DLVP did not change during glutamate administration [ 31 ], while the activation of NMDARs by TG induced pressor response. Most studies dealing with the effects of NMDAR and blood pressure are related to the modulation of central NMDARs and consequent pressor response [ 43 ].…”

“…Some future research on assessing the place of cardiac NMDARs in heart homeostasis should be directed to clarifying their role in the orchestration of different signaling pathways in I/R. Similar to previously published results, SLVP and DLVP did not change during glutamate administration [31], while the activation of NMDARs by TG induced pressor response. Most studies dealing with the effects of NMDAR and blood pressure are related to the modulation of central NMDARs and consequent pressor response [43].…”

“…In our previous experiments, the acute application of glutamate or NMDA alone did not change parameters of cardiodynamic parameters, while the combined application of glutamate and glycine altered cardiac contractility [22,24,31]. These variations in heart contractility could be related to the different sensitivity of heart NMDARs to glutamate and glycine, as well as the experimental technique, given that Langendorff retrograde perfusion of isolated heart implies an ex vivo technique, where substances not found in KHS are gradually washed out of the cardiac tissue.…”

Possible Role of N-Methyl-D-Aspartate Receptors in Physiology and Pathophysiology of Cardiovascular System

“…Results of experiments conducted by our research group also indicated the role of NMDA receptors in regulation of heart function. Application of glutamate or glicine did not induce any change in heart function, coronary flow or oxidative stress in retrogradely perfused rat hearts according to Langendorff technique, while on the other hand their combined use caused decrease in observed cardiodynamic parameters, coronary flow and increase in oxidative stress biomarkers (64). In the case of the combined use of glutamate and/or glycine with verapamil (blocker of L type Ca 2+ channels) in the same experimental model, the slightest changes were observed in the group where verapamil was administered along with glutamate and glycine, which suggests that the activation of the NMDA receptors allows the influx of certain amounts of Ca 2+ , insufficient to nullifies the effects of verapamil, but sufficient enough to significantly increase observed cardiodynamic parameters compared to other experimental groups in this study (65).…”