scholarly journals Modulation ofN-methyl-d-aspartate receptors in isolated rat heart

2017 ◽  
Vol 95 (11) ◽  
pp. 1327-1334 ◽  
Author(s):  
Ivan Srejovic ◽  
Vladimir Zivkovic ◽  
Tamara Nikolic ◽  
Nevena Jeremic ◽  
Isidora Stojic ◽  
...  

Considering the limited data on the role of NMDA-Rs in the cardiovascular system, the aim of the present study was to examine the effects of NMDA and DL-Hcy TLHC, alone and in combination with glycine, memantine, and ifenprodil, in the isolated rat heart. The hearts of Wistar albino rats were retrogradely perfused according to the Langendorff technique at a constant perfusion pressure. The experimental protocol for all experimental groups included the stabilization period, application of estimated substance for 5 min, followed by a washout period of 10 min. Using a sensor placed in the left ventricle, we registered the following parameters of myocardial function: dp/dtmax, dp/dtmin, SLVP, DVLP, HR; CF was measured using flowmetry). We estimated the following oxidative stress biomarkers in the coronary venous effluent using spectrophotometry: TBARS, NO2−, O2−, and H2O2. NMDA alone did not induce any change in any of the observed parameters, while DL-Hcy TLHC alone, as well as a combined application of NMDA and DL-Hcy TLHC with glycine, induced a reduction of most cardiodynamic parameters. Memantine and ifenprodil induced a reduction of cardiodynamic parameters and CF, as well as some oxidative stress biomarkers.

Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1065
Author(s):  
Natalia Govoruskina ◽  
Vladimir Jakovljevic ◽  
Vladimir Zivkovic ◽  
Isidora Milosavljevic ◽  
Jovana Jeremic ◽  
...  

As well as the most known role of N-methyl-D-aspartate receptors (NMDARs) in the nervous system, there is a plethora of evidence that NMDARs are also present in the cardiovascular system where they participate in various physiological processes, as well as pathological conditions. The aim of this study was to assess the effects of preconditioning and postconditioning of isolated rat heart with NMDAR agonists and antagonists on heart function and release of oxidative stress biomarkers. The hearts of male Wistar albino rats were subjected to global ischemia for 20 min, followed by 30 min of reperfusion, using the Langendorff technique, and cardiodynamic parameters were determined during the subsequent preconditioning with the NMDAR agonists glutamate (100 µmol/L) and (RS)-(Tetrazol-5-yl)glycine (5 μmol/L) and the NMDAR antagonists memantine (100 μmol/L) and MK-801 (30 μmol/L). In the postconditioning group, the hearts were perfused with the same dose of drugs during the first 3 min of reperfusion. The oxidative stress biomarkers were determined spectrophotometrically in samples of coronary venous effluent. The NMDAR antagonists, especially MK-801, applied in postconditioning had a marked antioxidative effect with a most pronounced protective effect. The results from this study suggest that NMDARs could be a potential therapeutic target in the prevention and treatment of ischemic and reperfusion injury of the heart.


2015 ◽  
Vol 16 (3) ◽  
pp. 193-199
Author(s):  
Sasa Plecevic ◽  
Olga Pechanova ◽  
Andrej Barta ◽  
Aleksandra Vranic ◽  
Jovana Jeremic ◽  
...  

AbstractIncreased activity of the renin-angiotensin-aldosterone system (RAAS) plays a significant role in the development and progression of various cardio-metabolic diseases, such as hypertension, atherosclerosis and heart failure. Aliskiren is the newest antihypertensive drug and the first orally active direct renin inhibitor to become available for clinical use. This study investigated the acute and direct effects of Aliskiren on different parameters of oxidative stress on isolated rat heart. The hearts of male Wistar albino rats (n = 24, 8 per experimental group, age 8 weeks, body mass 180–200 g), were excised and retrogradely perfused according to the Langendorfftechnique at a gradually increasing perfusion pressure (40-120 cmH2O). Markers of oxidative stress (NO2−, TBARS, H2O2 and O2−) were measured spectrophotometrically after perfusion with three different concentrations of Aliskiren (0.1 μM, 1 μM, and 10 μM). The results demonstrated possible dose-dependent cardioprotective properties of Aliskiren, particularly with higher CPP. Lipid peroxidation (TBARS) levels decreased with the highest dose of Aliskiren and higher CPP, and the same trend was observed in nitrite (NO2−) and hydrogen peroxide (H2O2) levels. These findings indicate that the acute effects of Aliskiren do not likely promote the production of reactive oxygen species upon higher pressure with the highest dose. Aliskiren may exert beneficial effects on oxidative stress biomarkers.


2017 ◽  
Vol 439 (1-2) ◽  
pp. 19-33 ◽  
Author(s):  
Isidora M. Stojic ◽  
Vladimir I. Zivkovic ◽  
Ivan M. Srejovic ◽  
Tamara R. Nikolic ◽  
Nevena S. Jeremic ◽  
...  

Author(s):  
Jelena Smigic ◽  
Isidora Stojic ◽  
Vladimir Zivkovic ◽  
Ivan Srejovic ◽  
Tamara Nikolic ◽  
...  

Abstract Taken into consideration that molecular and cellular mechanisms involved in cardiotoxicity are still not clear the aim of this study was to compare the production of oxidative stress parameters in the isolated rat heart between animals chronically treated with cisplatin and saline. Th e hearts of male Wistar albino rats (n = 24, 12 per group, age 8 weeks, body mass 250±50 g) were excised and perfused according to the Langendorff technique at gradually increased coronary perfusion pressures (40-120 cmH2O). We followed the production of superoxide anion radicals, hydrogen peroxide, and nitrites and also index of lipid peroxidation during the changes of coronary perfusion pressure (CPP) (from 40 to 120 cm H2O) in coronary venous effluent. Modifications CPP were performed in order to determined if oxidative stress is involved in coronary endothelium response in conditions of hypoxia (lower than 60 cm H2O) and hyperoxia (higher than 80 cm H2O). Based on the results of this research we can conclude that with enhancement of CPP the values of oxidative stress statistically increased. However, this increment is more prominent in control group as a result of preserved endothelium and its more powerful response to hyperoxia. On the other hand, damaged endothelium of cisplatin-treated animals had weaker response to hyperoxia, and also lower antioxidant capacity.


2016 ◽  
Vol 103 (4) ◽  
pp. 428-438 ◽  
Author(s):  
M Stojanovic ◽  
V Zivkovic ◽  
I Srejovic ◽  
V Jakovljevic ◽  
N Jeremic ◽  
...  

This study aimed to assess the role of H2S in homocysteine-induced cardiodynamic effects in the isolated rat heart. The hearts were retrogradely perfused according to the Langendorff technique. The maximum and minimum rates of pressure in the left ventricle (dp/dt max, dp/dt min), systolic and diastolic left ventricular pressures (SLVP, DLVP), heart rate (HR), and coronary flow (CF) were measured. A spectrophotometrical method was used to measure the following oxidative stress markers: index of lipid peroxidation (thiobarbituric acid reactive substances, TBARS), nitrite level (NO2−), superoxide anion radicals (O2•−), and hydrogen peroxide (H2O2) concentrations. The administration of 10 µmol/l DL-homocysteine (DL-Hcy) alone decreased dp/dt max, SLVP, and CF but did not change any oxidative stress parameters. The administration of 10 µmol/l DL-propargylglycine (DL-PAG) decreased all cardiodynamic parameters and increased the concentration of O2•−. The co-administration of DL-Hcy and DL-PAG induced a significant decrease in all estimated cardiodynamic parameters and decreased the concentration of NO2− and O2•− but increased the levels of TBARS and H2O2. Homocysteine shows a lower pro-oxidative effect in the presence of hydrogen sulfide (H2S), which indicates a potential anti-oxidative capacity of H2S.


2020 ◽  
Vol 11 (1) ◽  
pp. 15-25
Author(s):  
N. S. Govorushkina ◽  
S. B. Bolevich ◽  
V. Jakovlevich ◽  
B. I. Tachieva ◽  
S. S. Bolevich ◽  
...  

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.


2018 ◽  
Vol 25 (3) ◽  
pp. 177 ◽  
Author(s):  
Vladimir Lj Jakovljevic ◽  
Anica Petkovic ◽  
Jovana Bradic ◽  
Jovana Jeremic ◽  
Tamara Nikolic Turnic ◽  
...  

2018 ◽  
Vol 19 (1) ◽  
pp. 11-16 ◽  
Author(s):  
Jelena Smigic ◽  
Isidora Stojic ◽  
Vladimir Zivkovic ◽  
Ivan Srejovic ◽  
Tamara Nikolic ◽  
...  

Abstract Taken into consideration that molecular and cellular mechanisms involved in cardiotoxicity are still not clear the aim of this study was to compare the production of oxidative stress parameters in the isolated rat heart between animals chronically treated with cisplatin and saline. The hearts of male Wistar albino rats (n = 24, 12 per group, age 8 weeks, body mass 250±50 g) were excised and perfused according to the Langendorff technique at gradually increased coronary perfusion pressures (40-120 cm H2O). We followed the production of superoxide anion radicals, hydrogen peroxide, and nitrites and also index of lipid peroxidation during the changes of coronary perfusion pressure (CPP) (from 40 to 120 cm H2O) in coronary venous effluent. Modifications CPP were performed in order to determined if oxidative stress is involved in coronary endothelium response in conditions of hypoxia (lower than 60 cm H2O) and hyperoxia (higher than 80 cm H2O). Based on the results of this research we can conclude that with enhancement of CPP the values of oxidative stress statistically increased. However, this increment is more prominent in control group as a result of preserved endothelium and its more powerful response to hyperoxia. On the other hand, damaged endothelium of cisplatin-treated animals had weaker response to hyperoxia, and also lower antioxidant capacity.


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