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

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.

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.


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):  
Babawande A. Origbemisoye ◽  
Badiu A. Akinbode ◽  
Ganiyat A. Oparemi

Monosodium glutamate (MSG) is a flavor enhancer. Its toxicity in a malnourished state appears not to have been fully investigated. This study was carried out to determine the effects of MSG on malnourished rats. Rats were randomly assigned into four groups of five rats/group. Group 1 rats were fed with malnourished feed; Group 2 rats received malnourished feed with dosed 1.6 mg/g MSG per body weight; Group 3 rats were fed with normal feed and dosed 1.6 mg/g MSG per body weight and Group 4 rats served as the control group (normal healthy rats) and were fed with normal feed for 28 days. After 28 days, the rats were sacrificed with the liver harvested and blood samples collected. Results from the study showed that malnourished rats had significantly lower levels of oxidative stress biomarkers including, anti-oxidants compared with the control. The levels of malondialldehyde concentration and xanthine oxidase activity were high in malnourished fed rats. Aspartate aminotransferase and alanine transaminase levels of malnourished and normal rats administered MSG were significantly low compared to the normal healthy suggesting that labialization occurs in liver leading to leakage of these enzymes from the liver to the serum. Malnourished rats showed significant decrease in body weight losing 48 grams after 28 days compared to malnourished and normal rats fed with MSG which recorded significant increase in body weight after 28 days adding 26 g and 42 g respectively.


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.


2019 ◽  
Vol 20 (4) ◽  
pp. 343-349 ◽  
Author(s):  
Natalia Govoruskina ◽  
Ivan Srejovic ◽  
Stefani Bolevich ◽  
Sergey Bolevich ◽  
Bella Tachieva ◽  
...  

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.


1988 ◽  
Vol 255 (6) ◽  
pp. H1468-H1475 ◽  
Author(s):  
S. Momomura ◽  
M. Iizuka ◽  
T. Serizawa ◽  
T. Sugimoto

To test the hypothesis that the rate of left ventricular relaxation can be dissociated from left ventricular stiffness, indexes of stiffness and relaxation were evaluated during mild hypoxia and hypoxia with isoproterenol or caffeine in isovolumically beating, isolated rat heart preparations. In group 1, the hearts were perfused with mild hypoxic buffer for 30 min. In group 2, 10 min of mild hypoxic perfusion was followed by 20 min of mild hypoxia plus isoproterenol (10(-6) M). In group 3, the hearts were perfused with mild hypoxic buffer for 10 min followed by 20 min of hypoxia plus caffeine (10(-3) M) perfusion. In group 1, left ventricular end-diastolic pressure (LVEDP) was elevated only slightly, and time constant of left ventricular relaxation T was also prolonged slightly. In group 2, LVEDP was higher, but T was much shorter than the corresponding values in group 1 (LVEDP, 18 +/- 4 mmHg; T, 31.4 +/- 3.4 ms). In group 3, T was more markedly prolonged, and LVEDP tended to be higher than in group 1. These results indicate that the determinants of left ventricular relaxation and stiffness are not identical and that in certain conditions relaxation can be separated from left ventricular stiffness.


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.


2017 ◽  
Vol 263 ◽  
pp. e137
Author(s):  
Ivan Srejovic ◽  
Vladimir Zivkovic ◽  
Nevena Jeremic ◽  
Isidora Stojic ◽  
Tamara Nikolic ◽  
...  

VASA ◽  
2020 ◽  
Vol 49 (4) ◽  
pp. 281-284
Author(s):  
Atıf Yolgosteren ◽  
Gencehan Kumtepe ◽  
Melda Payaslioglu ◽  
Cuneyt Ozakin

Summary. Background: Prosthetic vascular graft infection (PVGI) is a complication with high mortality. Cyanoacrylate (CA) is an adhesive which has been used in a number of surgical procedures. In this in-vivo study, we aimed to evaluate the relationship between PVGI and CA. Materials and methods: Thirty-two rats were equally divided into four groups. Pouch was formed on back of rats until deep fascia. In group 1, vascular graft with polyethyleneterephthalate (PET) was placed into pouch. In group 2, MRSA strain with a density of 1 ml 0.5 MacFarland was injected into pouch. In group 3, 1 cm 2 vascular graft with PET piece was placed into pouch and MRSA strain with a density of 1 ml 0.5 MacFarland was injected. In group 4, 1 cm 2 vascular graft with PET piece impregnated with N-butyl cyanoacrylate-based adhesive was placed and MRSA strain with a density of 1 ml 0.5 MacFarland was injected. All rats were scarified in 96th hour, culture samples were taken where intervention was performed and were evaluated microbiologically. Bacteria reproducing in each group were numerically evaluated based on colony-forming unit (CFU/ml) and compared by taking their average. Results: MRSA reproduction of 0 CFU/ml in group 1, of 1410 CFU/ml in group 2, of 180 200 CFU/ml in group 3 and of 625 300 CFU/ml in group 4 was present. A statistically significant difference was present between group 1 and group 4 (p < 0.01), between group 2 and group 4 (p < 0.01), between group 3 and group 4 (p < 0.05). In terms of reproduction, no statistically significant difference was found in group 1, group 2, group 3 in themselves. Conclusions: We observed that the rate of infection increased in the cyanoacyrylate group where cyanoacrylate was used. We think that surgeon should be more careful in using CA in vascular surgery.


Sign in / Sign up

Export Citation Format

Share Document