scholarly journals Correction of morphofunctional disorders of the cardiovascular system with asialized erythropoietin and arginase II selective inhibitors KUD 974 and KUD 259 in experimental preeclampsia

2020 ◽  
Vol 6 (1) ◽  
pp. 29-40 ◽  
Author(s):  
Tatyana I. Lokteva ◽  
l’ya S. Rozhkov ◽  
Vladimir V. Gureev ◽  
Anastasia V. Gureeva ◽  
Marija A. Zatolokina ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Endothelial Dysfunction ◽  
Cardiovascular System ◽  
Pressure Coefficient ◽  
Selective Inhibitor ◽  
Selective Inhibitors ◽  
Fluid Content ◽  
Positive Effects ◽  
Female Wistar Rats ◽  
Arginase Ii

Introduction: Preeclampsia remains one of the most common causes of maternal and perinatal mortality worldwide. A significant role in the pathogenesis of this pathology is assigned to placental ischemia and endothelial dysfunction. Therefore, the aim of the present study was to study the effectiveness of asialized erythropoietin and arginase II selective inhibitors: KUD-259 and KUD-974 in the correction of morphofunctional disorders of the cardiovascular system in experimental preeclampsia. Materials and methods: The study was performed in 260 female Wistar rats, each weighing 250–300 g. An ADMA-like preeclampsia was reproduced in the experiment. To assess the emerging morphofunctional disorders, the following parameters were used: blood pressure, coefficient of endothelial dysfunction, microcirculation in the placenta, proteinuria, fluid content in the omentum, concentration of terminal metabolites in the blood plasma, and morphometric parameters of fetuses. Results and discussion: The administration of arginase II selective inhibitor KUD-974 in combination with asialized erythropoietin leads to a pronounced correction of emerging changes: a decrease in systolic and diastolic blood pressure in 1.5 and 1.7 times, a decrease in proteinuria in 3.6 times and a decrease in fluid content in the omentum. When arginase II selective inhibitor KUD 974 and asialized erythropoietin are used with methyldopa, the positive effects of the former are enhanced. Conclusion: Arginase II selective inhibitors KUD-259 and KUD-974 and asialized erythropoietin have a pronounced positive effect on the correction of morphofunctional disorders in animals with ADMA-like preeclampsia.

scholarly journals Study of the effect of selective inhibitor of Arginase II KUD 975 and of low doses of Acetylsalicylic acid on the functional parameters of the cardiovascular system In experimental preeclampsia

2019 ◽  
Vol 5 (4) ◽  
pp. 47-56 ◽  
Author(s):  
Olga V. Severinova ◽  
Vladimir V. Gureev ◽  
Lyudmila A. Zhilinkova ◽  
Galina A. Lazareva ◽  
Anastasia V. Gureeva ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Acetylsalicylic Acid ◽  
Pregnant Women ◽  
Diastolic Blood Pressure ◽  
Selective Inhibitor ◽  
Greater Omentum ◽  
Female Wistar Rats ◽  
Obstetric Morbidity ◽  
Arginase Ii ◽  
Positive Effect

Introduction: Over the past decade, preeclampsia has been the subject of an increased attention, as this complication is the most common cause of maternal mortality, triggering every third case of obstetric morbidity and taking lives of up to 50.000 young women worldwide each year. Despite a large number of ongoing studies, no clear algorithm for monitoring pregnant women with this pathology has been developed yet. Materials and methods: The study was conducted on 220 female Wistar rats weighing 250–300 g. In the experiment, ADMA-like preeclampsia model was used. Results and discussion: The introduction of L-NAME to the animals from the 14th till the 20th day of pregnancy causes the following disturbances: a rise in systolic and diastolic blood pressure in 1.4 and 1.5 times, an increase in proteinuria in 3.3 times and an increase in the content of fluid in the greater omentum from 44.39 ± 1.62% to 55.02 ± 1.74%, all of which correspond to the disorders in pregnant women in case of preeclampsia. The use of the selective inhibitor of arginase II KUD 975 (3mg/kg/day) in combination with acetylsalicylic acid (10mg/kg/day) leads to a pronounced correction in the emerging changes: a decrease in systolic and diastolic blood pressure in 1.2 and 1.3 times, a decrease in proteinuria in 1.9 times and a decrease in the fluid content in the greater omentum. Conclusion: Selective inhibitor of arginase II KUD 975 and small doses of acetylsalicylic acid have a pronounced positive effect in the correction of morphofunctional disorders in animals with ADMA-like preeclampsia.

scholarly journals Correction of morphofunctional disturbances arising when modelling Preeclampsia with resveratrol and nicorandil

2018 ◽  
Vol 4 (1) ◽  
pp. 59-71 ◽  
Author(s):  
Elena G. Stupakova ◽  
Galina A. Lazareva ◽  
Vladimir V. Gureev
Keyword(s):  
Blood Pressure ◽  
Endothelial Dysfunction ◽  
Diastolic Blood Pressure ◽  
Morphometric Parameters ◽  
New Drugs ◽  
Fluid Content ◽  
Positive Effects ◽  
Urgent Task ◽  
Positive Effect ◽  
Morphological State

Introduction: Preeclampsia is one of the most serious diseases of the second half of pregnancy and is surely amongst the top three causes of maternal mortality. Therefore, the creation of new drugs for preventing and correcting preeclampsia is an urgent task. Methods: In the experiment, an ADMA-like L-NAME-induced model of preeclampsia was reproduced. To assess the emerging morphofunctional disorders, the following parameters were used: blood pressure, endothelial dysfunction coefficient, microcirculation in the placenta, proteinuria, fluid content in the large omentum, concentration of terminal metabolites in the blood plasma, morphological state of the placenta and kidneys and morphometric parameters of the foetus. Results and Discussion: Injection of L-NAME into the animals from the 14th to the 20th day of pregnancy causes disorders: an increase in systolic and diastolic blood pressure by 1.4 and 1.5 times, an increase in proteinuria by 3.3 times and an increase in the fluid content in a large omentum from 45.82 ± 1.82% to 54.73 ± 1.96%, which correspond to disorders due to preeclampsia in pregnant women. There was also a disturbance of endothelial function, as evidenced by an increase in the coefficient of endothelial dysfunction (CED) by 2.9 times. The use of resveratrol leads to a pronounced correction in the changes that occur: a decrease in systolic and diastolic arterial pressure by 1.2 and 1.3 times, a decrease in proteinuria by a factor of 1.9 and a decrease in the fluid content in the large omentum to 50.00 ± 1.25%. The use of nicorandil leads to a pronounced correction in the resulting changes: a decrease in the diastolic blood pressure by 1.14 times, a decrease in proteinuria by a factor of 1.7 and a decrease in the fluid content in the large omentum to 50.57 ± 2.08%. CED decreased 1.7 times. When combining their use with amlodipine, the positive effects increased: systolic and diastolic blood pressure decreased 1.13 and 1.24 times and 1.14 and 1.23 times, respectively, proteinuria decreased 2.7 and 2.3 times, the fluid content in the large omentum was reduced to 44.54 ± 1.80% and 46.73 ± 1.30%. CED decreased 1.7 and 2.3 times. The administration of glibenclamide together with resveratrol and nicorandil removes a significant part of their positive effects. Conclusion: Resveratrol and nicorandil have a significant positive effect in the correction of morphofunctional disorders in animals with ADMA-like preeclampsia. Activation of K+ATP channels plays a significant role in the realisation of their positive effects.

scholarly journals Correction of morphofunctional disorders with asialoerythropoietin and selective inhibitor of arginase II KUD975 in cases of ischemic kidney damage in the experiment

2018 ◽  
Vol 4 (4) ◽  
pp. 29-40
Author(s):  
Vladislav Elagin ◽  
Oleg Bratchikov ◽  
Maria Zatolokina
Keyword(s):  
Selective Inhibitor ◽  
Kidney Damage ◽  
Pharmacological Agents ◽  
Positive Effects ◽  
Ischemic Reperfusion ◽  
Leading Role ◽  
Reperfusion Damage ◽  
Combined Use ◽  
Fractional Excretion Of Sodium ◽  
Arginase Ii

Introduction: Acute kidney injury (AKI), which is based on ischemic-reperfusion damage, is a widespread life-threatening condition and remains a serious public health problem with a high mortality rate among patients. Despite significant advances in various areas of medicine, the prevention and correction of ischemic-reperfusion kidney damage are still far from being at the desired level. Pharmacological preconditioning and the use of endothelioprotectors are promising areas in this field, therefore the purpose of this study was to analyze the nephroprotective properties of asialoerythropoietin and selective inhibitor of arginase II KUD975 in ischemic kidney damage in the experiment. Materials and methods: The study was performed on 260 white adult male Wistar rats, each weighing 180-220 g. Ischemic-reperfusion damage was simulated by applying a clamp on the renal leg for 40 minutes. To determine a degree of correction caused by morphofunctional disorders traditional functional, biochemical and morphological criteria were used. Results and discussion: When administering asialoerythropoietin and selective inhibitor of arginase II KUD975, there is observed an improvement in the glomerular filtration and microcirculation in the kidneys, decrease in the concentration of creatinine and urea, a decrease in fractional excretion of sodium and improvement in the histological pattern at different periods. The most pronounced nephroprotective effects are observed in the combined use of the test pharmacological agents, which are superior to such used in a monotherapy. The use of glibenclamide and L-NAME against the background of the correction of the pathology caused by asialoerythropoietin completely eliminates its positive effects. When glibenclamide and L-NAME are used against the background of correction of the pathology caused by the selective inhibitor of arginase II KUD975, its positive effects are completely eliminated by L-NAME. Glibenclamide does not eliminate positive effects. Conclusions: The results of the experiment prove the presence of pronounced nephroprotective properties of asialoerythropoietin and selective inhibitor of arginase II KUD975 in ischemic kidney damage in the experiment. The most pronounced effects are observed in the combined use of these pharmacological agents. The leading role in causing the positive effects from asialoerythropoietin is played by the activation of K+ATP channels and the activation of eNOS. The leading role in causing the positive effects from the selective inhibitor of arginase II KUD975 is played by the activation of eNOS.

scholarly journals STUDY OF THE PHARMACOLOGICAL ACTIVITY OF LOWMOLECULAR ARGINASE II SELECTIVE INHIBITOR USING A MODEL OF MONOCROTALINE-INDUCED PULMONARY HYPERTENSION

2019 ◽  
Vol 26 (1) ◽  
pp. 114-121 ◽  
Author(s):  
Liliya V. Korokina ◽  
Mikhail V. Pokrovskii ◽  
Leonid V. Pazhinskii ◽  
Indira S. Kochkarova ◽  
Mikhail V. Korokin
Keyword(s):  
Pulmonary Hypertension ◽  
Endothelial Dysfunction ◽  
Right Ventricle ◽  
Pharmacological Activity ◽  
Conflict Of Interest ◽  
Selective Inhibitor ◽  
Molecular Compound ◽  
Contraction Rate ◽  
Male Wistar Rats ◽  
Arginase Ii

The aimof the present work was to study the pharmacological activity of a low-molecular arginase II selective inhibitor (low-molecular compound with laboratory code ZB49) with the chemical formula 2-{1-[3-(3-[chloroisoxazole-5-yl) propyl] piperidin-4-yl}-6-(digibroxyboryl) norleucine dihydrochloride) using a model of monocrotaline-induced pulmonary hypertensionMaterials and methods.The work was performed on 40 adult male Wistar rats weighing 180– 220 g. The simulation of monocrotaline pulmonary hypertension was performed on 20 animals using a subcutaneous injection of an alcohol-aqueous solution of monocrotaline (MCT) at a dose of 60 mg/kg in a volume of 0.5 ml per animal. 7 days after the MCT injection, the administration of the studied pharmaceutical substance (PS) (laboratory code ZB49) was started at a dose of 5 mg/kg. ZB49 was administered intragastrically, once a day with the administration duration of 21 days.Results.Under the intragastric FS ZB49 administration at a dose of 5 mg/kg, a statistically significant decrease in the coefficient of endothelial dysfunction, systolic right ventricle pressure (SRVP), average the right ventricle pressure (ARVP), diastolic right ventricle pressure (DRVP), maximum contraction rate (dP/dt max) and minimum contraction rate (dP/dt min) was established at the background of the simulation of monocrotaline-induced pulmonary hypertension. At the same time, a statistically significant positive effect of ZB49 on the blood gas composition was established.Conclusion.The study has confirmed the possibility of using arginase inhibitors to prevent the development of endothelial dysfunction and the disorders of nitric oxide metabolism in pulmonary arterial hypertension. Among the substances of this group, arginase II selective inhibitors should be considered as the most promising.Conflict of interest: the authors declare no conflict of interest.

scholarly journals Transmission of raised blood pressure and endothelial dysfunction to the F2generation induced by maternal protein restriction in the F0, in the absence of dietary challenge in the F1generation

2008 ◽  
Vol 100 (4) ◽  
pp. 760-766 ◽  
Author(s):  
Christopher Torrens ◽  
Lucilla Poston ◽  
Mark A. Hanson
Keyword(s):  
Blood Pressure ◽  
Endothelial Dysfunction ◽  
Vascular Function ◽  
Protein Restriction ◽  
Mesenteric Arteries ◽  
Maximal Response ◽  
Maternal Line ◽  
Maternal Protein Restriction ◽  
Female Wistar Rats ◽  
Protein Restricted Diet

We have previously demonstrated that maternal protein restriction during pregnancy leads to raised blood pressure and endothelial dysfunction in the offspring (F1). Here we show that these characteristics are transmitted to the F2offspring through the maternal line, in the absence of any additional challenges to the F1. Female Wistar rats were fed either a control (18 % casein) or protein-restricted diet (PR; 9 % casein) throughout pregnancy. Female F1offspring, maintained on standard chow postpartum, were mated with breeding males to produce F2progeny. Systolic blood pressure (SBP) in male F2offspring was assessed by tail-cuff plethysmography at age 100 d and vascular function of small mesenteric arteries by wire myography at age 80 and 200 d. SBP was raised in PR F2offspring compared with controls (control 122·1 (sem2·3) mmHg,n7; PR 134·7 (sem3·2) mmHg,n6;P < 0·01) and endothelial function, assessed by vasodilatation to acetylcholine, was impaired at both age 80 d (% maximal response: control 89·7 (sem2·6),n14; PR 72·7 (sem4·4),n15;P < 0·01) and 200 d (effective concentration equal to 50 % of maximum (pEC50): control 7·67 (sem0·10),n10; PR 7·33 (sem0·07),n8;P < 0·05). The present study demonstrates that both raised blood pressure and endothelial dysfunction are passed via the maternal line to grand-offspring in the absence of any additional dietary challenges to their F1mothers. Risk factors for chronic disease may therefore be heritable by non-genomic processes.

scholarly journals CORRECTION OF MORPHOFUNCTIONAL DISORDERS IN EXPERIMENTAL PREECLAMPSY BY COMBINED USE OF TRIMETAZIDINE AND PURIFIED MICRONIZED FLAVONOID FRACTION AS WELL AS THEIR COMBINATIONS WITH METHYLAMPSY

2021 ◽  
Vol 8 (5) ◽  
pp. 304-315
Author(s):  
O. E. Antsiferova ◽  
M. P. Teleshchenko ◽  
Yu. M. Tsuverkalova ◽  
M. V. Pokrovsky ◽  
V. V. Gureev ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Endothelial Dysfunction ◽  
Research University ◽  
New Drugs ◽  
Greater Omentum ◽  
Functional Disorders ◽  
Urgent Task ◽  
Combined Use ◽  
Female Wistar Rats ◽  
Flavonoid Fraction

The aim of the experiment was to determine the effectiveness of the combined use of trimetazidine and a purified micronized flavonoid fraction, as well as their combinations with methyldopa, in comparison with monotherapy with the same drugs in the correction of morphofunctional disorders arising in the conditions of experimental preeclampsia. An integrated/multimethodology approach is the most effective way of treatment for preeclampsia. Therefore, an urgent task of modern pharmacology is to study the effectiveness of new drugs when used in combinations, as well as the drugs included in the standards for treatment.Materials and methods. The study was carried out at the Research Institute of Pharmacology of Living Systems of Belgorod State National Research University. The experiment was performed on 200 female Wistar rats, weighing 250–300 g, in which an ADMA-like model of preeclampsia had been reproduced. To assess the degree of correction of emerging morphological and functional disorders, the following parameters were involved: blood pressure, a coefficient of endothelial dysfunction, microcirculation in the placenta, proteinuria, fluid contents in the greater omentum, morphometric indicators of placental tissues and fetal height and weight parameters.Results. The combined use of trimetazidine (Preductal® MB) 6 mg/kg and a purified micronized flavonoid fraction (Detralex®) 260 mg/kg, as well as their combination with methyldopa (Dopegit®) 86 mg/kg, leads to a more pronounced decrease in the blood pressure, compared with a decrease in the coefficient of endothelial dysfunction by 2.22, 2.19 and 1.94 times, respectively, in relation to “untreated” animals. There was an increase in microcirculation indices in the placenta by 2.35, 2.21 and 2.03 times, respectively. In addition, there was an improvement in morphological parameters in the placenta and fetuses.Conclusion. The results of the study showed a greater effectiveness of the combined use of the studied drugs in experimental preeclampsia compared to their monotherapy. This indicates the prospects for the use of trimetazidine and purified micronized flavonoid fraction in the complex therapy for preeclampsia and the need for further research in this direction.

Caffeine and Placebo Expectation

2007 ◽  
Vol 21 (2) ◽  
pp. 91-99 ◽  
Author(s):  
Yunfeng Sun ◽  
Yinling Zhang ◽  
Ning He ◽  
Xufeng Liu ◽  
Danmin Miao
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Sleep Deprivation ◽  
Cognitive Performance ◽  
Cognitive Functions ◽  
Cardiovascular Regulation ◽  
Double Blind ◽  
Positive Effects ◽  
Pressure Tests ◽  
Healthy Males

Abstract. Caffeine placebo expectation seems to improve vigilance and cognitive performance. This study investigated the effect of caffeine and placebo expectation on vigilance and cognitive performance during 28 h sleep deprivation. Ten healthy males volunteered to take part in the double-blind, cross-over study, which required participants to complete five treatment periods of 28 h separated by 1-week wash-out intervals. The treatments were no substance (Control); caffeine 200 mg at 00:00 (C200); placebo 200 mg at 00:00 (P200); twice caffeine 200 mg at 00:00 and 04:00 (C200-C200); caffeine 200 mg at 00:00 and placebo 200 mg at 04:00 (C200-P200). Participants were told that all capsules were caffeine and given information about the effects of caffeine to increase expectation. Vigilance was assessed by a three-letter cancellation test, cognitive functions by the continuous addition test and Stroop test, and cardiovascular regulation by heart rate and blood pressure. Tests were performed bihourly from 00:00 to 10:00 of the second day. Results indicated that C200-P200 and C200-C200 were more alert (p < .05) than Control and P200. Their cognitive functions were higher (p < .05) than Control and P200. Also, C200-P200 scored higher than C200 in the letter cancellation task (p < .05). No test showed any significant differences between C200-P200 and C200-C200. The results demonstrated that the combination of caffeine 200 mg and placebo 200 mg expectation exerted prolonged positive effects on vigilance and cognitive performance.

Bifurcation in a Simple Model of the Cardiovascular System

2000 ◽  
Vol 39 (02) ◽  
pp. 118-121 ◽  
Author(s):  
S. Akselrod ◽  
S. Eyal
Keyword(s):  
Nonlinear Dynamics ◽  
Blood Pressure ◽  
Heart Rate ◽  
Fixed Point ◽  
Cardiovascular System ◽  
Modified Model ◽  
Mayer Waves ◽  
Sustained Oscillations ◽  
Human Cardiovascular System ◽  
Physiological Values

Abstract:A simple nonlinear beat-to-beat model of the human cardiovascular system has been studied. The model, introduced by DeBoer et al. was a simplified linearized version. We present a modified model which allows to investigate the nonlinear dynamics of the cardiovascular system. We found that an increase in the -sympathetic gain, via a Hopf bifurcation, leads to sustained oscillations both in heart rate and blood pressure variables at about 0.1 Hz (Mayer waves). Similar oscillations were observed when increasing the -sympathetic gain or decreasing the vagal gain. Further changes of the gains, even beyond reasonable physiological values, did not reveal another bifurcation. The dynamics observed were thus either fixed point or limit cycle. Introducing respiration into the model showed entrainment between the respiration frequency and the Mayer waves.

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