Репозиторий Университета

© 2020 Elsevier Inc. The hypothalamus is the most important integrator of autonomic and endocrine regulation in the body and it also has a fundamental role in ageing development and lifespan control. In order to better understand the role of NO-ergic system in the hypothalamic regulation of ageing, the purpose of this study was to investigate the expression of neuronal nitric oxide synthase (nNOS) in the arcuate (ARC), ventromedial (VMH) and dorsomedial (DMH) hypothalamic nuclei in young (2-3-month-old) and old (24-month-old) male and female rats using immunohistochemistry and western blot analysis. In young animals, only single nNOS-immunoreactive (IR) neurons were detected in ARC, and nNOS-IR neurons were found in the VMH (19 ± 3.2% in females and 14.5 ± 2.6% in males) and DMH (17 ± 4.0% in females and 21 ± 2.8% in males). In aged animals, the number of nNOS-IR neurons increased in all studied nuclei, including ARC (36 ± 3.1% in females and 33.5 ± 3.7% in males), VMH (83 ± 4.3% in females and 58 ± 2.1% in males) and DMH (57 ± 1.9% in females and 54 ± 1.8% in males). The expression of nNOS also significantly increased in the ARC, VMH and DMH during ageing by western blot analysis. In conclusion, ageing is accompanied by increasing of nNOS expression in the hypothalamus and this process is related to regions involved in the control of feeding behavior.

© 2019, Springer Science+Business Media, LLC, part of Springer Nature. Here, I present the data testifying that the conversion of free radical NO molecules to nitrosonium ions (NO+), which are necessary for the realization of one of NO biological effects (S-nitrosation), may occur in living organisms after binding NO molecules to loosely bound iron (Fe2+ ions) with the subsequent mutual one-electron oxidation–reduction of NO molecules (their disproportionation). Inclusion of thiol-containing substances as iron ligands into this process prevents hydrolysis of NO+ ions bound to iron thus providing the formation of stable dinitrosyl iron complexes (DNIC) with thiol ligands. Such complexes act in living organisms as donors of NO and NO+, providing stabilization and transfer of these agents via the autocrine and paracrine pathways. Without loosely bound iron (labile iron pool) and thiols participating in the DNIC formation, NO functioning as one of universal regulators of diverse metabolic processes would be impossible.

This study aimed to investigate the effects of propofol through evaluating its interaction with nitric oxide (NO), hydrogen sulfide (H2S), and carbon monoxide (CO). Wistar male rats were divided in 4 groups: (1) bolus injection of propofol (1% 10 mg/mL, 100 mg/kg bw, i.p.); (2) Nω-nitro-l-arginine methyl ester (L-NAME; NO synthase inhibitor, 60 mg/kg bw, i.p.) + bolus injection of propofol (1% 10 mg/mL, 100 mg/kg bw, i.p.); (3) DL-propargylglycine (DL-PAG; H2S synthase inhibitor, 50 mg/kg bw, i.p.) + bolus injection of propofol (1% 10 mg/mL, 100 mg/kg bw, i.p.); (4) zinc protoporphyrin IX (ZnPPIX; CO synthase inhibitor, 50 μmol/kg bw, i.p.) + bolus injection of propofol (1% 10 mg/mL, 100 mg/kg bw, i.p.). Increased levels of albumins, low-density lipoproteins, alkaline phosphatase, amylase, high-sensitivity Troponin T, and fibrinogen were found in L-NAME + propofol group. Platelet crit, platelet count, total cholesterol, and high-density lipoproteins were elevated in ZnPPIX + propofol group. Hydrogen peroxide was increased in all groups treated with gasotransmitters inhibitors. Reduced glutathione was reduced in all groups, superoxide dismutase activity only in L-NAME + propofol. The effect of propofol on various biochemical, haematological, and oxidative stress markers may be at least in part mediated through interaction with 3 estimated gasotransmitters.

© 2019, Spandidos Publications. All rights reserved. Adiponectin, endothelin and nitric oxide (NO) are major regulators of vascular function. An imbal-ance of vasoactive factors contributes to the onset and progression of atherosclerosis. Various single nucleotide polymorphisms (SNPs) are considered to be risk factors for coronary heart disease. However, the molecular mechanisms of their associations with the components of endothelial dysfunction are poorly understood. In the present study, rs17366743, rs17300539, rs266729, rs182052 and rs2241766 SNPs of the adiponectin (ADIPOQ) gene and rs2070699, rs1800542 and rs1800543 SNPs of the endothelin-1 (EDN1) gene were genotyped in 477 patients with coronary heart disease who were subjected to coronary angiography, in order to determine the presence or absence of coronary atherosclerosis. The serum levels of adiponectin, endothelin and stable metabolites of NO, (nitrate and nitrite NOx), were assayed and their associations with the SNP genotypes and coronary lesions were calculated. The results indicated that rs17366743 of the ADIPOQ gene and rs2070699 and rs1800543 of the EDN1 gene were associated with the levels of NOx in women, which in turn was associated with cardiovascular mortality. In men, rs182052 and rs266729 of the ADIPOQ gene were associated with adiponectin levels, whereas rs17366743 of the ADIPOQ gene was associated with endothelin levels. Additionally, these SNPs were indirectly associated with the prevalence of coronary lesions in men. Therefore, the tested SNPs can be considered potential risk factors that lead to imbalance of vasoactive mediators in a gender-specific manner and contribute to the development of clinical manifestations of atherosclerosis.

© 2018 Pharmascope Publications. All rights reserved. To study the function of the endothelium in conducting vascular pharmacological samples in normal and blocking the synthesis of nitric oxide by ultrasound examination of the velocity of central blood flow in the femoral artery in comparison with the changes in systemic hemodynamics and the linear velocity of microcirculatory flow using laser flowmetry. It was studied the parameters of the blood flow velocity (the maximum systolic and diastolic velocity, average systolic and diastolic velocity, Gosling index of pulsatility and resistance index by the Doppler ultrasound Minimax-Doppler-K), the parameters of central circulation ("Biopac-systems MP-150", AcqKnowledge 4.2, USA), and linear velocity of the microcirculatory flow of the musculus vastus medialis (Biopac MP-150, USA) in intact animals and rats with N-Ni-tro-L-arginine methyl ester (L-NAME) induced deficiency of nitric oxide. Quantitative evaluation of endothelial dysfunction in the conduct of pharmacological tests with endothelium-dependent (acetylcholine) and endothe-lium-independent (sodium nitroprusside) vasodilatation is most indicative in calculating the coefficient reflecting the ratio of vascular responses areas in intact rats with L-NAME induced deficiency of nitric oxide. Blood flow parameters (the maximum systolic velocity, the calculated difference between systolic and diastolic velocities) showed a high correlation, both with mean arterial pressure and a linear velocity of the microcirculatory flow. We conclude, that ultrasound Doppler were reflected in the systemic and local vascular response to the administration of vasodilators. It allows an assessment of endothelial function by using the Minimax-Doppler-K device.

© 2018 Osipov, Machneva, Buravlev and Vladimirov. The biological roles of heme and nonheme nitrosyl complexes in physiological and pathophysiological conditions as metabolic key players are considered in this study. Two main physiological functions of protein nitrosyl complexes are discussed-(1) a depot and potential source of free nitric oxide (NO) and (2) a controller of crucial metabolic processes. The first function is realized through the photolysis of nitrosyl complexes (of hemoglobin, cytochrome c, or mitochondrial iron-sulfur proteins). This reaction produces free NO and subsequent events are due to the NO physiological functions. The second function is implemented by the possibility of NO to bind heme and nonheme proteins and produce corresponding nitrosyl complexes. Enzyme nitrosyl complex formation usually results in the inhibition (or enhancement in the case of guanylate cyclase) of its enzymatic activity. Photolysis of protein nitrosyl complexes, in this case, will restore the original enzymatic activity. Thus, cytochrome c acquires peroxidase activity in the presence of anionic phospholipids, and this phenomenon can be assumed as a key step in the programmed cell death. Addition of NO induces the formation of cytochrome c nitrosyl complexes, inhibits its peroxidase activity, and hinders apoptotic reactions. In this case, photolysis of cytochrome c nitrosyl complexes will reactivate cytochrome c peroxidase activity and speed up apoptosis. Control of mitochondrial respiration by NO by formation or photolytic decay of iron-sulfur protein nitrosyl complexes is an effective instrument to modulate mitochondrial metabolism. These questions are under discussion in this study.

©2018 Osipov, Machneva, Buravlev and Vladimirov. The biological roles of heme and nonheme nitrosyl complexes in physiological and pathophysiological conditions as metabolic key players are considered in this study. Two main physiological functions of protein nitrosyl complexes are discussed-(1) a depot and potential source of free nitric oxide (NO) and (2) a controller of crucial metabolic processes. The first function is realized through the photolysis of nitrosyl complexes (of hemoglobin, cytochrome c, or mitochondrial iron-sulfur proteins). This reaction produces free NO and subsequent events are due to the NO physiological functions. The second function is implemented by the possibility of NO to bind heme and nonheme proteins and produce corresponding nitrosyl complexes. Enzyme nitrosyl complex formation usually results in the inhibition (or enhancement in the case of guanylate cyclase) of its enzymatic activity. Photolysis of protein nitrosyl complexes, in this case, will restore the original enzymatic activity. Thus, cytochrome c acquires peroxidase activity in the presence of anionic phospholipids, and this phenomenon can be assumed as a key step in the programmed cell death. Addition of NO induces the formation of cytochrome c nitrosyl complexes, inhibits its peroxidase activity, and hinders apoptotic reactions. In this case, photolysis of cytochrome c nitrosyl complexes will reactivate cytochrome c peroxidase activity and speed up apoptosis. Control of mitochondrial respiration by NO by formation or photolytic decay of iron-sulfur protein nitrosyl complexes is an effective instrument to modulate mitochondrial metabolism. These questions are under discussion in this study.

© 2017 This work is aimed at exhaustive and detailed study of chemical, physical and physico-chemical characteristics of NO-containing gas flow (NO-CGF) generated by a plasma-chemical generator of Plason device, which has been used in medical practice for more than 15 years for effectively healing wound and inflammatory conditions with exogenous nitric oxide (NO-therapy). Data was obtained on spatial structure of the gas flow, and values of its local parameters in axial and radial directions, such as nitric oxide content, velocity, temperature and mass flow density of nitric oxide, providing altogether the effectiveness of treatment by the exogenous NO-therapy method, were determined experimentally and by computations. It was demonstrated that plasma-chemical synthesis of NO from atmospheric air in a low direct current (DC) arc provides a high mass flow of nitric oxide at the level of 1.6–1.8 mg/s, while in the area of impact of NO-CGF on the biological tissue, on its axis, NO content is 400–600 ppm, flow velocity about 5 m/s, nitric oxide mass flow density 0.25–0.40 mg/(s·cm2), temperature 40-60 °C. Tendencies were determined for designing new devices for further experimental biological and medical research in the field of NO-therapy: lowering the temperature of NO-CGF to ambient temperature will enable variation, in experiments, of the affecting flow parameters in a wide range up to their maximum values: NO content up to 2000 ppm, velocity up to 20 m/s, nitric oxide mass flow density up to 2.5 mg/(s·cm2).

© 2018, Silicea-Poligraf. All rights reserved. Aim. Assessment of prognostic significance of endothelial dysfunction markers: stable metabolites of nitric oxide (NOx), von Willebrand factor (vWF), endothelin-1 (E1), homocysteine and tissue plasminogen activator (tPA) in essential hypertension (EAH) patients not taking antihypertension therapy systematically. Material and methods. Totally, 12 EAH patients investigated (45 males, 79 females) (mean age 51,4±6,5 y.o., mean duration of AH 7,9±7,3 y.). Concentration of NOx in plasma was measured by spectrophotometry, and of vWF, homocysteine, E1 and tPA — by immune enzyme assay. Results. By the increase of SCORE risk level, there was significant increase of concentrations of NOx, E1, homocysteine and vWF in EAH patients (p<0,05), there were no changes in tPA levels (p>0,05). In 8 (8±1,1) years after baseline assessment, 115 patients were assessed second time. Of those 13 (11,3%) had cardiovascular events (CVE) and 5 (4,3%) died. By single factorial regression, the rate of CVE in EAH patients relate to homocystein level (р=0,01), NOx (р=0,001) and vWF (р=0,001). By multifactorial analysis, prognostic statistical significance is found for NOx (relative risk (RR) =3,8, р=0,006) and vWF (RR =3,5, р=0,005). In ROC-analysis there were found threshold levels of NOx (>46,6 mcM/L, AUC =0,863) and vWF (>1,68 mg/dL, AUC =0,738), the increase of which is followed by CVE development risk for the levels of NOx >46,6 mcM/L 3,8 times (sensitivity 81,9% and specificity 65,8%), vWF >1,68 mg/dL — 3,5 times (sensitivity 74,3% and specificity 62,7%). Combination of the parameters point on the risk increase up to 6,5 times (р=0,00007). Conclusion. NOx with the threshold of >46,6 mcM/L (RR =3,8) and vWF >1,68 mg/dL (RR =3,5) do show independent prognostic value for 5-year CVE risk assessment in EAH patients that can be applied as an additional method for risk stratification to estimate a group for more aggressive therapy and CVE prevention.

© 2018 Vserossiiskoe Obshchestvo Kardiologov. All rights reserved. Aim. Assessment of the markers levels of endothelial dysfunction (ED): stable metabolites of nitric oxide (NOx), endothelin-1 (E1), homocysteine (HC), von Willebrand factor (vWF) and tissue plasminogen activator (tPA) in blood plasma of smoker and nonsmoker patients with arterial hypertension (AH) of low and moderate risk, not taking antihypertension therapy regularly. Material and methods. Totally, 124 AH patients included, 45 males and 79 females, mean age 51,4±6,5 y. O., mean AH duration 7,9±7,3 y. Controls included 35 healthy volunteers (20 males, 15 females). Concentration of NOx in plasma was measured with spectrophotometry, and of vWF, HC, E1 and tPA-with immune enzyme assay. Results. To evaluate the relation of smoking and ED markers levels, AH patients and controls were selected to subgroups according to smoking status: smoker (35,5%) and non-smoker (64,5%) AH patients; smoker (38%) and non-smoker (62%) controls. In smoker AH patients comparing to non-smoking there were significantly higher concentrations of NOx-48,2±18,8 mcM/L and 40,3±21,2 mcM/L, respectively (p<0,05), E1-1,2±0,16 and 0,6±0,2 fM/L, resp. (p<0,05), HC-25,7±6,04 and 16,2±6,5 mcM/L, resp. (p<0,05), vWF-1,39±0,7 and 1,1±0,6 mg/dL, resp (p<0,05) and tPA-13,05±6,2 and 8,5±6,2 mcM/L, resp. (p<0,05). There was correlation in the AH group, of NOx concentration and smoking (r=0,46, p<0,05), and tobacco smoking duration (r=0,83, p<0,05). Also, there were positive correlations of HC and smoking (r=0,4, p<0,05). In control group smokers had higher HC-20,7±5,3 and 17,2±4,7 mcM/L, resp. (p<0,05), vWF-1,3±0,8 and 0,8±0,6 mg/dL, resp. (p<0,05) and tPA-11,1±6,5 and 6,6±5,2 mcM/L, resp. (p<0,05). There were no significant changes in NOx and E1. Conclusion. In smokers of both AH and control groups the levels of HC, vWF and tPA were significantly higher in comparison with nonsmokers. In smoker AH patients the mean concentrations of NOx and E1 are higher than in non-smoker patients. Levels of ED are related with not only the fact of smoking itself (p<0,05), but smoking duration (p<0,05).