Concentration Of NO Metabolites Research Articles

Blood Level of Nitric Oxide Metabolites and Expression of Genes Regulating NO Synthesis in Early Forms of Non-Alcoholic Fatty Liver Disease.

The levels of NO metabolites in the plasma and mRNA of the NOS3, ATG9B, and NOS2 genes in peripheral blood leukocytes of healthy people and patients with early forms of non-alcoholic fatty liver disease (steatosis and weak activity non-alcoholic steatohepatitis) were studied. In patients with steatohepatitis, the concentration of NO metabolites in the blood and the level of mRNA of the NOS2 gene were higher than in patients with steatosis and healthy people. These differences can be of diagnostic value for distinguishing between steatosis and weak activity steatohepatitis in non-alcoholic fatty liver disease. A correlation between the levels of NO metabolites and the expression of the NOS2 gene in weak activity steatohepatitis was established, which indicates activation of NO synthesis in non-alcoholic steatohepatitis due to the expression of the inducible NO synthase gene. The level of the NOS2 gene mRNA in peripheral blood leukocytes of patients with weak activity steatohepatitis correlated with the level of TNFα and IL-6 cytokines. An increase in the level of NO in the blood in weak activity steatohepatitis correlated with the level of MDA, an indicator of oxidative stress.

The Antioxidant Effect of Mitochondrially Targeted Antioxidant SkQ1 on the Isolated Rat Heart Model

Mitochondrially targeted antioxidants based on Skulachev ions (SkQ1) are extremely attractive for neutralizing reactive oxygen species directly in the mitochondrial matrix.The aim was to examine the antioxidant and cardioprotective status of the SkQ1 mitochondrially targeted antioxidant in an isolated rat heart model of ischemia and reperfusion after cold cardioplegia.Material and methods. The effects of different concentrations of SkQ1 (1200 ng/ml, 120 ng/ml, 12 ng/ml) were explored on isolated hearts of Wistar rats (n=50) during 240-min cold cardioplegia. The levels of oxidative stress, changes in myocardial damage markers (classical and highly specific) and cardiac function (coronary flow velocity, heart rate, systolic pressure) were assessed.Results. The use of SkQ1 at 12 ng/ml resulted in a significant neutralization of oxidative stress manifestations (P<0.05). The minimum concentration of NO metabolites (nitrates and nitrites) (36.2 [30.8; 39.8] µmol/ml) was maintained at pre-ischemic level throughout the 30-minute reperfusion period, while the malonic dialdehyde concentration (49.5 [41.1; 58.9] µmol/g) was lower compared with SkQ1 use at 120 ng/ml dose. Due to the «mitigation» of oxidative stress, intracellular enzymes and highly specific markers of myocardial damage rose more slowly during reperfusion, while cardiac function recovery occurred at a higher rate and showed stability upon restoration of perfusion.Conclusion. SkQ1 at 12 ng/ml concentration showed strong antioxidant and cardioprotective properties in an ex vivo study.

Алельний поліморфізм гена eNOS у дітей, які страждають від бронхіальної астми, за еозинофільного та пауцигранулоцитарного субтипу запалення бронхів

Метою роботи було вивчити вплив алельного поліморфізму гена eNOS, що кодує активність ендотеліальної NO-синтази та синтез монооксиду нітрогену в дихальних шляхах, на окремі клінічно-параклінічні показники бронхіальної астми в дітей шкільного віку за еозинофільного і пауцигранулоцитарного запального фенотипу. Обстежені 22 хворі на бронхіальну астму з еозинофільним характером запалення дихальних шляхів та 15 пацієнтів — із пауцигранулоцитарним. Проведено імунологічні, спірометричні дослідження, генотипування ендотеліальної NOS.Тяжкість бронхіальної астми у хворих із різним типом запалення бронхів суттєво не залежить від алельного поліморфізму гена eNOS. Відсутність мутацій гена eNOS у вигляді генотипу GG виявилася характернішою для хворих із пауцигранулоцитарним характером запалення бронхів, алельний поліморфізм GT/TT — для дітей з еозинофільним запаленням. За наявності алельного поліморфізму гена eNOS за генотипу GT/TT дітям із пауцигранулоцитарним характером запалення бронхів були притаманні частіші клінічні прояви атопічного дерматиту й алергічного риніту, більший індекс лабільності бронхів та нижча концентрація метаболітів NO в конденсаті повітря, що видихається.

Ambulatory Blood Pressure Monitoring and Endothelial Dysfunction in Hypertensive Patients with Diabetes Mellitus Type 2

Aim: Diabetic hypertensive patients have pronounced changes in ambulatory blood pressure profile and endothelial function. But the correlation between the parameters of ambulatory blood pressure monitoring (ABPM) and endothelial dysfunction in diabetic hypertensive patients have not been fully clarified. We studied ABP and endothelial function in a group of diabetic hypertensive patients. Methods: Patients with a glomerular filtration rate (GFR) of less than 30 mL/min per 1.73 m(2) were excluded. 120 patients were included into the research. Of these, the first (basic) group made up diabetic hypertensive patients in which there were 34 males and 26 females, the mean age was 56.1±1.3 years, the duration of arterial hypertension (AH) was 12.3±2.1 years and the duration of type 2 diabetes mellitus (DM2) was 4.4±0,7 years. The second (control) group made up 60 non-diabetic hypertensive patients in which there were 27 males and 33 females, the mean age was 55.2±1.2 year and duration of AH was 11.1±0.9 years. The patients in both groups were similar in age, duration of AH. Results:The analysis of the results of the 24-hour ABPM revealed that the number of patients with increased 24 hour systolic blood pressure (SBP) and diastolic blood pressure (DBP) variability was more among diabetic hypertensive patients than in non-diabetic hypertensive patients (76.7 % versus 21.1 and 70.0 % versus 22.5 %, respectively, p <0,05). There were not any significant changes in pulse rate, SBP and DBP. The amount of non-dipper and night-peaker patients was significantly higher in the basic group than in the control one (60.0 % versus 25.4 %, respectively, p <0,05). It was established that the number of patients with DBP daily value <10 was more significant in diabetic hypertensive patients versus non- diabetic hypertensive patients (33.3 % versus 18.2 %, respectively). We also determined nitric oxide metabolites concentration (nitrites and nitrates (NO)) and endothelin (ET-1) in serum and in 24 h-urine collection to assess endothelial function. So, the concentration of ET-1 in serum was significantly higher in diabetic hypertensive patients compared with non-diabetic hypertensive patients (2.49±0.01 pg/ml versus 1.5±0.07 pg/ml, respectively, p <0,05). NO metabolites concentration in serum and urine was significantly lower in the basic group than in the control group (12.7±1.5 uM versus 19,9±1,8 uM and 428.2±27.9 uM versus 792.1±39.4 uM, respectively, p <0,05). The direct association between SBP, DBP and ET-1 in urine were determined in diabetic hypertensive patients (r = 0.7, r = 0.99, respectively, p < 0.001). The correlation between daily index of SBP and ET-1 in urine (r = -0.58, p < 0.001), daily index of DBP and ET-1 in serum (r = -0.47, p < 0.001) were established in the basic group. Conclusion: The correlation between the parameters of ABPM and endothelial dysfunction in diabetic hypertensive patients were established in this study.

Beet on Alps: Time-course changes of plasma nitrate and nitrite concentrations during acclimatization to high-altitude

Nitric oxide seems to be involved in the altitude acclimatization process due to its ability to regulate pulmonary, cardiovascular and muscular responses to hypoxia. In this study, we investigated the plasma nitrate (NO3−) and nitrite (NO2−) response to hypobaric hypoxia in two groups of lowlanders exposed at different altitudes.For seven days, fourteen subjects were evaluated at Casati Hut (3269 m a.s.l. M.CEVEDALE) and eleven individuals were studied at Capanna Regina Margherita (4554 m a.s.l. M.ROSA). Before expeditions and at different time points during high-altitude sojourn, plasma NO3− and NO2− concentrations were measured by chemiluminescence. Resting peripheral arterial oxygen saturation (SpO2), heart rate (HR) and mean arterial blood pressure (MAP) were monitored during the experimental period. Possible confounding factors such as dietary NO3− intake, physical activity and altitude changes were controlled.Sea level plasma NO3− and NO2− concentrations significantly increased at altitude in both M.CEVEDALE group (+26.2 μM, p ≤ 0.0001, 95% CI [+17.6, +34.8] and +559.2 nM, p ≤ 0.0001, [+332.8, +785.6]) and M.ROSA group (+18.7 μM, p ≤ 0.0001, [+10.8, +26.5] and +463.7 nM, p ≤ 0.0001, [+314.3, +613.0]). Average peak value in NO metabolites concentration occurred earlier in M.CEVEDALE group vs M.ROSA group (NO3−, day 3 vs day 5, p = 0.007; NO2−, day 3 vs day 5, p = 0.019). In both groups, resting SpO2, HR and MAP values changed according to altitude levels.This study shows that exposure to hypobaric hypoxia affects nitric oxide metabolites, resulting in a significant increase in plasma NO3− and NO2− concentrations from sea level values. Interestingly, the higher the altitude reached, the longer the time taken to reach a peak in plasma concentrations of nitric oxide metabolites.

Affective dimensions of pain and region -specific involvement of nitric oxide in the development of empathic hyperalgesia

Empathy for pain depends on the ability to feel, recognize, comprehend and share painful emotional conditions of others. In this study, we investigated the role of NO in a rat model of empathic pain. Pain was socially transferred from the sibling demonstrator (SD) who experienced five formalin injection to the naïve sibling observer (SO) through observation. SO rats received L-NAME (a nonspecific NO synthase inhibitor) or L-arginine (a precursor of NO) prior to observing the SD. Nociception, and concentrations of NO metabolites (NOx) in the serum, left and right hippocampus, prefrontal cortex, and cerebellum were evaluated. Nociceptive responses were significantly increased in the pain-observing groups. NOx levels measured 24 h after the last pain observation using the Griess method, were indicative of NOx concentration decreases and increases in the left hippocampus and cerebellum, respectively. There was an increase in tissue concentration of NOx in cerebellum and prefrontal cortex in both pain and observer groups 7 days after the fifth formalin injection. Our results suggest that NO is involved in development of empathic hyperalgesia, and observation of sibling’s pain can change NO metabolites in different brain regions in observer rats.

Hypertension Editors' Picks Preeclampsia.

Hypertension Editors' Picks Preeclampsia.

Superimposed Preeclampsia Exacerbates Postpartum Renal Injury Despite Lack of Long-Term Blood Pressure Difference in the Dahl Salt-Sensitive Rat.

Preeclampsia results in increased susceptibility to hypertension and chronic kidney disease postpartum; however, the mechanisms responsible for disease progression in these women remain unknown. The purpose of this study was to test the hypothesis that 2 mechanisms contribute to the link between the maternal syndrome of preeclampsia and the increased postpartum risk of cardiovascular and renal disease: (1) increased T cells in the kidney and (2) a decreased NO:ET-1 (endothelin-1) ratio. Dahl S rats (a previously characterized model of preeclampsia superimposed on chronic hypertension) who experienced 2 pregnancies and virgin littermate controls were studied at 6 months of age. Mean arterial pressure was measured via telemetry, and renal injury was assessed through both histological analysis and measurement of urinary markers including nephrin, podocalyxin, and KIM-1 (kidney injury marker 1). Contributing mechanisms were assessed through flow cytometric analysis of renal T cells, quantification of plasma TNF-α (tumor necrosis factor-α) and IL-10 (interleukin-10), and quantification of urinary concentrations of NO metabolites and ET-1. Although prior pregnancy did not exacerbate the hypertension at 6 months, this group showed greater renal injury compared with virgin littermates. Flow cytometric analyses revealed an increase in renal T cells after pregnancy, and cytokine analysis revealed a systemic proinflammatory shift. Finally, the NO:ET-1 ratio was reduced. These results demonstrate that the link between the maternal syndrome of superimposed preeclampsia and postpartum risk of chronic kidney disease could involve both immune system activation and dysregulation of the NO:ET-1 balance.

Inhibition of the Expression of Inducible NO Synthase by Neuroactive Amino Acid Derivatives Phenibut and Glufimet In Vitro and Ex Vivo.

The effects of glufimet and phenibut (glutamic acid and GABA derivatives, respectively) on concentration of inducible NO synthase and cGMP in LPS-activated mouse peritoneal macrophages and on NO end products in their culture medium were examined in vitro and ex vivo. Addition of LPS into culture medium elevated concentration of NO metabolites in this medium and increased concentration of inducible NO synthase and cGMP in the lysates of peritoneal macrophages, whereas incubation of the cells with examined agents applied at concentration of 10-5 M diminished these indices. Similar results were obtained with intraperitoneal injection of LPS, glufimet, and phenibut. In culture medium containing peritoneal macrophages from the mice injected with LPS (100 μg/kg), the concentrations of inducible NO synthase and cGMP as well as the total concentration of nitrite and nitrate ions increased, whereas in culture medium with the cells from LPS-exposed mice treated with glufimet (28.7 mg/kg) and phenibut (50 mg/kg) these indices significantly decreased.

К ВОПРОСУ О ПАТОГЕНЕТИЧЕСКИХ МАРКЕРАХ ЭКОЛОГООБУСЛОВЛЕННЫХ БОЛЕЗНЕЙ ОРГАНОВ ДЫХАНИЯ

The aim of the research is to examine the relationship between the integral parameters of respiratory function, the values of LPO-AOD system and NO level at bronchopulmonary pathology in individuals living in different ecological areas of the city of Vladivostok. 206 patients living in different ecological conditions (healthy individuals, patients with respiratory disorders) were examined. Lung function and the state of LPO-AOD system were studied; the concentration of NO metabolites was assessed in blood serum. The nature and strength of the impact of environmental factors on respiratory function, the state of LPO-AOD, NO level were studied by the method based on correlation analysis. There was calculated power index (D) which was differentiated into power within the system (Ds) which in its turn reflects the in-system interrelationship tension (LPO-AOD, respiratory) and power between systems (Dm) characterizing the activity of interconnections and response to an external stimulus. Intra-system dependences typical for the unfavorable zone were viewed in relation to the favorable zone. It was found out that in ecologically unfavorable regions in individuals with different bronchopulmonary pathologies the value of Ds increases. This indicates that the pathogenic influence of environmental factors increases. In healthy people living in ecologically unfavourable area physiological adaptive-compensatory reaction of the body was revealed, which was proved by high power interconnections (Dm). In the patients with chronic bronchitis there was maintained an adequate level of functioning of the body systems studied. In patients with COPD living in an unfavourable zone there were found strong links between the indicators of the system of LPO-AOD and of NO, and in patients with bronchial asthma - supplementary relationship between lung function and NO. At the same time pathologic changes in the system of LPO-AOD and NO depend on the general pollution, metal and gas components contained in the air. Thus, the people with respiratory diseases being in environmentally unfavorable conditions have the most negative influence. The analysis of the activity of relationships proved that violations of interaction of LPO-AOD systems and NO in ecologically unfavorable regions may contribute to the occurrence and progression of bronchopulmonary diseases.

Endothelium protecting properties of taurin in chronic heart failure with type 2 diabetes

High prevalence of chronic heart failure (CHF) and type 2 diabetes (DM2), poor prognosis and low life quality determine the aim for optimum treatment strategy invention. Cornerstone of the treatment in this category of patients is correction of endothelial dysfunction and metabolism disorders that underlie development and progression of CHF and DM2: lipid- and glucose toxicity, insulin resistance (IR). Aim. To study the effects of taurin treatment as part of combination therapy for CHF with DM2, taking its influence on endothelial dysfunction. Material and methods. Totally, 60 patients included, after myocardial infarction (MI) lasting 6-12 months, with CHF I-III functional class and comorbid DM2. They were selected to 2 groups: 1st (controls) — patients receiving CHF treatment in postinfarction period and oral glucose lowering drugs, and 2nd (experimental) — patients also taking taurin 500 mg b.i.d. together with CHF and DM2 treatment. Assessment included 6-minute walking test, measurement of brain natriuretic peptide (NT-proBNP) in blood, echocardiography, vascular components of endothelium functioning, plasmatic factors of endothelial function (NO metabolites concentration and endotheline-1 in serum), glucose level, insulin with IR-index, glycosilated hemoglobine, total cholesterol, low density and high density lipoproteides, triglycerides. Results. It is found, that taurin shows endothelium protecting properties when used as part of combination therapy for CHF and DM2. These properties were noted on microcirculatory (significant in spastic pattern of disorder) level and in elastic arteries. While taking taurin, there was statistically significant increase of NO level in blood and decrease of endotheline-1. Conclusion. Positive endothelium protecting properties of taurin as part of combination therapy of CHF with DM2 were followed by significant decrease of CHF severity by NT-proBNP levels dynamics, and significant hypolipidemic effect, decrease of IR.

Studying the functional condition of rat epididymis mitochondria at nitric oxide (II) synthesis change

Aim. To study the levels of nitric oxide (II) metabolites, lactate, endogenic carnitine and mitochondrial oxidoreductase activity in epididymis tissue at nitric oxide low synthesis and, based on the obtained data, to assess the functional condition of rat epididymis mitochondria.&#x0D; Methods. 16 Wistar rats were allocated to two equal groups: The first group was administered L-NG-nitroarginine methyl ester (L-NAME), which is non-selective NO-synthase inhibitor, at a dose of 25 mg/kg for 7 days. The second group (the control group) got 0.9% sodium chloride solution administered as intraperitoneal injection for 7 days. Homogenate was obtained from epididymis tissue (head and tail), and mitochondria were isolated from it by differential centrifugation. Activities of mitochondrial enzymes (lactate dehydrogenase, succinate dehydrogenase and superoxide dismutase) were measured, as well as concentrations of NO metabolites, lactate, total protein and endogenous carnitine.&#x0D; Results. Activity of succinate dehydrogenase was significantly decreased by 55 and 68%, lactate dehydrogenase activity - by 78 and 92%, superoxide dismutase - by 16 and 43% in the mitochondria of epididymis head and tail tissue, respectively in the group receiving 25 mg/kg of L-NAME, compared to the control group. The concentrations of NO metabolites decreased by 18 and 30%, lactate levels increased by 43 and 35%, the share of bounded carnitine decreased by 25% in epididymis tail. Changes of carnitine concentrations in epididymis head were non-significant.&#x0D; Conclusion. In L-NAME-induced deficiency of NO in epididymis tissues mitochondria, statistically significant decrease in the activity of mitochondrial oxidoreductases and lactate accumulation was noticed, indicating the development of secondary mitochondrial dysfunction.

Formation of nitric oxide metabolites during growth of transplanted tumors with different metastatic potential

The dynamics of the endogenous production of NO metabolites, nitrites, nitrates, and volatile nitrosamines, has been investigated in the body, a tumor tissue, and peritoneal macrophages of mice F1 (C57Bl × CBA), Balb/c and BDF with subcutaneously transplanted tumors: Ehrlich carcinoma (EC) and Lewis metastatic lung carcinoma (LC). It has been shown that during the first three weeks, growth of EC is accompanied by a statistically significant increase in the total concentration of NO metabolites (NOx; nitrites + nitrates) up to levels (7.3 ± 3.49) × 10−6−(7.8 ± 2.57) × 10−5 mol/kg in the tumor tissue and a sharp increase in NOx excretion with urine. At the same time, in the LC tumor tissue the maximal level of NOx (3.6 ± 0.46) × 10−5 mol/kg was registered on day 7, and later it decreased demonstrating negative correlation with the tumor mass. At the stage of intensive LC growth (14, 21 days) there was significant inhibition of nitrite secretion by peritoneal macrophages. In all the controlled time-intervals the EC tumor tissue contained carcinogenic N-nitrosodimethylamine and N-nitrosodiethylamine; however, their concentrations significantly varied. Thus, the ability of the tumor tissue to produce NO metabolites was more pronounced in EC than in LC and depended on the time parameters of tumor growth.

Возможности коррекции дисфункции эндотелия на фоне комбинированной антигипертензивной терапии у больных артериальной гипертонией с сахарным диабетом 2-го типа

To evaluate the impact of a 12-week combined antihypertensive therapy with enalapril + indapamide on endothelial dysfunction in patients with arterial hypertension (AH) and diabetes mellitus (DM) type 2.30 patients with AH stage II-III and DM type 2 age from 40 to 65 years were included into research. The combined antihypertensive therapy with enalapril 28.6 ± 1.9 + indapamide 2.5 ± 0 mg/day was assigned for 12 weeks. We studied endothelial function by determining the concentration of NO metabolites and endothelin-1 in serum and urine, the results of occlusion test.After 12-week therapy, 100% of the patients achieved BP goals. There was no impairment of carbohydrate metabolism. Endothelial function was improved in hypertensive patients with T2DM: there were increases in both serum and urinary NO production (by 381 and 48.2%, respectively) and decreases in urinary endothelin-1 secretion (by 56.3%). The number of patients with normal microcirculation increased from 13.3 to 53.3% (p < 0.001) by reducing the number of patients with abnormal (hyperemic and stagnant-stasic) types of microcirculation.Twelve-week treatment with the combined antihypertensive medication. The combined antihypertensive therapy with enalapril + indapamide is highly effective and safe for recovering endothelial function in hypertensive patients with T2DM.

Transforming Growth Factor-β Regulates Endothelial Function During High Salt Intake in Rats

Previous studies have demonstrated that an increase in dietary NaCl (salt) intake stimulated endothelial cells to produce transforming growth factor-β (TGF-β). The intent of the present study was to determine the functional significance of increased TGF-β on endothelial cell function. Young Sprague-Dawley rats were fed diets containing 0.3 or 8.0% NaCl for 2 days before treatment with a specific inhibitor of the TGF-β receptor I/activin receptor-like kinase 5 kinase, or vehicle for another 2 days. At day 4 of study, endothelial phosphorylated Smad2 (S465/467) increased and phosphatase and tensin homologue deleted on chromosome 10 (PTEN) levels decreased in the high-salt–treated rats. In addition, phosphorylated Akt (S473) and phosphorylation of the endothelial isoform of NO synthase (NOS3) at S1177 increased. Treatment with the TGF-β receptor I/activin receptor-like kinase 5 inhibitor reduced Smad2 phosphorylation to levels observed in rats on the low-salt diet and prevented the downstream signaling events induced by the high-salt diet. In human umbilical vein endothelial cells, reduction in PTEN levels increased phosphorylated Akt and NOS3. Treatment of macrovascular endothelial cells with TGF-β1 increased phosphorylated NOS3 and the concentration of NO metabolites in the medium but had no effect on either of these variables in cells pretreated with small interfering RNA directed against PTEN. Thus, during high salt intake, an increase in TGF-β directly promoted a reduction in endothelial PTEN levels, which in turn regulated Akt activation and NOS3 phosphorylation. This effect closes a feedback loop that potentially mitigates the effect of TGF-β on the vasculature.

Role of Endothelial Dysfunction and Lymphocyte-Platelet Adhesion in the Pathogenesis of Bile Peritonitis

Bile peritonitis is associated with endotoxemia, endothelial dysfunction, and increased level of pro-inflammatory cytokines. Under these conditions, serum concentration of NO metabolites (nitrate/nitrite ratio) and NO production by platelets significantly increase in animals with bile peritonitis, which reflects the development of inflammatory process and its antithrombotic activity, respectively. At the same time, platelet adhesion to lymphocytes increased in animals with bile peritonitis. The observed effect was confirmed by a direct correlation between the adhesion activity of lymphocytes to platelets and the content of desquamated endotheliocytes. This phenomenon played a crucial role in the development of protective and reparative processes in the damaged surface of vessel wall.

Antihypertensive and antioxidant potential of vanillic acid, a phenolic compound in l-NAME-induced hypertensive rats: A dose-dependence study

We investigated the antihypertensive and antioxidant potential of vanillic acid (VA) in Nω-Nitro-l-arginine methyl ester hydrochloride (l-NAME) – treated adult male albino Wistar rats. Treatment of rats with l-NAME (40 mg/kg Bw for 30 days) caused a sustained increase in systolic- (SBP) and diastolic blood pressure (DBP) and significantly decreased the concentration of nitrite/nitrate (NOx) in plasma as compared with that in the control. Rats treated with VA restored SBP and DBP to normal level and preserve the plasma NO metabolites concentration. Moreover, VA reduced lipid peroxidation products (thiobarbituric acid reactive substances, lipid hydroperoxides, conjugated dienes) and significantly restored enzymatic antioxidants (superoxide dismutase, catalase, and glutathione peroxidase), non-enzymatic antioxidants (vitamin C, vitamin E, and reduced glutathione) in the plasma. To assess the toxicity if any of VA treatment, hepatic and renal function markers were measured. Our results showed that the effect at a dose of 50 mg/kg Bw of VA was more pronounced than that of the other two doses, 25 and 100 mg/kg Bw. These results were supported by histopathology studies. We conclude that VA possesses an antihypertensive and antioxidant activity in l-NAME-induced hypertensive rats.

Urinary Nitrate Might Be an Early Biomarker for Pediatric Acute Kidney Injury in the Emergency Department

NO is involved in normal kidney function and perturbed in acute kidney injury (AKI). We hypothesized that urinary concentration of NO metabolites, nitrite, and nitrate would be lower in children with early AKI presenting to the emergency department (ED), when serum creatinine (SCr) was uninformative. Patients up to 19 y were recruited if they had a urinalysis and SCr obtained for routine care. Primary outcome, AKI, was defined by pediatric Risk, Injury, Failure, Loss of function, End-stage renal disease (pRIFLE) criteria. Urinary nitrite and nitrate were determined by HPLC. A total of 252 patients were enrolled, the majority (93%) of whom were without AKI. Although 18 (7%) had AKI by pRIFLE, 50% may not have had it identified by the SCr value alone at the time of visit. Median urinary nitrate was lower for injury versus risk (p = 0.03); this difference remained significant when the injury group was compared against the combined risk and no AKI groups (p = 0.01). Urinary nitrite was not significantly different between groups. Thus, low urinary nitrate is associated with AKI in the pediatric ED even when SCr is normal. Predictive potential of this putative urinary biomarker for AKI needs further evaluation in sicker patients.

Nitric oxide metabolites in goldfish under normoxic and hypoxic conditions

Nitric oxide (NO), produced by nitric oxide synthases (NOS enzymes), regulates multiple physiological functions in animals. NO exerts its effects by binding to iron (Fe) of heme groups (exemplified by the activation of soluble guanylyl cyclase) and by S-nitrosylation of proteins - and it is metabolized to nitrite and nitrate. Nitrite is used as a marker for NOS activity but it is also a NO donor that can be activated by various cellular proteins under hypoxic conditions. Here, we report the first systematic study of NO metabolites (nitrite, nitrate, S-nitroso, N-nitroso and Fe-nitrosyl compounds) in multiple tissues of a non-mammalian vertebrate (goldfish) under normoxic and hypoxic conditions. NO metabolites were measured in blood (plasma and red cells) and heart, brain, gill, liver, kidney and skeletal muscle, using highly sensitive reductive chemiluminescence. The severity of the chosen hypoxia levels was assessed from metabolic and respiratory variables. In normoxic goldfish, the concentrations of NO metabolites in plasma and tissues were comparable with values reported in mammals, indicative of similar NOS activity. Exposure to hypoxia [at P(O₂) (partial pressure of O₂) values close to and below the critical P(O₂)] for two days caused large decreases in plasma nitrite and nitrate, which suggests reduced NOS activity and increased nitrite/nitrate utilization or loss. Tissue NO metabolites were largely maintained at their tissue-specific values under hypoxia, pointing at nitrite transfer from extracellular to intracellular compartments and cellular NO generation from nitrite. The data highlights the preference of goldfish to defend intracellular NO homeostasis during hypoxia.

Effect of aqueous extracts of Ecballium elaterium rich, in the rabbit model of rhinosinusitis

This study was designated to investigate anti-inflammatory effect of aqueous extract of Ecballium elaterium, which is topically applied for treatment of rhinosinusitis as a traditional folk medicine in Turkey. Therapeutic potential of E. elaterium as an anti-inflammatory agent was examined by measurement of NO* metabolites in a rabbit model of rhinosinusitis. The results showed that both activity of NOS enzyme and concentration of NO* metabolites were significantly reduced by topical administration of E. elaterium extract in therapy group as compared to the control. Thus, the data suggest E. elaterium extract may have the potential to be used as anti-inflammation agent, and can be used in the treatment of rhinosinusitis diseases.