正常高值血压患者血浆血管活性因子和抗氧化酶的变化及其意义

目的正常高值血压具有较高的发展成为高血压的危险性。本研究的目的是观察正常高值血压患者血浆中血管活性因子和抗氧化酶的变化,以探讨其在高血压治疗和预防方面的意义。方法根据JNC-7诊断标准筛选病例并分为三组：正常血压组（NT组）为74例正常血压健康人,男性38例,女性36例,平均年龄（47．15±7．77）岁;正常高值血压组（PH组）为51例正常高值血压患者,男性29例,女性22例,平均年龄（47．82±5．16）岁;高血压组（EH组）为71例原发性高血压患者,男性37例,女性34例,平均年龄（48．25±7．97）岁。抽取静脉血,离心后分别采用放免法和酶联免疫法测定血中的血管紧张素Ⅱ（AngⅡ）、内皮素（ET）、血管加压素（AVP）、降钙素基因相关肽（CGRP）、一氧化氮合成酶（NOS）、超氧化物岐化酶（SOD）和谷胱甘肽过氧化物酶（GPX）等含量。结果与NT组相比,EH组和PH组血中甘油三酯、总胆固醇和低密度脂蛋白胆固醇水平明显升高（P〈0．05）;高密度脂蛋白胆固醇在PH组中降低,EH组明显降低（P〈0．05）;AngⅡ、AVP和ET在EH组和PH组均增高（P〈0．05）;CGRP在PH组和EH组均下降（P〈0．05;P〉0．05）;NOS在三组之间无明显的差异;SOD在PH和EH组明显下降（P〈0．05;P〈0．01）而GPX明显增高（P〈0．05;P〈0．01）。结论PH患者血中脂类物质、血管活性物质、抗氧化酶出现了异常变化,这会增加患高血压的可能性。为尽可能减少和防止其进展为高血压,应该对PH患者进行相应的治疗和控制。     

Antioxidant enzyme activities in healthy Chinese adults: influence of age, gender and smoking

OBJECTIVE: Specific antioxidant enzymes play a vital role in regulating and maintaining oxidant species. The aim of this study was to determine these antioxidant enzyme activities (i.e. catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx)) in erythrocytes from a group of healthy Chinese subjects and to study the influence of age, gender and smoking habits on the enzyme activities. METHODOLOGY: Chinese healthy subjects (n = 276) were grouped according to their age range, gender differences and smoking habits. Antioxidant enzyme activities were measured spectrophotometrically using standard kinetic methods. RESULTS: There was a significant decrease in erythrocyte GPx activity in ever-smokers compared with non-smokers (47.10 +/- 1.33 mU/g haemoglobin (Hb) vs. 51.41 +/- 1.64 mU/g Hb, P < 0.05). Age-related significant increases in erythrocyte CAT and SOD activities were found in non-smokers but not in ever-smokers. There was no age-related difference in erythrocyte GPx activity in either non-smokers or ever-smokers. Among those >60 years old, erythrocyte CAT and GPx activities were significantly lower in ever-smokers than in non-smokers (29.70 +/- 3.07 mU/g Hb vs. 41.63 +/- 4.92 mU/g Hb (P < 0.05), and 47.55 +/- 2.00 mU/g Hb vs. 55.30 +/- 3.60 mU/g Hb (P < 0.05), respectively). It was also found that females had higher erythrocyte GPx activity than males but this difference did not reach significance in non-smokers. CONCLUSION: From the results of this study, it is concluded that oxidative stress seems to be present in elderly ever-smokers among the Chinese population.     

Pharmacological concentrations of ascorbic acid are required for the beneficial effect on endothelial vasomotor function in hypertension

Increased production of superoxide anion may contribute to impaired bioactivity of endothelium-derived nitric oxide in hypertension. Ascorbic acid is capable of scavenging superoxide anion; however, experimental studies have shown that high physiological concentrations (>1 mmol/L) of ascorbic acid are required to prevent superoxide-mediated vascular dysfunction. To seek kinetic evidence that superoxide anion contributes to endothelial vasomotor dysfunction in human hypertension, we examined the effects of 2.4 or 24 mg/min ascorbic acid intra-arterial infusions on forearm blood flow responses to methacholine or sodium nitroprusside in 30 patients with hypertension and 22 age-matched controls. Endothelium-dependent vasodilation to methacholine was significantly impaired in the hypertensive patients, with a response to the highest dose of methacholine (10 microg/min) of 12.3+/-6.7 compared with 16.1+/-5.8 mL. min(-1). dL tissue(-1) in the controls (P<0.001). The response to sodium nitroprusside was equivalent in the 2 groups. Ascorbic acid at 24 mg/min significantly improved the forearm blood flow response to methacholine in hypertensive patients with a peak response of 16.1+/-7.1 mL. min(-1). dL tissue(-1) (P=0.001). This dose produced a cephalic vein ascorbic acid concentration of 3.2+/-1. 4 mmol/L. In contrast, ascorbic acid at 2.4 mg/min had no effect on the methacholine response. Ascorbic acid at both doses had no effect on the vasodilator response to sodium nitroprusside in hypertensive patients or the methacholine response in the controls. These results agree with the predicted kinetics for superoxide anion-mediated impairment of endothelium-derived nitric oxide action. Thus, superoxide anion may contribute to impaired endothelium-dependent vasodilation in patients with hypertension.     

Lipid peroxidation and antioxidant enzyme levels in type 2 diabetics with microvascular complications

Serum levels of total cholesterol, triglycerides, lipoproteins, lipid peroxides (TBARS) and erythrocyte antioxidant enzyme activities were measured in 105 non insulin dependent diabetic patients, among whom 38 had microvascular complications (MVC) of diabetes. All the diabetic patients had higher concentrations of glycated hemoglobin (HbA1) compared to controls (10.51 +/- 2.42% vs 6.31 +/- 0.85% P <0.001). Significant increase of serum triglycerides (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and very low density lipoprotein cholesterol (VLDL-C) and a significant decrease of high density lipoprotein cholesterol (HDL-C) were observed in the diabetic patients compared to controls (TG: 2.31 +/- 0.9 mmol/l vs 1.53 +/- 0.48 mmol/l P <0. 001; TC: 5.94 +/- 1.4 mmol/l vs 4.3 +/- 0.85 mmol/l P <0.001; LDL-C: 3.96 +/- 1.33 mmol/l vs 2.39 +/- 0.8 mmol/l P <0.001; VLDL-C: 0.46 +/- 0.2 mmol/l vs 0.3 +/- 0.09 mmol/l P <0.001; HDL-C: 0.81 +/- 0.24 mmol/l vs 1.04 +/- 0.18 mmol/l P <0.001). Significantly increased levels of serum TBARS were observed in diabetic patients compared to those in controls (TBARS: 6.7 +/- 1.5 mmol/l vs 5.14 +/- 0.61 mmol/l P <0.001). Erythrocyte catalase (CAT) activity was increased and Glutathione peroxidase (GPx) activity was decreased in diabetic patients compared to controls, but no significant change in Superoxide dismutase (SOD) activity was observed in diabetic patients (CAT: 104.94 +/- 37.1 KU/g Hb vs 85.8 +/- 23.6 KU/g Hb, P <0.01; GPx: 30 +/- 9.7 U/g Hb/min vs 40.84 +/- 12.3 U/g Hb/min, P <0. 001; SOD: 2.4 +/- 1.2 U/mg Hb/min vs 2.55 +/- 0.84 U/mg Hb/min, P=NS). In comparison with the diabetic group without MVC, the diabetic group with MVC had decreased GPx and SOD activities, while no difference was observed between these two groups regarding CAT activity (GPx: 25.32 +/- 8.4 U/g Hb/min vs 34.5 +/- 8.8 U/g Hb/min, P <0.001; SOD: 1.83 +/- 0.53 U/mg Hb/min vs 2.84 +/- 1.4 U/mg Hb/min, P<0.001; CAT: 106.3 +/- 39.9 KU/g Hb vs 103 +/- 34.9 KU/g Hb, P =NS). TBARS concentrations were significantly increased in the group with MVC compared to the group without these complications, indicating a positive relationship between TBARS and MVC of diabetes (7.05 +/- 1.23 mmol/l vs 6.3 +/- 1.02 mmol/l, P <0.001). Serum triglycerides, LDL and VLDL cholesterol concentration were significantly higher in diabetics with MVC than in diabetics without the complications (TG: 2.7 +/- 0.98 mmol/l vs 2.13 +/- 0.82 mmol/l, P<0.01; LDL - C: 4.45 +/- 1.3 mmol/l vs 3.67 +/- 1.3 mmol/l, P <0. 02; VLDL-C: 0.53 +/- 0.19 mmol/l vs 0.43 +/- 0.16 mmol/l, P <0.01), and the serum levels of TC in the group with MVC showed a positive correlation with their lipid peroxide levels (r =0.368, P <0.001). The increase in TBARS and the decreased GPx and SOD activities in diabetics with MVC in this study indicate that these factors may contribute to the occurrence of micro vascular complications in NIDDM patients.     

吸烟对脂质过氧化抗氧化系统及α1-抗胰蛋白酶的影响

通过检测３１３名吸烟血中自由基水平及α１－抗胰蛋白酶的变化。探讨氧自由基在吸烟致病中的作用。方法 试验分为非吸烟组１８９名，轻度吸烟组６８名，中度吸烟组１８０名；重度吸烟组６５名，采用硫代巴比妥酸法，放射免疫法，５‘５二硫代安息香酸直接法，Ｅｌｌｍａｎ法，酶标法分别检测脂质过氧化物，超氧化物歧化酶，谷胱甘肽过氧化物酶，谷胱甘肽及α１－ＡＴ。     

Antioxidant enzymes in hypertensive and hypertriglyceridemic rats: effect of gender

In a model of hypertensive and hypertriglyceridemic rats (HTG), in which oxidative stress is increased, the influence of gender upon activities of catalase (CAT), glutathione peroxidase (GPX), and superoxide dismutase (SOD) was investigated. Statistically significant differences between antioxidant enzyme activities and treatment with relation to gender were analyzed. Weanling Wistar rats were given normal rat chow and either tap water for control group or 30% sucrose solution for HTG group, for 5-6 months. At the end of the experimental period, blood pressure was significantly higher in both male and female HTG groups, but males showed higher values than females. Serum, heart, kidney, and liver were obtained to determine antioxidant enzyme activities. Activities of CAT and GPX tended to be higher in male animals. A larger number of significant changes in enzyme activities associated with gender appears in HTG than in controls, which indicates the harmful effect of the treatment.     

Red cell superoxide dismutase and sickle cell anemia symptom severity

Patients with sickle cell anemia vary in the severity of their symptoms but the basis of this variability is unknown. We have tested the hypothesis that this variability is related to differences in the activity of the antioxidant superoxide dismutase (SOD). The amount of superoxide dismutase I (SOD) enzyme activity in red cells of patients with different degrees of symptom severity and healthy black and white controls was measured and correlated with symptom severity in SCA patients. Blacks with normal (AA) hemoglobin had significantly (p less than .001) more SOD activity (1.82 U/mg Hb) than white controls (1.44 U/mg Hb). Patients with moderate or severe symptoms had less SOD activity (1.16 and 0.95 U/mg Hb, respectively) than control blacks or SCA patients with mild symptoms (1.62 U/mg Hb). The correlation of SOD activity and symptom severity was not a function of age or sex and was unrelated to reticulocyte count or fetal hemoglobin level.     

Irbesartan lowers superoxide levels and increases nitric oxide bioavailability in blood vessels from spontaneously hypertensive stroke-prone rats

OBJECTIVE : To determine the effects of the angiotensin II receptor antagonist irbesartan, the calcium-channel blocker amlodipine, and hydrochlorothiazide/hydralazine on superoxide, NAD(P)H oxidase and nitric oxide bioavailability in spontaneously hypertensive stroke-prone rats (SHRSP). METHODS : Drugs or vehicle were administered for 8 weeks to SHRSP and blood pressure was measured weekly by tail-cuff plethysmography. After 8 weeks, superoxide levels in carotid arteries and aortas were measured by lucigenin chemiluminescence and p22phox expression quantified by immunohistochemistry. In vitro the effects of exposure to drugs and vehicle for 30 min and 4 h on superoxide levels and nitric oxide bioavailability were examined. The latter was expressed as the increase in contractile responses of carotid arteries to phenylephrine in the presence of the nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester(l-NAME). RESULTS : In vivo irbesartan, amlodipine and hydrochlorothiazide/hydralazine produced similar falls in blood pressure, from 162 +/- 4 to 125 +/- 5, 132 +/- 4 and 131 +/- 6 mmHg, respectively, but irbesartan caused a greater reduction in superoxide and p22phox; superoxide levels in carotid arteries being 3.1 +/- 0.3, 1.1 +/- 0.2, 1.9 +/- 0.3 and 2.0 +/- 0.3 nmoles/mg per min, respectively. In vitro 4 h exposure to irbesartan decreased superoxide levels in the aorta from 2.08 +/- 0.68 to 1.48 +/- 0.62 nmoles/mg per min and increased nitric oxide bioavailability in carotid arteries. Neither 30 min incubation with irbesartan nor 4 h with amlodipine or hydrochlorothiazide/hydralazine altered superoxide levels. CONCLUSIONS : These studies support the hypothesis that AT1 receptor blockade has beneficial effects on superoxide production and nitric oxide bioavailability above that of other classes of antihypertensive agents. Reduced expression of components of the NAD(P)H oxidase may contribute to these effects.     

Byproducts of oxidative protein damage and antioxidant enzyme activities in plasma of patients with different degrees of essential hypertension

Despite evidence that essential hypertension (EH) is a state of increased oxidative stress, the data on oxidative protein modifications is lacking. Besides, the role of extracellular antioxidant enzymes in EH has not been systematically studied. Study was performed in 45 subjects with EH and 25 normotensive controls. Patients were divided into three groups according to the 2003 ESH/ESC guidelines (grade 1-3). Plasma protein reactive carbonyl derivatives (RCD) and SH-groups (as byproducts of oxidative protein damage) as well as antioxidant enzyme activities superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase were studied spectrophotometrically and correlated with blood pressure (BP). RCD levels were increased in EH patients compared to controls and correlated significantly with both systolic blood pressure (SBP) (r = 0.495, P<0.01) and diastolic blood pressure (DBP) (r = 0.534, P<0.01). Plasma SH-groups content was significantly lower in all patients with EH, with no correlation with BP. SOD and catalase activity in patients with grade 1 EH were similar to that of controls. Patients with grade 2 and 3 of EH had lower SOD and catalase activity. However, significant correlation with SBP and DBP was observed for catalase only (r = -0.331; P<0.05 and r = -0.365; P<0.05, respectively). EH patients exhibited higher plasma GPX activity compared to those in controls, and it correlated with SBP (r = 0.328; P<0.05). The results presented show that increased oxidative protein damage is present in all grades of EH. In mild hypertension extracellular antioxidant enzyme activities are not decreased, suggesting they are probably not critical in early EH, but could be important in moderate to severe EH.     

Impairment of erythrocyte anti-oxidant defense mechanisms in hypoxemic patients

Defense mechanisms against lipid peroxidation were studied in erythrocytes from hypoxemic patients. The levels of lipid peroxides in patients erythrocytes were higher than those of control subjects (15.3 +/- 10.9 vs 7.5 +/- 3.0, p less than 0.05). The levels of reduced glutathione (GSH) decreased in erythrocytes from the patients (426 +/- 108 vs 756 +/- 201, p less than 0.01). Activities of glutathione peroxidase (GPX) and superoxide dismutase (SOD) were lower than those of control subjects (GPX; 27.6 +/- 7.1 vs 35.1 +/- 3.8, SOD; 76.6 +/- 42.9 vs 125.7 +/- 40.1, p less than 0.01). Positive correlations were observed between the levels of arterial oxygen pressures (PaO2) and the GSH concentrations, the activities of GPX and SOD, respectively. These data suggest that decreased anti-oxidant activity enhances lipid peroxidation in erythrocytes from hypoxemic patients.     

Erythrocyte antioxidant enzymes and blood pressure in relation to overweight and obese Thai in Bangkok

The specific activities of antioxidant enzymes, [eg superoxide dismutases (SOD), glutathione peroxidase (GPX) and catalase (CAT)], anthropometric measurements, including waist/hip ratio of 48 male and 167 female overweight persons (body mass index (BMI) > or = 25.0 kg/m2) compared with a 26 male and 80 female control group (BMI = 18.5-24.9 kg/m2) of Thai volunteers who attended the Out-patient Department, General Practice Section, Rajvithi Hospital, Bangkok, for a physical check-up during March-October, 1998, were investigated. There was a slightly significant difference between the median age of the sexes. The medians of height, weight, and waist/hip ratio in males were significantly higher than those in female overweight and obese subjects. The median of arm circumference (AC), mid arm muscle circumference (MAMC) in males was significantly higher than those in female overweight and obese subjects (p < 0.05). The prevalences of hypertension based on systolic and diastolic blood pressure of > or = 160/> or = 95 mmHg, were 8.3% and 37.5% for males and 5.4% and 18.6% for females, respectively. There was no significant difference between the median of antioxidant enzymes (SOD, GPX and CAT) between the sexes. No significant differences in the antioxidant enzymes in male overweight/obese persons and normal controls were presented, whereas antioxidant enzymes in female overweight/obese persons were statistically lower than in control females (p < 0.05). A significantly higher SOD, GPX, and CAT status was observed in normal subjects compared with overweight/obese subjects (p < 0.01). A higher prevalence of SOD < or = 2,866 U/gHb, GPX (< or = 15.96 U/gHb in females was found, compared with males. A high percentage of lower catalase (CAT < or = 19.2x10(4) IU/gHb) was found in both sexes (64.5% in males and 64.5% in females). In obese subjects (BMI > or = 30.0 kg/m2), there were significantly positive relationships between systolic and diastolic blood pressure, systolic blood pressure and waist/hip ratio, and SOD could be related to weight, BMI as well as GPX and CAT, whereas the opposite result was observed for age and SOD.     

The effects of L-carnitine treatment on left ventricular function and erythrocyte superoxide dismutase activity in patients with ischemic cardiomyopathy

We studied the effects of L-carnitine on left ventricular systolic function and the erythrocyte superoxide dismutase activity in 51 patients with ischemic cardiomyopathy. They all previously were under the treatment of angiotensin-converting enzyme inhibitor, digitalis and diuretics. Patients were randomized into two groups. In group I (n=31), 2 g/day L-carnitine was added to therapy. L-Carnitine was not given to the other 20 patients (Group II). In group I (mean age 64.3+/-7.8 years), 27 of the patients were men, and four were women. In group II (mean age 66.2+/-8.7 years), 17 of the patients were men, and three were women. Twenty age-matched healthy subjects (mean age: 60.1+/-5.3 years) constituted the control group. In each group, left ventricular ejection fraction (LVEF) by echocardiography and red cell superoxide dismutase activity by spectrophotometric method were measured initially and after 1 month of randomisation. Compared with normal healthy subjects (n=20), patients (n=51) had significantly higher red cell SOD activity (5633+/-1225 vs. 3202+/-373 U/g Hb, P<0.001). At the end of 1 month of L-carnitine therapy, red cell SOD activity showed an increase in group I (5918+/-1448 to 7218+/-1917 U/g Hb, P<0.05). In group II, red cell SOD activity showed no significant change after 1 month of randomisation (5190+/-545 to 5234+/-487 U/g Hb, P=0. 256). One month after randomisation there was a significant increase in LVEF in both groups I and II (37.8-42.3%, P<0.001 in group I; 41. 5-43.8%, P<0.001 in group II). The improvement in LVEF was more significant in the L-carnitine group (4.5% vs. 2.3%, P<0.01). We conclude that, as a sign of increased free radical production, superoxide dismutase activity was further increased in patients with L-carnitine treatment. L-Carnitine treatment in combination with other traditional pharmacological therapy might have an additive effect for the improvement of left ventricular function in ischemic cardiomyopathy.     

Dysregulation of hepatic superoxide dismutase, catalase and glutathione peroxidase in diabetes: response to insulin and antioxidant therapies

Recent evidence suggests that impaired antioxidant status is involved in oxidative stress associated with diabetes. The main antioxidant enzymes include superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX). The aim of the present investigation was to evaluate the activities and protein expression of these antioxidant enzymes in streptozotocin-induced diabetes. Furthermore, the effects of insulin and antioxidant therapy alone and in combination were studied. Male Sprague-Dawley rats were rendered diabetic by streptozotocin administration and randomly assigned to untreated, insulin-treated, antioxidant (vitamin E and C)-treated and insulin plus antioxidant-treated groups. Normal rats fed either a regular diet or the antioxidant (vitamin E and C)-rich diet served as controls. The animals were observed for 4 weeks. Diabetic animals showed marked weight loss, decreased activities of Cu Zn SOD and CAT and normal GPX activity. Additionally, the expression of all antioxidant enzyme proteins was decreased in the diabetic rats compared to the untreated controls. Insulin therapy prevented weight loss and normalized the activities and protein expression of all antioxidant enzymes. Antioxidant therapy in the diabetic rats normalized Cu Zn SOD and GPX protein expression. Combined therapy with insulin and antioxidants normalized all measured antioxidant enzyme protein expression and activities. Thus diabetes-associated reductions in antioxidant enzymes can be ameliorated by insulin and/or antioxidant therapy.     

Selenium levels and glutathione peroxidase activities in patients with acute myocardial infarction

OBJECTIVE: Selenium (Se) is part of the enzyme glutathione peroxidase (GSH-Px) that plays an important role in the antioxidant defence of the body, including the myocardium, against the deleterious actions of free radicals and lipid peroxides. In order to evaluate the Se status and the GSH-Px activity in ischaemic heart disease, plasma, erythrocyte and urinary Se concentrations together with plasma and erythrocyte GSH-Px activities were determined in 27 patients diagnosed as acute myocardial infarction (AMI). The control group consisted of 24 age-matched healthy individuals. METHODS AND RESULTS: Fasting blood and urine samples were collected within 24 hours after the onset of chest pain. Mean plasma, erythrocyte and urine Se concentrations were significantly lower in the patient groups (63.7 +/- 12 micrograms/l, 0.48 +/- 0.04 microgram/g Hb and 49.6 +/- 27.7 micrograms/g creatinine, respectively), compared to controls (82.2 +/- 14.6 micrograms/l, 0.51 +/- 0.03 microgram/g Hb and 93.4 +/- 62.6 micrograms/g creatinine, p < 0.001, p < 0.02 and p < 0.003, respectively). No statistically significant difference was found between mean plasma GSH-Px activity in patients (0.36 +/- 0.1 U/ml) and controls (0.35 +/- 0.09 U/ml), whereas erythrocyte GSH-Px activity was higher in patients (48.1 +/- 10.2 U/g Hb) than in the controls (35.3 +/- 9.1 U/g Hb, p < 0.001). CONCLUSION: Our findings confirm the previous studies and demonstrate that patients suffering from AMI exhibit lower plasma, erythrocyte and urinary Se than the controls. Since the erythrocyte Se level represents a measure of the Se status over a period of several weeks due to its long biological half-life, low Se levels observed in the patient group might have been present before the acute event, thereby suggesting an aetiologic relevance. The presence of increased erythrocyte GSH-Px activity in these patients may be interpreted as an antioxidant defence against the chronic oxidant stress present before the AMI, presumably due to the process of coronary atherosclerosis.     

Oxidative stress in juvenile essential hypertension

OBJECTIVE: Oxidative stress, an antioxidant/pro-oxidant imbalance, in patients with juvenile essential hypertension was measured via several biochemical parameters. As the blood pressure is associated with the body mass index (BMI), results were compared with those on BMI-matched controls. DESIGN AND SETTING: A prospective observational study at a university teaching hospital. PATIENTS: Children and adolescents with essential hypertension (mean standard deviation: age 14.4 +/- 3.1 years, BMI 25.0 +/- 6.9 kg/m(2), n = 52) before any treatment, and controls with a similar BMI distribution (age 14.3 +/- 4.3 years, BMI 24.4 +/- 6.6 kg/m(2), n = 48). METHODS: Measurements were made of the plasma levels of (1) nitrites + nitrates, an indirect measure of available nitric oxide; (2) lipid peroxidation end-products, as malondialdehydes and free thiols; and (3) the redox status of the red blood cell glutathione, as a new oxidative stress parameter. RESULTS: There were decreased plasma levels of nitrates and increased levels of lipid peroxidation end-products in the hypertensive patients, resulting in a consistent increase in the plasma lipid peroxidation/nitric oxide ratio as compared with the controls with the same BMI (P <0.01). This ratio additionally correlated directly with both the systolic and diastolic blood pressures for the overall patient population (P <0.001). A significant glutathione depletion in the red blood cells resulted in an elevated ratio of oxidized/reduced forms with a reduced antioxidant protective capacity in the hypertensive patients versus the BMI-matched controls (P <0.001). CONCLUSIONS: The presence of systemic oxidative stress was proven in hypertensive children and adolescents, irrespective of their BMI.     

Effect of gamma-tocotrienol on blood pressure, lipid peroxidation and total antioxidant status in spontaneously hypertensive rats (SHR)

The aim of this study was to determine the effects of gamma tocotrienol on lipid peroxidation and total antioxidant status of spontaneously hypertensive rats (SHR), comparing them with normal Wistar Kyoto (WKY) rats. SHR were divided into three groups and treated with different doses of gamma tocotrienol (gamma1, 15 mg/kg diet; gamma2, 30 mg/kg diet and gamma3, 150 mg/kg diet). Normal WKY and untreated SHR were used as normal (N) and hypertensive control (HC). Blood pressure were recorded every fortnightly for three months. At the end of the trial, animals were killed and measurement of plasma total antioxidant status, plasma superoxide dismutase (SOD) activity and lipid peroxide levels in plasma and blood vessels were carried out following well established methods. Study shows that lipid peroxides were significantly higher in hypertensive plasma and blood vessels compared to that of normal rats (Plasma- N: 0.06+/-0.01, HC: 0.13+/-0.008; p<0.001, B1. Vessels - N: 0.47+/-0.17, HC: 0.96+/-0.37; p<0.001). SOD activity was significantly lower in hypertensive than normal rats (N = 148.58+/-29.56 U/ml, HC = 110.08+/-14.36 U/ml; p = 0.014). After three months of antioxidant trial with gamma-tocotrienol, it was found that all the treated groups have reduced plasma lipid peroxides concentration but was only significant for group gamma1 (gamma1: 0.109+/-0.026, HC: 0.132+/-0.008; p = 0.034). On the other hand, lipid peroxides in blood vessels reduced significantly in all treated groups (gamma1; p<0.05, gamma2; p<0.001, gamma3; p<0.005). All the three treated groups showed improve total antioxidant status (p<0.001) significantly. SOD activity also showed significant improvement in all groups (gamma1: p<0.001, gamma2: p<0.05, gamma3: p<0.001). Correlation studies showed that, total antioxidant status (TAS) and SOD were significantly negatively correlated with blood pressure in normal rats (p = 0.007; p = 0.008) but not in SHR control. This correlation regained in all three groups SHR's after treatment with tocotrienol. Lipid peroxides in blood vessel and plasma showed a positive correlation with blood pressure in normal and SHR control. This correlation also remains in treated groups significantly except that in gamma3 where positive correlation with plasma lipid peroxide was not significant. In conclusion it was found that antioxidant supplement of gamma-tocotrienol may prevent development of increased blood pressure, reduce lipid peroxides in plasma and blood vessels and enhanced total antioxidant status including SOD activity.     

Antioxidant enzyme activity during prolonged exercise in amenorrheic and eumenorrheic athletes

Exogenous 17 beta-estradiol (E2) has been shown to be associated with elevated levels of erythrocyte glutathione peroxidase (GPX) activity. The purpose of this study was to examine the influence of endogenous E2, as defined by menstrual status (amenorrhea v eumenorrhea), on activity of blood antioxidant enzymes at rest and during prolonged exercise. Six amenorrheic (AMc) and six eumenorrheic (EUc) athletes were subjected to a treadmill running test at 60% VO2max for 90 minutes. Serial blood samples were taken from a forearm vein at rest, 30, 60, and 90 minutes during exercise, and 15 minutes into recovery. Resting estrogen levels were significantly lower in AMc athletes at rest and during exercise as compared with EUc athletes, whereas plasma cortisol levels in AMc were significantly higher. GPX activity was significantly higher in AMc than EUc at rest (46.9 +/- 7.7 v 30.2 +/- 2.2 nmol/min x mg Hb, P less than .05, respectively) and throughout exercise. Glutathione reductase (GR) activity was similar between the two groups at rest and was significantly higher (P less than .01) in AMc than EUc during exercise. Plasma lipid peroxidation and catalase activity did not change significantly in response to exercise, nor were they different between AMc and EUc athletes. GPX activity was found to be negatively correlated with E2 (r = -.64, P less than .01) and positively correlated with cortisol (r = .69, P less than .01). It is tentatively concluded that the alteration of hormonal status in amenorrhea has an influence on the blood antioxidant enzyme system.     

Modulation of nitric oxide synthase activity in brain, liver, and blood vessels of spontaneously hypertensive rats by ascorbic acid: protection from free radical injury

End organ damage in essential hypertension has been linked to increased oxygen free radical generation, reduced antioxidant defense, and/or attenuation of nitric oxide synthase (NOS) activity. Ascorbic acid (AA), a water-soluble antioxidant, has been reported as a strong defense against free radicals in both aqueous and nonaqueous environment. In this study we examined the hypothesis that antioxidant ascorbic acid may confer protection from increased free radical activity in brain, liver, and blood vessels of spontaneously hypertensive rats (SHR). Male SHRs were divided into groups: SHR + AA (treated with AA, 1 mg/rat/day; for 12 weeks) or SHR (untreated). Wister-Kyoto rats (WKY) served as the control. Mean systolic blood pressure (SBP) in treated and untreated SHR was 145 +/- 7 mmHg and 142 +/- 8 mmHg, respectively. AA treatment prevented the increase in systolic blood pressure in SHR by 37 +/- 1% (p < 0.05). NOS activity in the brain, liver, and blood vessels of WKY rat was 1.82 +/- 0.02, 0.14 +/- 0.003, and 1.54 +/- 0.06 pmol citruline/mg protein, respectively. In SHR, total NOS activity was significantly reduced by 52 +/- 1%, 21 +/- 3%, and 44 +/- 4%, respectively. AA increased NOS activity in brain, liver, and blood vessels of SHR from 0.87 +/-.03, 0.11 +/-.01, and 0.87 +/-.08 pmol citruline/mg protein to 0.93 +/- 0.01, 0.13 +/- 0.001, and 1.11 +/- 0.03 pmol citruline/mg protein (p < 0.05), respectively. Lipid peroxides in the brain, liver, and blood vessels from WKY rats were 0.87 +/- 0.06, 0.11 +/- 0.005, and 0.47 +/- 0.04 nmol MDA equiv/mg protein, respectively. In SHR, lipid peroxides in brain, liver, and blood vessels were significantly increased by 40 +/- 3%, 64 +/- 3%, and 104 +/- 13%, respectively. AA reduced lipid peroxidation in liver and blood vessels by 17 +/- 1% and 34 +/- 3% but not in brain. Plasma lipid peroxides were almost doubled in SHR (p < 0.01) together with a reduction in total antioxidant status (6 +/- 0.1%; p < 0.05), nitrite (53 +/- 2%; p < 0.05) and superoxide dismutase (SOD) activity (36 +/- 2%; p < 0.05). AA treatment reduced plasma lipid peroxide (p < 0.001), and increased TAS (p < 0.001), nitrite (p < 0.001), and SOD activity (p < 0.001). From this study, we conclude that brain, liver, and blood vessels in SHR are susceptible to free radical injury, which reduces the availability of NO either by scavenging it or by reducing its production via inhibiting NOS. In addition, brain, liver, and blood vessels in SHR; may be protected by antioxidant, which improves total antioxidant status, and SOD thus may prevent high blood pressure and its complications.     

Regulation of key antioxidant enzymatic systems in the sheep endometrium by ovarian steroids

Reactive oxygen species (ROS) and their control by antioxidant enzymes are involved in the physiology of the female reproductive system. Thus, it is important to understand the regulation of key antioxidant enzymatic pathways. The roles of estrogen and progesterone in regulating the physiological functions of the endometrium have become central dogma. We examined the effects of ovarian steroids on superoxide dismutases (SOD1 and SOD2), catalase (CAT), glutathione peroxidase (GPX), and glutathione reductase (GSR) activities in the aglandular caruncular and glandular inter-caruncular endometrial tissues of ovariectomized (OVX) ewes and in OVX ewes treated with estradiol (E2), progesterone (P4), or both hormones according to schedules designed to produce physiological changes of these hormones during the estrous cycle. The activities SOD2, CAT, GPX and GSR in both endometrial tissues were unaffected by P4 treatment. The activity of SOD1 in the aglandular tissue was unaffected by P4 treatment, however this treatment decreased SOD1 activity in the glandular tissue (P < 0.01). Treatment with E2, either alone or in combination with P4, decreased SOD1 (P < 0.01), CAT (P < 0.01) and GPX (P < 0.05) activities in both endometrial tissues. The activity of GSR decreased only in the glandular tissue (P < 0.05) after E2 treatment, either alone or in combination with P4. No change in SOD2 activity was detected in both endometrial tissues after administration of E2, P4 or both hormones. This study provides the first firm evidence for the role of ovarian steroid hormones in the regulation of the activities of key antioxidant enzyme in the endometrium of female mammals.