Expression of catalase and glutathione peroxidase in renal insufficiency

Chronic renal failure (CRF) is associated with oxidative stress, the precise mechanism of which is yet to be elucidated. The present study was undertaken to investigate in renal insufficiency the expression of catalase and glutathione peroxidase, which play a critical role in antioxidant defense system by catalyzing detoxification of hydrogen peroxide (H2O2) and organic hydroperoxides. Rats were randomly assigned to the CRF (5/6 nephrectomized) and sham-operated control groups and observed for 6 weeks. Renal and thoracic aortic catalase and glutathione peroxidase protein abundance was measured by Western blotting. The enzyme activities in the renal and aortic extracts, hepatic glutathione levels, blood pressure and urinary nitric oxide metabolites (NO(x)) excretion were also measured. Blood pressure and urinary nitric oxide metabolite (NO(x)) excretion were also measured. The CRF group showed a significant down-regulation of both immunodetectable catalase and glutathione peroxidase proteins in the remnant kidney. Catalase activity was also significantly decreased in the remnant kidney whereas glutathione peroxidase activity was not significantly affected. Furthermore, the protein abundance of catalase was unchanged whereas the enzyme activity was significantly decreased in the thoracic aorta of CRF animals compared to the sham-operated controls. By contrast, both the protein abundance and the enzyme activity of glutathione peroxidase were not significantly affected in the aorta of CRF animals compared to the sham-operated controls. This was coupled with marked arterial hypertension, significant reduction of hepatic glutathione levels and urinary NO(x) excretion pointing to increased inactivation and sequestration of NO by superoxide. These events point to the role of impaired antioxidant defense system in the pathogenesis of oxidative stress in CRF.     

Glutathione level and its relation to radiation therapy in patients with cancer of uterine cervix

Glutathione functions as an important antioxidant in the destruction of hydrogen peroxide and lipid peroxides by providing substrate for the glutathione peroxidase and also promotes the ascorbic acid. Glutathione plays a vital role in detoxification of xenobiotics, carcinogens, free radicals and maintenance of immune functions. The study was aimed to determine plasma glutathione as well as erythrocyte glutathione and glutathione peroxidase in patients with invasive cervical carcinoma (n = 30) before initiation and after completion of radiotherapy and subsequently, at the time of first three monthly follow-up visit. The levels of plasma glutathione, erythrocyte glutathione and glutathione peroxidase activity were found to be lower in all cervical cancer patients as compared to age matched normal control women. The study indicates a change in antioxidant status in relation with the glutathione system among patients with invasive carcinoma of the uterine cervix. This study also demonstrates the effect of radiation therapy on this antioxidant system.     

外源一氧化氮对镉胁迫下绿豆幼苗根尖抗氧化酶的影响

采用水培法研究外源一氧化氮对镉(Cd)胁迫下绿豆幼苗根尖抗氧化酶活性的影响。结果表明:0.01mmol/L和0.1mmol/L一氧化氮供体硝普钠(sodium nitroprusside,SNP)显著促进上胚轴生长,1mmol/LSNP则抑制绿豆幼苗生长。Cd单独处理抑制根尖抗坏血酸过氧化物酶(ascorbate peroxidase,APX)和超氧化物歧化酶(superoxide dismutase,SOD)活性而刺激脂氧合酶(lipoxygenase,LOX)、谷胱甘肽转硫酶(glutathione S-transferase,GST)、谷胱甘肽还原酶(glutathione reductase,GR)和过氧化物酶(guaiacol peroxidase,POD)活性上升。0.1mmol/LSNP预处理能够明显缓解Cd对根生长的抑制,降低根尖中MDA含量,提高根尖APX和SOD活性,降低LOX和POD活性,但不影响GST和GR活性。     

Opposing roles for superoxide and nitric oxide in the NaCl stress-induced upregulation of antioxidant enzyme activity in cotton callus tissue

The roles of superoxide and NO in the NaCl-induced upregulation on antioxidant enzyme activity were investigated in NaCl-tolerant cotton calli. Both NaCl and paraquat treatments resulted in significant increases in superoxide production. The activities of ascorbate peroxidase (APX), catalase, glutathione reductase (GR), and peroxidase also increased significantly within 2 h after applying the stress. Pre-treatment with the superoxide scavenger, N-acetyl l-cysteine (NAC), completely removed the superoxide and inhibited the upregulation of antioxidant enzyme activity in the tissue treated with either NaCl or paraquat. NaCl stress also resulted in a significant increase in the NO level. Experiments were also carried out to measure antioxidant enzyme activity in cotton calli exposed to NO, the NO producer sodium nitroprusside (SNP), and the NO scavenger 2-phenyl-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide (PTIO) under different salt stress conditions. The direct addition of NO gas produced no change in the activities of catalase and GR and caused a significant decrease in APX activity when compared to the controls. When the calli was treated with SNP in the absence of NaCl stress, APX and GR activities decreased significantly and catalase activity was only slightly higher than the control. Treatment with SNP in the presence of NaCl stress resulted in a significant decrease in APX activity, and GR and APX activities were not significantly different from those observed in the NaCl treatment alone. In the presence of PTIO, the activities of all three enzymes increased in the presence or absence of NaCl stress. These results suggest that reactive oxygen species (ROS) such as superoxide radicals may serve as signal transduction molecules to switch “on” the early NaCl-induced up-regulation of antioxidant enzyme activity, while NO may play a role in switching “off” the response after other mechanisms in the cascade of events responsible for NaCl tolerance have been activated.     

Reactive oxygen species are key mediators of the nitric oxide apoptotic pathway in anterior pituitary cells.

We previously showed that long-term exposure of anterior pituitary cells to nitric oxide (NO) induces apoptosis. The intracellular signals underlying this effect remained unclear. In this study, we searched for possible mechanisms involved in the early stages of the NO apoptotic cascade. Caspase 3 was activated by NO with no apparent disruption of mitochondrial membrane potential. NO caused a rapid increase of reactive oxygen species (ROS), and this increase seems to be dependent of mitochondrial electron transport chain. The antioxidant N-acetyl-cysteine avoided ROS increase, prevented the NO-induced caspase 3 activation, and reduced the NO apoptotic effect. Catalase was inactivated by NO, while glutathione peroxidase (GPx) activity and reduced glutathione (GSH) were not modified at first, but increased at later times of NO exposure. The increase of GSH level is important for the scavenging of the NO-induced ROS overproduction. Our results indicate that ROS have an essential role as a trigger of the NO apoptotic cascade in anterior pituitary cells. The permanent inhibition of catalase may strengthen the oxidative damage induced by NO. GPx activity and GSH level augment in response to the oxidative damage, though this increase seems not to be enough to rescue the cells from the NO effect.     

Changes in the antioxidant systems as part of the signaling pathway responsible for the programmed cell death activated by nitric oxide and reactive oxygen species in tobacco Bright-Yellow 2 cells

Nitric oxide (NO) has been postulated to be required, together with reactive oxygen species (ROS), for the activation of the hypersensitive reaction, a defense response induced in the noncompatible plant-pathogen interaction. However, its involvement in activating programmed cell death (PCD) in plant cells has been questioned. In this paper, the involvement of the cellular antioxidant metabolism in the signal transduction triggered by these bioactive molecules has been investigated. NO and ROS levels were singularly or simultaneously increased in tobacco (Nicotiana tabacum cv Bright-Yellow 2) cells by the addition to the culture medium of NO and/or ROS generators. The individual increase in NO or ROS had different effects on the studied parameters than the simultaneous increase in the two reactive species. NO generation did not cause an increase in phenylalanine ammonia-lyase (PAL) activity or induction of cellular death. It only induced minor changes in ascorbate (ASC) and glutathione (GSH) metabolisms. An increase in ROS induced oxidative stress in the cells, causing an oxidation of the ASC and GSH redox pairs; however, it had no effect on PAL activity and did not induce cell death when it was generated at low concentrations. In contrast, the simultaneous increase of NO and ROS activated a process of death with the typical cytological and biochemical features of hypersensitive PCD and a remarkable rise in PAL activity. Under the simultaneous generation of NO and ROS, the cellular antioxidant capabilities were also suppressed. The involvement of ASC and GSH as part of the transduction pathway leading to PCD is discussed.     

Nitric oxide synthase like activity-dependent nitric oxide production protects against chilling-induced oxidative damage in Chorispora bungeana suspension cultured cells

In the present study, we used suspension cultured cells from Chorispora bungeana Fisch. and C.A. Mey to investigate whether nitric oxide (NO) is involved in the signaling pathway of chilling adaptive responses. Low temperatures at 4 °C or 0 °C induced ion leakage, lipid peroxidation and cell viability suppression, which were dramatically alleviated by exogenous application of NO donor sodium nitroprusside (SNP). The levels of reactive oxygen species (ROS) were obviously reduced, and the activities of antioxidant enzymes such as ascorbate peroxidase (APX, EC 1.11.1.11), catalase (CAT, EC 1.11.1.6), glutathione reductase (GR, EC 1.6.4.2), peroxidase (POD, EC 1.11.1.7) and superoxide dismutase (SOD, EC 1.15.1.1) and the contents of ascorbic acid (AsA) and reduced glutathione (GSH) increased evidently in the presence of SNP under chilling stress. In addition, under low temperature conditions, treatment with NO scavenger PTIO or mammalian NO synthase (NOS) inhibitor l-NAME remarkably aggravated oxidative damage in the suspension cultures compared with that of chilling treatment alone. Moreover, measurements of NOS activity and NO production showed that both NOS activity and endogenous NO content increased markedly under chilling stress. The accumulation of NO was inhibited by l-NAME in chilling-treated cultures, indicating that most NO production under chilling may be generated from NOS-like activity. Collectively, these results suggest that chilling-induced NO accumulation can effectively protect against oxidative injury and that NOS like activity-dependent NO production might act as an antioxidant directly scavengering ROS or operate as a signal activating antioxidant defense under chilling stress, thus conferring an increased tolerance to chilling in C. bungeana suspension cultures.     

Characteristics of the antioxidant system of alveolar surfactant in immediate-type allergies

The antioxidant system (glutathione peroxidase, glutathione reductase, superoxide dismutase, total antioxidant activity) of the lung surfactant has been studied for and intensity of peroxidation in that surfactant after administration of sensitizing and resolving doses of the allergen to animals. An increase in the amount of lipid peroxidation products as well as in activity of superoxide dismutase followed by a fall of gamma-glutamyl transpeptidase activity was observed in the lung surfactant 3 and 12 days after introduction of a sensitizing dose of the allergen. Intensification of 5-lipoxygenase activity and accumulation of malonic dialdehyde in the lung surfactant under the anaphylactic shock were accompanied by inhibition of activity of the glutathione-dependent antioxidant system glutathione reductase and glutathione peroxidase) as well as by a fall of antioxidative activity of the surfactant. The data obtained have evidenced for a imbalance between the induction and metabolism systems of lipid hydroperoxides in the respiratory organs under immediate allergies.     

Antioxidant actions of nitroxyl (HNO)

Nitrogen oxides are endogenously produced signaling/effector molecules that have the potential to both cause and ameliorate oxidative stress. Whether nitrogen oxides behave as oxidants or antioxidants is dependent on many factors including the cellular environment, the concentration, and the presence of other reactive species. To date, the nitrogen oxide nitroxyl (HNO) has only been reported to possess prooxidant properties. However, some of its chemical properties would predict that it could also serve as an antioxidant. In this study, the possible antioxidant actions of HNO were examined using the yeast Saccharomyces cerevisiae model system. The effect of HNO on membrane lipid peroxidation was examined and HNO was determined to act solely as an antioxidant in this system. In the presence of glutathione, a thiol-containing peptide that scavenges HNO, the antioxidant action was decreased. In addition, the antioxidant properties of HNO were not due to the conversion of HNO to NO. These results were also confirmed with in vitro assays of oxidative stress. Thus, HNO has the potential to preserve lipid membrane integrity by its antioxidant actions.     

Dietary glycine inhibits activation of nuclear factor kappa B and prevents liver injury in hemorrhagic shock in the rat.

We investigated the effects of a glycine-containing diet (5%) on liver injury caused by hemorrhagic shock and resuscitation in rats. Anesthetized rats were bled to a mean arterial blood pressure of 35-40 mm Hg for 1 h and then resuscitated with 60% of shed blood and lactated Ringer's solution. Feeding the rats glycine significantly reduced mortality, the elevation of plasma transaminase levels and hepatic necrosis. The increase in plasma TNFalpha and nitric oxide (NO) was also blunted by glycine feeding. Hemorrhagic shock resulted in oxidative stress (significant elevations in TBARS and in the oxidized/reduced glutathione ratio) and was accompanied by a reduced activity of the antioxidant enzymes Mn- and Cu,Zn-superoxide dismutase, glutathione peroxidase and catalase, overexpression of inducible NO synthase (iNOS), and activation of nuclear factor kappa B (NF-kappaB). Glycine ameliorated oxidative stress and the impairment in antioxidant enzyme activities, inhibited NF-kappaB activation, and prevented expression of iNOS. Dietary glycine blocks activation of different mediators involved in the pathophysiology of liver injury after shock.     

The state of the antioxidant system during therapy of patients with multiple sclerosis

Activity of erythrocyte glutathione peroxidase (GPx), glutathione reductase (GR), glutathione transferase (GT), glucose-6-phosphate dehydrogenase (G6PDH), catalase and superoxide dismutase (SOD), the level of erythrocyte malonic dialdehyde (MDA) and also total antioxidant activity of blood serum were studied in patients with different types of multiple sclerosis (MS). Investigation of peripherical blood was carried out on the first day of admission to the hospital and after the standard therapy with copaxone. During the whole period of observation all MS patients had a high level of MDA and activity of erythrocyte GP compared with a control group. Other erythrocyte antioxidant enzymes and total antioxidant activity of blood serum exhibited weak positive dynamics in patients with relapsing-remitting multiple sclerosis (RRMS). The pathological decrease of antioxidant system activity in patients with secondary progressive multiple sclerosis (SPMS) was more pronounced and remained unchanged after the treatment. This is consistent with a more severe clinical course of this disease.     

Glutathione and ascorbic acid metabolism and antioxidant enzyme activity in the tissues of vitamin E-deficient rats

In has been shown in the experiments on male rats that alimentary vitamin E deficit causes the decrease of reduced glutathione and ascorbic acid concentration in the liver and lungs and that of glutathione-S-transferase, glutathione reductase in the liver and lungs, catalase in the liver and glutathione peroxidase in the heart activity, but increases the amount of glutathione disulfide in the liver and lungs and superoxide dismutase and gamma-glutamyltransferase activity in the liver. The data obtained show the selective character of reaction participants of the antioxidant system of rats' organism to the deficit of one of the antioxidant factors--vitamin E and also testify to complex interrelation between separate members of this system.     

Activity of the glutathione antioxidant system and cytochrome P-450 in rat liver under induction and inhibition of xanthine oxidase

The effects of specific xanthine oxidase induction and inhibition on glutathione antioxidant system activity, lipid peroxidation, cytochrome P-450 quantity and corticosteroids concentration in the rat liver were studied. It was dependence established that there was a straight between xanthine oxidase activity and the activity of glutathione antioxidant system, lipid peroxidation and the ascorbic acid formation. The reciprocal dependence was established between xanthine oxidase activity and the concentrations of cytochrome P-450 and corticosteroids.     

Oxidative injury due to chronic nitric oxide synthase inhibition in rat: effect of regular exercise on the heart

Many individuals with cardiac diseases undergo periodic physical conditioning with or without medication. Therefore, this study investigated the interaction of physical training and chronic nitric oxide synthase (NOS) inhibitor (nitro-L-arginine methyl ester, L-NAME) treatment on blood pressure (BP), heart rate (HR) and cardiac oxidant/antioxidant systems in rats. Fisher 344 rats were divided into four groups and treated as follows: (1) sedentary control (SC), (2) exercise training (ET) for 8 weeks, (3) L-NAME (10 mg/kg, s.c. for 8 weeks) and (4) ET+L-NAME. BP and HR were monitored with tail-cuff method. The animals were sacrificed 24 h after last treatments and hearts were isolated and analyzed. Physical conditioning significantly increased respiratory exchange ratio (RER), cardiac nitric oxide (NO) levels, NOS activity and endothelial (eNOS) and inducible (iNOS) protein expression. Training significantly enhanced cardiac glutathione (GSH) levels, GSH/GSSG ratio and up-regulation of cardiac copper/zinc-superoxide dismutase (CuZn-SOD), manganese (Mn)-SOD, catalase (CAT), glutathione peroxidase (GSH-Px) activity and protein expression. Training also caused depletion of cardiac malondialdehyde (MDA) and protein carbonyls. Chronic L-NAME administration resulted in depletion of cardiac NO level, NOS activity, eNOS, nNOS and iNOS protein expression, GSH/GSSG ratio and down-regulation of cardiac CuZn-SOD, Mn-SOD, CAT, GSH-PX, glutathione-S-transferase (GST) activity and protein expression. Chronic L-NAME administration enhanced cardiac xanthine oxidase (XO) activity, MDA levels and protein carbonyls. These biochemical changes were accompanied by increases in BP and HR after L-NAME administration. Interaction of training and NOS inhibitor treatment resulted in normalization of BP, HR and up-regulation of cardiac antioxidant defense system. The data suggest that physical conditioning attenuated the oxidative injury caused by chronic NOS inhibition by up-regulating the cardiac antioxidant defense system and lowering the BP and HR in rats.     

Protective influence of vitamin E on antioxidant defense system in the blood of rats treated with cadmium

The effects of acute exposure to cadmium (Cd) on the blood antioxidant defense system, lipid peroxide concentration and hematological parameters, as well as the possible protective role of vitamin E were studied. Male Wistar albino rats (3 months old) were treated with cadmium (0.4 mg Cd/kg b.m., i.p., 24 h before the experiment) or with vitamin E + Cd (20 IU Vit E/kg b.m., i.m., 48 h + 0.4 mg Cd/kg b.m., i.p., 24 h before the experiment). The hematological parameters were assessed: red blood cell counts, hematocrit value and hemoglobin concentration were significantly decreased in the blood of Cd-treated rats. Intoxication with cadmium was also followed by significantly increased lipid peroxide concentrations. We also observed increased activity of antioxidant defense enzymes: copper zinc containing superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase as well as concentrations of non-enzymatic components of antioxidant defense system: reduced glutathione, vitamin C and vitamin E. Pretreatment with vitamin E exhibited a protective role on the toxic effects of cadmium on the hematological values, lipid peroxide concentration as well as on enzymatic and non-enzymatic components of antioxidant defense system.     

Salicylic acid and nitric oxide alleviate osmotic stress in wheat (Triticum aestivum L.) seedlings

Salicylic acid (SA) and nitric oxide (NO) are reported to alleviate the damaging effects of stress in plants rather similarly when applied at appropriate low concentrations. An experiment was therefore conducted to study the impact of SA, sodium nitroprusside (SNP; as NO donor), and methylene blue (MB; as a guanylate cyclase inhibitor) on wheat seedling performance under osmotic stress. Osmotic stress significantly reduced shoot fresh weight (SFW), chlorophyll contents (Chla, Chlb, total Chl), and membrane stability index (MSI) and also increased malondialdehyde (MDA) level, lipoxygenase (LOX) activity, and hydrogen peroxide production. Moreover, enzymatic antioxidant activities including superoxide dismutase, guaiacol peroxidase, and glutathione reductase activity were enhanced under osmotic stress. On the contrary, SA or SNP pretreatment reduced the damaging effects of osmotic stress by further enhancing the antioxidant activities that led to increased SFW, Chl, and MSI and reduced MDA level and LOX activity. However, pretreatment of plants with MB reversed or reduced the protective effects of SA and SNP suggesting that the protective effects were likely attributed to NO signaling. Therefore, NO may act as downstream of SA signaling in reduction of induced oxidative damage in wheat seedlings.     

Glutathione depletion switches nitric oxide neurotrophic effects to cell death in midbrain cultures: implications for Parkinson's disease

Nitric oxide (NO) exerts neurotrophic and neurotoxic effects on dopamine (DA) function in primary midbrain cultures. We investigate herein the role of glutathione (GSH) homeostasis in the neurotrophic effects of NO. Fetal midbrain cultures were pretreated with GSH synthesis inhibitor, l ‐buthionine‐(S,R)‐sulfoximine (BSO), 24 h before the addition of NO donors (diethylamine/nitric oxide‐complexed sodium and S‐nitroso‐N‐acetylpenicillamine) at doses tested previously as neurotrophic. Under these conditions, the neurotrophic effects of NO disappeared and turned on highly toxic. Reduction of GSH levels to 50% of baseline induced cell death in response to neurotrophic doses of NO. Soluble guanylate cyclase (sGC) and cyclic GMP‐dependent protein kinase (PKG) inhibitors protected from cell death for up to 10 h after NO addition; the antioxidant ascorbic acid also protected from cell death but its efficacy decreased when it was added after NO treatment (40% protection 2 h after NO addition). The pattern of cell death was characterized by an increase in chromatin condensed cells with no DNA fragmentation and with breakdown of plasmatic membrane. The inhibition of RNA and protein synthesis and of caspase activity also protected from cell death. This study shows that alterations in GSH levels change the neurotrophic effects of NO in midbrain cultures into neurotoxic. Under these conditions, NO triggers a programmed cell death with markers of both apoptosis and necrosis characterized by an early step of free radicals production followed by a late requirement for signalling on the sGC/cGMP/PKG pathway.     

Nitric oxide modulates antioxidant defense and the methylglyoxal detoxification system and reduces salinity-induced damage of wheat seedlings

The present study investigates the possible regulatory role of exogenous nitric oxide (NO) in antioxidant defense and methylglyoxal (MG) detoxification systems of wheat seedlings exposed to salt stress (150 and 300 mM NaCl, 4 days). Seedlings were pre-treated for 24 h with 1 mM sodium nitroprusside, a NO donor, and then subjected to salt stress. The ascorbate (AsA) content decreased significantly with increased salt stress. The amount of reduced glutathione (GSH) and glutathione disulfide (GSSG) and the GSH/GSSG ratio increased with an increase in the level of salt stress. The glutathione S-transferase (GST) activity increased significantly with severe salt stress (300 mM). The ascorbate peroxidase (APX), monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR), catalase (CAT) and glutathione peroxidase (GPX) activities did not show significant changes in response to salt stress. The glutathione reductase (GR), glyoxalase I (Gly I), and glyoxalase II (Gly II) activities decreased upon the imposition of salt stress, especially at 300 mM NaCl, with a concomitant increase in the H₂O₂ and lipid peroxidation levels. Exogenous NO pre-treatment of the seedlings had little influence on the non-enzymatic and enzymatic components compared to the seedlings of the untreated control. Further investigation revealed that NO pre-treatment had a synergistic effect; that is, the pre-treatment increased the AsA and GSH content and the GSH/GSSG ratio, as well as the activities of MDHAR, DHAR, GR, GST, GPX, Gly I, and Gly II in most of the seedlings subjected to salt stress. These results suggest that the exogenous application of NO rendered the plants more tolerant to salinity-induced oxidative damage by enhancing their antioxidant defense and MG detoxification systems.     

Exercise conditioning attenuates the hypertensive effects of nitric oxide synthase inhibitor in rat

Many individuals with cardiovascular diseases undergo periodic exercise conditioning with or with out medication. Therefore, this study investigated the interaction of exercise training and chronic nitric oxide synthase (NOS) inhibitor (Nitro-L-Arginine Methyl Ester, L-NAME) treatment on blood pressure and its correlation with aortic nitric oxide (NO), antioxidant defense system and oxidative stress parameters in rats. Fisher 344 rats were divided into four groups: (1) sedentary control, (2) exercise training (ET) for 8 weeks, (3) L-NAME (10 mg/kg, subcutaneous for 8 weeks) and (4) ET + L-NAME. Blood pressure (BP) was monitored weekly for 8 weeks with tail-cuff method. The animals were sacrificed 24 h after last treatments and thoracic aortic rings were isolated and analyzed. Exercise conditioning resulted in a significant increase in respiratory exchange ratio (RER), aortic NO production, NO synthase activity and inducible iNOS protein expression. Training significantly enhanced aortic GSH levels, GSH/GSSG ratio and up-regulation of aortic CuZn-SOD, Mn-SOD, catalase (CAT) glutathione peroxidase (GSH-Px) activity and protein expression and significantly decreased aortic lipid peroxidation. Chronic L-NAME administration resulted in a significant depletion of aortic NO, NOS activity, endothelial (eNOS) and iNOS protein expression, GSH level, GSH/GSSG ratio, down-regulation of aortic antioxidant enzyme activities and protein expressions. Aortic xanthine oxidase (XO) activity significantly increased with increased lipid peroxidation and protein oxidation after L-NAME administration. The biochemical changes were accompanied by increased in BP. Interaction of training and chronic NOS inhibitor treatment resulted in normalization of BP and aortic antioxidant enzyme activity and protein expression, up-regulation of aortic GSH/GSSG ratio, NO levels, Mn-SOD protein expression, depletion of GSSG, protein oxidation and lipid peroxidation. The data suggest that training attenuated the oxidative injury caused by chronic NOS inhibitor treatment by up-regulating the NO and antioxidant systems and lowering the BP in rats.