UMLS:C0406810 - FACTA Search

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Query: UMLS:C0406810 (NAME)
13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antioxidant effect of the non-specific nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (CAS 50903-99-6, L-NAME), was studied in a rat model of global cerebral ischemia. In addition, the influence of low doses of L-NAME on nitric oxide production, measured as nitrate/nitrite end products, was investigated in the ischemic rats. Ischemia was induced by bilateral clamping of the common carotid arteries for 60 min followed by a reperfusion period for 60 min. L-NAME was administered intraperitoneally in the doses of 1 and 3 mg kg-1, twice, immediately after ischemia and 15 min before termination of the experiment. The drug decreased the elevated activity of lactate dehydrogenase (LDH, 1.1.1.27) as well as the increased level of lipid peroxide in the rat brain. L-NAME was also capable to normalize the reduced activity of superoxide dismutase (SOD, 1.15.1.1) that was observed after ischemia. Improvement of these parameters in L-NAME-treated rats was parallel to normalization of nitric oxide production in the treated animals. These results indicate that inhibition of nitric oxide synthase, induced by L-NAME, could improve the oxidative status of the rat brain after ischemia.
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PMID:Antioxidant effect of N omega-nitro-L-arginine methyl ester (L-NAME) on global cerebral ischemia in a rat model. 1155 22

Vascular endothelial growth factor (VEGF) is a potent vascular endothelial cell-specific mitogen that modulates endothelial cell function. In the present study, we show that VEGF induces manganese-superoxide dismutase (MnSOD) mRNA and protein in human coronary artery endothelial cells (HCAEC) and pulmonary artery endothelial cells. VEGF-mediated induction of MnSOD mRNA was inhibited by pretreatment with the NADPH oxidase inhibitors, diphenyleneiodonium (DPI), and 4-(2-aminoethyl)-benzenesulfonyl fluoride, but not with the nitric oxide synthase inhibitor L-NAME (N-monomethyl-L-arginine) or the xanthine oxidase inhibitor allopurinol. VEGF stimulation of MnSOD was also inhibited by adenoviral-mediated overexpression of catalase Cu, Zn-SOD and a dominant-negative form of the small GTPase component of NADPH oxidase Rac1 (Rac1N17). Treatment of HCAEC with VEGF resulted in a transient increase in ROS production at 20 min, as measured by 2,7-dichlorodihydrofluorescein oxidation. This effect was abrogated by expression of Rac1N17. Taken together, these findings suggest that VEGF induces MnSOD by an NADPH oxidase-dependent mechanism and that VEGF signaling in the endothelium is coupled to the redox state of the cell.
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PMID:Vascular endothelial growth factor induces manganese-superoxide dismutase expression in endothelial cells by a Rac1-regulated NADPH oxidase-dependent mechanism. 1164 Dec 65

Nitric oxide (NO) has been proved to be a mediator of hypoxic injury in renal proximal tubules (PT), but its effect on iron-induced cytotoxicity has remained little known. In this study, we observed the relationship between NO production and lactate dehydrogenase (LDH) release in primary proximal tubular epithelia co-incubated with different doses of NTA-Fe and lipopolysaccharide (LPS) alone or in combination. NO production was monitored by NO2 concentration in supernatants based on the Griess reaction; while the semi-quantitative RT-PCR was applied to detect the inducible nitric oxide synthase (iNOS) mRNA level induced by NTA-Fe and LPS together. In addition, experimental groups were subjected to reactive oxygen species (ROS) scavengers to determine the impact of the interaction between NO and ROS on iron-mediated cytotoxicity. After a 12-h co-incubation, we found that NTA-Fe increased both LDH release and NO2(-) production in a dose-dependent manner (P < 0.001). The level of iNOS mRNA induced by LPS was enhanced by 500 microM NTA-Fe (P < 0.01), lower or higher concentrations had no effect. However, the supernatantNO2(-) level in the same group did not change significantly (P > 0.05) although tubular injury was aggravated (P < 0.001). The addition of L-arginine increased LDH release from 25.05 +/- 8.36% in the iron group to 38.67 +/- 7.67% in iron plus LPS group (P < 0.05); concomitantly, L-NAME mitigated iron toxicity in LPS-treated PT (P < 0.05). Hydroxyl scavengers provided complete protection against iron-mediated cytotoxicity (P < 0.001), but the decrease of NO2(-) production was only significant in the LPS-treated group. In contrast, SOD was partially effective in the LPS group (P < 0.05) whereas the NO2(-) level in the supernatant was inversely raised (P < 0.05). GSH had no effect on either iron toxicity or NO2(-) production. Thus, we conclude that NO can exacerbate the cytotoxicity caused by NTA-Fe in cultured proximal tubular epithelia, but NO is not the only factor. NTA-Fe could enhance the upregulation of iNOS transcription induced by LPS in a specific concentration range, and its regulation of NO production might also involve a post-transcription mechanism. The hydroxyl group is the major mediator in our model and the pro-oxidant role of NO is probably due to its ability to promote the Fenton reaction and form both ONOO(-) and *OH via its interaction with ROS.
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PMID:Effect of nitric oxide on iron-mediated cytotoxicity in primary cultured renal proximal tubules. 1174 4

AIM:To study relationship of injury induced by nitric oxide, oxidation, peroxidation,lipoperoxidation with chronic cholecystitis.METHODS:The values of plasma nitric oxide (P-NO), plasma vitamin C (P-VC), plasma vitamin E (P-VE), plasma beta-carotene (P-beta-CAR), plasma lipoperoxides (P-LPO), erythrocyte superoxide dismutase (E-SOD), erythrocyte catalase (E-CAT), erythrocyte glutathione peroxidase (E-GSH-Px) activities and erythrocyte lipoperoxides (E-LPO) level in 77 patients with chronic cholecystitis and 80 healthy control subjects were determined, differences of the above average values between the patient group and the control group and differences of the average values between preoperative and postoperative patients were analyzed and compared, linear regression and correlation of the disease course with the above determination values as well as the stepwise regression and correlation of the course with the values were analyzed.RESULTS:Compared with the control group, the average values of P-NO, P-LPO, E-LPO were significantly increased (P<0.01), and of P-VC, P-VE, P-beta-CAR, E-SOD, E-CAT and E-GSH-Px decreased (P <0.01) in the patient group. The analysis of the linear regression and correlation showed that with prolonging of the course, the values of P-NO, P-LPO and E-LPO in the patients were gradually ascended and the values of P-VC,P-VE, P-beta-CAR, E-SOD, E-CAT and E-GSH-Px descended (P<0.01). The analysis of the stepwise regression and correlation indicated that the correlation of the course with P-NO, P-VE and P-beta-CAR values was the closest. Compared with the preoperative patients, the average values of P-NO, P-LPO and E-LPO were significantly decreased (P <0.01) and the average values of P-VC, E-SOD, E-CAT and E-GSH-Px in postoperative patients increased (P <0.01) in postoperative patients. But there was no significant difference in the average values of P-VE, P-beta-CAR preoperative and postoperative patients.CONCLUSION:Chronic cholecystitis could induce the increase of nitric oxide, oxidation, peroxidation and lipoperoxidation.
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PMID:A study on relationship of nitric oxide, oxidation, peroxidation, lipoperoxidation with chronic chole-cystitis. 1181 37

Plasma vitamin C(P-VC), vitamin E(P-VE) and beta-carotene(P-beta-CAR) contents and the activities of superoxide dismutase(E-SOD), catalase(E-CAT) and glutathione peroxidase (E-GSH-Px) in erythrocyte in 73 silicosis patients and 60 healthy control subjects were measured. The average levels of P-VC, P-VE, P-beta-CAR, E-SOD, E-CAT and E-GSH-Px of patients were significantly lower than those of the controls (P < 0.001). All indexes were correlated to the course, condition and pulmonary function of silicosis patients. The results analyzed by stepwise regression showed that the correlation between course, condition and pulmonary function of patients and P-VE and E-SOD was close. The balance between oxidation and the antioxidation in silicosis patients may be disturbed, and oxygen free radical reaction may be pathologically exacerbated.
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PMID:[Study on the correlation of silicosis with antioxidant and antioxidase]. 1193 4

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.
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PMID:Exercise conditioning attenuates the hypertensive effects of nitric oxide synthase inhibitor in rat. 1195 54

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.
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PMID:Oxidative injury due to chronic nitric oxide synthase inhibition in rat: effect of regular exercise on the heart. 1200 27

Nitric oxide (NO) has been implicated as a mediator of vasodilation and neurotransmission in the mammalian cochlea. This is demonstrated by the presence of nitric oxide synthase (NOS) and nitric oxide (NO) in the blood vessels and the organ of Corti in the cochlea. It is not certain if the neurons in the spiral ganglion produce NO since no fluorescent signal could be detected by 4,5-diaminofluorescein diacetate (DAF-2DA), a fluorescent indicator of NO. To determine if NO/peroxynitrite plays any role in neurodestruction observed in ischemic cochlea of the guinea pig, the effects of NO donors, such as S-nitrosocysteine (S-NC) and nitroglycerine (NTG); peroxynitrite generators, such as 3-morpholinosydnonimine (SIN-1); peroxynitrite inhibitors, such as superoxide dismutase plus catalase (SOD/Cat); and NOS inhibitors, such as N(G)-nitro-L-arginine methyl ether (L-NAME) were tested on normal and ischemic cochleae. The level of NO in the cochlea after 20 to 120 minutes of ischemia was indicated by measurement of nitrites/nitrates in the perilymph. The evidence gathered from these experiments indicates that NO or peroxynitrite is not necessarily destructive to auditory hair cells, and in fact, exogenous NO may protect neural structures in the cochlea from damage under ischemic conditions.
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PMID:Possible roles of nitric oxide in the physiology and pathophysiology of the mammalian cochlea. 1207 80

Using spontaneously hypertensive rats (SHR) fed a standard or a Zn-deficient diet for 4 weeks, we examined whether Zn deficiency affects systemic blood pressure (BP) levels in a genetically hypertensive state through a fall in the activity of Cu/Zn-superoxide dismutase (SOD). SHR fed a Zn-deficient diet had a progressive increase in systolic BP during the dietary conditioning. Consequently, SHR fed a Zn-deficient diet exhibited significantly increased levels of systolic BP by 2 weeks after the start of dietary treatment when compared with SHR fed a standard diet. Similarly, levels of basal mean arterial pressure (MAP) observed at the end of dietary treatment were SHR fed a Zn-deficient diet > SHR fed a standard diet. Administration of the nitric oxide synthase (NOS) inhibitor, L-NAME, caused an increase in MAP levels in the two groups of rats, demonstrating the involvement of the vasodilator, nitric oxide (NO), in the regulation of systemic BP in a genetically hypertensive state. The expression of endothelial (e) NOS mRNA and protein in the thoracic aorta paralleled basal MAP levels in the two groups of rats, suggesting the counter-regulation of eNOS against the developed hypertensive state in SHR fed a Zn-deficient diet. On the other hand, administration of the superoxide scavenger, tempol (a SOD mimetic compound), led to a decrease in MAP levels in the two groups of rats, indicating the participation of the oxygen free radical, superoxide, in an increase in systemic BP in a genetically hypertensive state. As reported recently, the mechanism involved is due likely to a decrease in the action of the vasodilator, NO, based on the formation of peroxynitrite coming from the non-enzymatic reaction of superoxide and NO. In addition, tempol treatment completely restored MAP levels in SHR fed a Zn-deficient diet to levels comparable to those observed in SHR fed a standard diet, indicating that a further increase in systemic BP levels seen in SHR fed a Zn-deficient vs. a standard diet is presumably brought by a reduction in the action of the vasodilator, NO, resulting from an increase in the action of superoxide. The activity of the superoxide scavenger, Cu/Zn-SOD, in the thoracic aorta was significantly decreased in SHR fed a Zn-deficient diet relative to SHR fed a standard diet. It appears that a decrease in the activity of Cu/Zn-SOD observed in the thoracic aorta of SHR fed a Zn-deficient diet at least in part plays a role in an increase in the action of superoxide in this model. Thus, Zn deficiency may be a factor to develop genetic hypertension presumably through the oxidative stress caused by superoxide.
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PMID:Zn deficiency aggravates hypertension in spontaneously hypertensive rats: possible role of Cu/Zn-superoxide dismutase. 1210 76

Endogenous reactive oxygen species (superoxide anion, hydroxyl radical and hydrogen peroxide), endothelium-derived nitric oxide and cyclooxygenase mediators are involved in the regulation of vascular smooth muscle tone. An imbalance of these mediators can have profound implications in various cardiovascular disorders. Involvement of endogenous reactive oxygen species, endothelium-derived nitric oxide (NO) and cyclooxygenase mediators in 5-hydroxytryptamine- (5-HT-) induced contractions of endothelium intact rat aortic rings have been investigated in the present study. The contribution of each of the endogenous reactive oxygen species in mediating 5-HT-induced contractions was studied by pretreating the rings with their respective scavengers. Pretreatment of the rings with superoxide dismutase (superoxide radical scavenger), catalase (H (2)O (2)inactivator), mannitol (extracellular OH. scavenger), or thiourea (intracellular OH. radical scavenger) significantly depressed the 5-HT-induced contractions in the aortic rings. The responses to 5-HT in the presence of SOD or catalase were augmented byL -NAME pretreatment. Though aminotriazole partially inhibited the catalase activity, it inhibited 5-HT-induced contractions significantly. The results obtained thus suggest that endogenous generation of ROS (O(2).(-), H (2)O (2)and OH.) modulates 5-HT-induced rat aortic ring contractions. In addition, H (2)O (2)generated in the endothelium seems to regulate the vascular response and also act as a mediator to release other vasoactive substances. Basal production of NO by the endothelium seems to affect the vascular response due to its interaction with ROS mediators.
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PMID:Role of endogenous reactive oxygen derived species and cyclooxygenase mediators in 5-hydroxytryptamine-induced contractions in rat aorta: relationship to nitric oxide. 1212 25

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