Possible role for oxygen free radicals in the regulation of renal nitric oxide synthesis and blood flow

Myers, Stuart I.; Hernandez, R.; Castaneda, Antonio A.

doi:10.1016/s0002-9610(99)80230-x

Cited by 28 publications

(15 citation statements)

References 19 publications

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“…Blocking neutrophil adhesion to vascular endothelium is an important step in preventing local release of activated neutrophil oxidants that may damage either the tissue directly or serve to downregulate endothelial prostaglandin I 2 or NO synthesis. Release of superoxide radicals by activated neutrophils was shown to decrease biologically active NO, an event prevented by treatment with superoxide dismutase or L-ARG [28]. Some NO donors may also act as a neuroprotective agent through downregulation of Nmethyl-D-aspartate receptor activity in the brain [29].…”

Section: Discussionmentioning

confidence: 99%

Role of Nitric Oxide in Hypoxia-Induced Changes in Newborn Rats

Kılıç

Kiliç²,

Güven³

et al. 2000

Neonatology

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In order to investigate the role of nitric oxide (NO) in hypoxic tissue damage in newborns, we studied the effects of systemic administration of an inhibitor of NO synthase, N^G-nitro-L-arginine (L-NNA), and the precursor for the synthesis of NO, L-arginine (L-ARG), on the biochemical and histological changes in brain, heart, lung, liver, kidney, intestine, and skeletal muscle tissues. Four groups of 1-day-old Wistar rat pups were used: control, hypoxic, L-ARG, and L-NNA groups. L-ARG 100 mg/kg or L-NNA 2 mg/kg was administered as a bolus intraperitoneally 1.5 h before hypoxia. Hypoxia increased lipid peroxidation in all tissues except muscle; this increase was prevented by L-NNA and L-ARG in brain, heart, lung, kidney, and liver tissues. L-NNA in intestine and L-ARG in muscle tissue increased lipid peroxidation. The tissue-associated myeloperoxidase activity was decreased in the liver by L-NNA and L-ARG. Histopathological changes in intestines were villous epithelial separation and hyperemia in hypoxic and L-NNA groups which were not observed in control and L-ARG groups. In lungs, pulmonary hemorrhage was observed only in the hypoxic group. These data suggest that NO acts both as a destructive and a protective agent in the pathogenesis of hypoxia-reoxygenation injuries.

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Section: Discussionmentioning

confidence: 99%

Role of Nitric Oxide in Hypoxia-Induced Changes in Newborn Rats

Kılıç

Kiliç²,

Güven³

et al. 2000

Neonatology

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“…Increased ROS activity is also suspected as an important factor in the progression of renal disease and, in particular, nephrosclerosis (Gonick et al, 1996;Shah, 1989). In addition, increased ROS can contribute to associated renal injury by inactivating nitric oxide (NO) (Bosse and Bachmann, 1997;Heeringa et al, 1998;MacMillan-Crow et al, 1996;Myers et al, 1995;Vaziri et al, 1999b). It has been suggested that NO deficiency can cause a variety of renal injuries (Baylis et al, 1992;Fujihara et al, 1994;Ribeiro et al, 1992;Yamada et al, 1996).…”

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confidence: 99%

Association of Renal Injury with Increased Oxygen Free Radical Activity and Altered Nitric Oxide Metabolism in Chronic Experimental Hemosiderosis

Zhou

Lászik

Wang

et al. 2000

Laboratory Investigation

126

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SUMMARY:Chronic iron (Fe) overload is associated with a marked increase in renal tissue iron content and injury. It is estimated that 10% of the American population carry the gene for hemochromatosis and 1% actually suffer from iron overload. The mechanism of iron overload-associated renal damage has not been fully elucidated. Iron can accelerate lipid peroxidation leading to organelle membrane dysfunction and subsequent cell injury/death. Iron-catalyzed generation of reactive oxygen species (ROS) is responsible for initiating the peroxidatic reaction. We investigated the possible association of oxidative stress and its impact on nitric oxide (NO) metabolism in iron-overload-associated renal injury. Rats were randomized into Fe-loaded (given 0.5 g elemental iron/kg body weight as iron dextran; IV), Fe-depleted (given an iron-free diet for 20 weeks), and control groups. Renal histology, tissue expression of endothelial and inducible nitric oxide synthases (eNOS and iNOS), renal tissue expression of nitrotyrosine, plasma, and renal tissue lipid peroxidation product, malondialdehyde (MDA), and plasma and urinary NO metabolites (NOx) were examined. Iron overload was associated with mild proteinuria, tissue iron deposition together with significant glomerulosclerosis, tubular atrophy, and interstitial fibrosis. Rare focal glomerulosclerosis and tubulointerstitial changes were noted in normal controls. No renal lesions were observed in Fe-depleted rats. Iron deposits were seen in glomeruli, proximal tubules, and interstitium. The iron staining in the distal tubules was negligible. Both plasma and renal tissue MDA and renal tissue nitrotyrosine were increased significantly in Fe-loaded rats compared with control rats. In contrast, Fe-depleted animals showed a marked reduction in plasma and renal tissue MDA and nitrotyrosine together with significant elevation of urinary NOx excretion. In addition, iron-overload was associated with up-regulation of renal eNOS and iNOS expressions when compared with the control and Fe-depleted rats that showed comparable values. In conclusion, chronic iron overload resulted in iron deposition in the glomeruli and proximal tubules with various renal lesions and evidence of increased ROS activity, enhanced ROS-mediated inactivation, and sequestration of NO and compensatory up-regulation of renal eNOS and iNOS expressions. However, iron depletion was associated with reduced MDA and tissue nitrotyrosine abundance, increased urinary NOx excretion, normal nitric oxide synthase (NOS) expression, and absence of renal injury. These findings point to the possible role of ROS in chronic iron overload-induced renal injury. (Lab Invest 2000, 80:1905-1914.

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“…It is known that NO donors such as isosorbide dinitrate, sodium nitroprusside, nitroglycerin, L -arginine and MS create NO-related effects in the vascular system, especially vasodilator effect in arteries [31][32][33] . However, in the reoxygenation phase, the interaction between NO and ؒ O 2 product, peroxynitrite anion (ONOO -), is a potent oxidant that has reactivity similar to the -OH radical.…”

Section: Discussionmentioning

confidence: 99%

The Effects of Nitric Oxide Donor Molsidomine on Skeletal Muscle Damage in a Rat Hind Limb Model of Ischemia-Reperfusion

Öztürk

Özyurt²,

Somay³

et al. 2008

Eur Surg Res

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Background: In this experimental study, we aimed to examine the protective effect of molsidomine (MS), a nitric oxide (NO) donor, against ischemia-reperfusion (I-R) injury in a rat skeletal muscle model. Methods: Ischemia was achieved by application of an elastic rubber band as high as possible on the left thigh of the rats. Group 1: the control group received a sham operation. Group 2: the I-R group received I-R injury to the left hind limbs. Group 3: the I-R/MS group underwent the same model of I-R injury and received MS. Group 4: the I-R/L-NAME (N-ω-nitro-L-arginine-methyl ester) group underwent the same model of I-R injury and received L-NAME, an inhibitor of NO synthase. Results: In groups 2 and 4, malondialdehyde increased significantly when compared to groups 1 and 3. Superoxide dismutase, catalase and glutathione peroxidase increased significantly in group 3 compared to groups 2 and 4. The NO levels were significantly elevated in group 3 compared to groups 2 and 4. In addition, the histopathological score was considerably lower in group 3 than in group 4. The number of necrotic muscle fibers and infiltration of neutrophils were significantly reduced in the MS-treated group. Conclusions: These findings suggest that MS can exert a protective effect against skeletal muscle injury caused by I-R in the rats.

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Possible role for oxygen free radicals in the regulation of renal nitric oxide synthesis and blood flow

Cited by 28 publications

References 19 publications

Role of Nitric Oxide in Hypoxia-Induced Changes in Newborn Rats

Role of Nitric Oxide in Hypoxia-Induced Changes in Newborn Rats

Association of Renal Injury with Increased Oxygen Free Radical Activity and Altered Nitric Oxide Metabolism in Chronic Experimental Hemosiderosis

The Effects of Nitric Oxide Donor Molsidomine on Skeletal Muscle Damage in a Rat Hind Limb Model of Ischemia-Reperfusion

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