Inhibition of inducible nitric oxide synthase reduces renal ischemia/reperfusion injury

Chatterjee, Prabal K.; Patel, Nimesh S. A.; Kvale, Espen Ø.; Cuzzocrea, Salvatore; Brown, Paul A.J.; Stewart, Keith Nicol; Mota-Filipe, Hélder; Thiemermann, Christoph

doi:10.1046/j.1523-1755.2002.00234.x

Cited by 229 publications

(185 citation statements)

References 45 publications

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“…The plasma levels of nitrite (used as an indicator of NO formation) measured at the end of the 6-h reperfusion period indicate I/R-induced elevated NO production as demonstrated previously (10). This elevated NO has been proposed to account, in part, for the proinflammatory processes that occurs within the kidney and contribute to acute renal failure (9) and due in part to the generation of peroxynitrite. The reduction of nitration of proteins after application of nitrite indicates that this treatment results in a reduction in peroxynitrite formation, and it is likely that this, in part, is responsible for the beneficial effects of nitrite treatment.…”

Section: Discussionmentioning

confidence: 55%

Nitrite-Derived Nitric Oxide Protects the Rat Kidney against Ischemia/Reperfusion Injury In Vivo

Tripatara¹,

Patel²,

Webb³

et al. 2007

Journal of the American Society of Nephrology

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213

159

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In normal conditions, nitric oxide (NO) is oxidized to the anion nitrite, but in hypoxia, this nitrite may be reduced back to NO by the nitrite reductase action of deoxygenated hemoglobin, acidic disproportionation, or xanthine oxidoreductase (XOR). Herein, is investigated the effects of topical sodium nitrite administration in a rat model of renal ischemia/reperfusion (I/R) injury. Rats were subjected to 60 min of bilateral renal ischemia and 6 h of reperfusion in the absence or presence of sodium nitrite (30 nmol) administered topically 1 min before reperfusion. Serum creatinine, serum aspartate aminotransferase, creatinine clearance, fractional excretion of Na ؉ , and plasma nitrite/nitrate concentrations were measured. The nitrite-derived NO-generating capacity of renal tissue was determined under acidic and hypoxic conditions by ozone chemiluminescence in homogenates of kidneys that were subjected to sham, ischemia-only, and I/R conditions. Nitrite significantly attenuated renal dysfunction and injury, an effect that was abolished by previous treatment of rats with the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazole-1-oxyl-3-oxide (2.5 mol intravenously 5 min before ischemia and 50 nmol topically 6 min before reperfusion). Renal tissue homogenates produced significant amounts of NO from nitrite, an effect that was attenuated significantly by the xanthine oxidoreductase inhibitor allopurinol. Taken together, these findings demonstrate that topically administered sodium nitrite protects the rat kidney against I/R injury and dysfunction in vivo via the generation, in part, of xanthine oxidoreductase-catalyzed NO production. These observations suggest that nitrite therapy might prove beneficial in protecting kidney function and integrity during periods of I/R such as those encountered in renal transplantation. U ntil recently, the nitrite anion was regarded merely as an inactive metabolite of nitric oxide (NO) oxidation produced under normal physiologic conditions, accounting for approximately 70% of the endogenous nitrite pool (1). However, we (2) and others (3) recently demonstrated that, far from being inactive, nitrite has marked protective effects in ischemia/reperfusion (I/R) injury of both the heart and the liver. Moreover, these studies demonstrate that the beneficial effects of nitrite are related to its reduction to NO, under ischemic conditions. J Am Soc NephrolThe generation of NO is attributed conventionally to the enzyme NO synthase (NOS), of which there are three isoforms. Endothelial NOS (eNOS)-derived NO plays an important role in determining and maintaining aspects of normal renal function, for instance proximal tubule sodium reabsorption (4,5), but in elevated concentrations, NO also contributes to renal pathophysiology (6), such as in proximal tubule ischemic injury (4). This dual nature of NO perhaps is an oversimplification, because NO either ameliorates or exacerbates renal injury, depending on the site and the rate of NO production and the chemical fate of NO (7,8). Further...

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Section: Discussionmentioning

confidence: 55%

Nitrite-Derived Nitric Oxide Protects the Rat Kidney against Ischemia/Reperfusion Injury In Vivo

Tripatara¹,

Patel²,

Webb³

et al. 2007

Journal of the American Society of Nephrology

Self Cite

213

159

View full text Add to dashboard Cite

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“…Indeed, treatment with inhibitors of iNOS has been repeatedly shown to have a dramatic beneficial effect in models of autoimmunity (36) or in clinical settings such as transplantation (37,38). We are currently engaged in the process of identifying nitrated proteins at sites of inflammation associated with autoimmune disease to assess whether these proteins constitute targets of the cellular immune response.…”

Section: Resultsmentioning

confidence: 99%

Cutting Edge: MHC Class II-Restricted Peptides Containing the Inflammation-Associated Marker 3-Nitrotyrosine Evade Central Tolerance and Elicit a Robust Cell-Mediated Immune Response

Birnboim

Lemay

Lam

et al. 2003

The Journal of Immunology

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Nitrotyrosine is widely recognized as a surrogate marker of up-regulated inducible NO synthase expression at sites of inflammation. However, the potential immunogenicity of autologous proteins containing nitrotyrosine has not previously been investigated. Herein, we used the I-EK-restricted T cell epitope of pigeon/moth cytochrome c (PCC/MCC88–103) to assess the ability of T cells to recognize ligands containing nitrotyrosine. Substitution of the single tyrosine (Y97) in PCC/MCC88–103 with nitrotyrosine abrogates recognition by the MCC88–103-specific T cell hybridoma 2B4. CBA (H2K) mice immunized with MCC88–103 or nitrated MCC88–103 peptides produce T cell responses that are mutually exclusive. Transgenic mice that constitutively express PCC under the control of an MHC class I promoter are tolerant toward immunization with MCC88–103, but exhibited a robust immune response against nitrated MCC88–103. Analysis of T cell hybridomas specific for nitrated-MCC88–103 indicated that subtle differences in TCR VDJ gene usage are sufficient to allow nitrotyrosine-specific T cells to escape the processes of central tolerance.

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“…Longitudinal in vivo studies are necessary to confirm this possibility. Nitric oxide production is significantly affected by the stimulation of ischemia/reperfusion in several tissues, such as the heart [41], skeletal muscle [42] and kidney [43]. Thus, constant nitric oxide production in the human placenta during labor may be characteristic of the human placenta.…”

Section: Discussionmentioning

confidence: 99%

Expression of Nitric Oxide Synthase Isoforms in the Human Placenta Is Not Altered by Labor

et al. 2003

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Abstract. Nitric oxide has various biological activities including smooth muscle relaxation, anti-inflammatory activity, anti-coagulatory activity. As the human placenta is known to express nitric oxide synthases, this study investigated the possible effect of labor on the expression of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) in human placental tissues at term. Both eNOS and iNOS mRNA expression in placental tissues in labor were significantly higher than those in the amnion, chorion laeve, decidua vera and myometrium. The eNOS mRNA and protein expressions in placental tissues in labor (n = 12) were 1.6023 ± 0.1652 (eNOS/GAPDH, mean ± SEM) and 12.8 ± 1.3 arbitrary units (AU), respectively, which were similar to those not in labor (n = 10), 1.5806 ± 0.2042 (eNOS/GAPDH) and 11.4 ± 1.8 AU. The iNOS mRNA and protein expressions in the placental tissues in labor were 1.2831 ± 0.2436 (iNOS/GAPDH) and 10.7 ± 2.1 AU respectively, similar to those not in labor, 1.9254 ± 0.8004 (iNOS/GAPDH) and 13.3 ± 1.8 AU. The guanosine 3',5'-cyclic monophosphate (cGMP) cocentration in the placental tissues in labor was 23.6 ± 1.4 fmol/g wet tissue, similar to that not in labor, 26.1 ± 2.0 fmol/g wet tissue. These findings suggest that nitric oxide production in the human placenta is maintained during labor.

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Inhibition of inducible nitric oxide synthase reduces renal ischemia/reperfusion injury

Cited by 229 publications

References 45 publications

Nitrite-Derived Nitric Oxide Protects the Rat Kidney against Ischemia/Reperfusion Injury In Vivo

Nitrite-Derived Nitric Oxide Protects the Rat Kidney against Ischemia/Reperfusion Injury In Vivo

Cutting Edge: MHC Class II-Restricted Peptides Containing the Inflammation-Associated Marker 3-Nitrotyrosine Evade Central Tolerance and Elicit a Robust Cell-Mediated Immune Response

Expression of Nitric Oxide Synthase Isoforms in the Human Placenta Is Not Altered by Labor

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