GW274150, a potent and highly selective inhibitor of iNOS, reduces experimental renal ischemia/reperfusion injury

Chatterjee, Prabal K.; Patel, Nimesh S. A.; Sivarajah, Ahila; Kvale, Espen Ø.; Dugo, Laura; Cuzzocrea, Salvatore; Brown, Paul A.J.; Stewart, Keith Nicol; Mota-Filipe, Hélder; Britti, Domenico; Yaqoob, Muhammad; Thiemermann, Christoph

doi:10.1046/j.1523-1755.2003.00802.x

Cited by 132 publications

(163 citation statements)

References 54 publications

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“…The protective effects of NO seem to be associated with eNOS-derived NO, which causes vasodilation and inhibits leukocyte adhesion and platelet aggregation (31), whereas the damaging and proinflammatory effects have been associated with iNOS-derived NO, which forms the peroxynitrite anion from the interaction of NO and superoxide (32). 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.…”

Section: Discussionmentioning

confidence: 64%

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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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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: 64%

“…Tyrosine nitration was detected in kidney sections by immunohistochemistry, as described previously (10).…”

Section: Immunohistochemical Localization Of Nitrotyrosinementioning

confidence: 99%

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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“…According to the report by Chatterjee et al (5), nitrite production in the primary culture of human proximal tubule cells was Ͻ5 nmol⅐mg protein Ϫ1 ⅐24 h Ϫ1 under the basal condition, whereas it exhibited a 10-fold increase after treatment with cytokines. They also demonstrated that the plasma level of nitrite/nitrate significantly increased in rats subjected to bilateral renal ischemia (6). Therefore, immune-inflammatory responses or some tissue damage might be involved in the NO-mediated modulation of K ϩ channel activity.…”

Section: Discussionmentioning

confidence: 95%

Regulation of an inwardly rectifying K⁺channel by nitric oxide in cultured human proximal tubule cells

Nakamura¹,

Hirano²,

Kubokawa³

2004

American Journal of Physiology-Renal Physiology

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“…2). Although AST and LDH are not kidney-specific organ injury markers, they have been commonly used for indicating the severity of cellular injury in the kidney after IR (10)(11)(12). These findings correlated with the visible changes that renal IRI caused on histopathologic examination.…”

Section: Wnt Agonist Decreases Renal Tissue Injurymentioning

confidence: 92%

Wnt Agonist Decreases Tissue Damage and Improves Renal Function After Ischemia-Reperfusion

Kuncewitch

Yang

Nicastro

et al. 2013

Journal of Surgical Research

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GW274150, a potent and highly selective inhibitor of iNOS, reduces experimental renal ischemia/reperfusion injury

Cited by 132 publications

References 54 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

Regulation of an inwardly rectifying K⁺channel by nitric oxide in cultured human proximal tubule cells

Wnt Agonist Decreases Tissue Damage and Improves Renal Function After Ischemia-Reperfusion

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GW274150, a potent and highly selective inhibitor of iNOS, reduces experimental renal ischemia/reperfusion injury

Cited by 132 publications

References 54 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

Regulation of an inwardly rectifying K+channel by nitric oxide in cultured human proximal tubule cells

Wnt Agonist Decreases Tissue Damage and Improves Renal Function After Ischemia-Reperfusion

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Regulation of an inwardly rectifying K⁺channel by nitric oxide in cultured human proximal tubule cells