Effects of sodium nitrite on ischemia-reperfusion injury in the rat kidney

Basireddy, Mahesh; Isbell, T. Scott; Teng, Xinjun; Patel, Rakesh P.; Agarwal, Anupam

doi:10.1152/ajprenal.00334.2005

Cited by 66 publications

(53 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is interesting that whereas topical nitrite administration was of clear benefit, intravenous administration of nitrite had no effect on the renal dysfunction and injury that were caused by the I/R insult, confirming the recent study of Basireddy et al (23). Because the concentration of nitrite that was used in this study was the same for both routes (60 mol/L, identical to that of Basireddy et al) and the timing of nitrite application at 1 min before reperfusion (i.e., 59 min in to the ischemic event) was the same in both protocols, it is likely that the route of administration underlies the difference in efficacy.…”

Section: Discussionsupporting

confidence: 79%

See 1 more Smart Citation

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

212

159

View full text Add to dashboard Cite

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...

show abstract

Section: Discussionsupporting

confidence: 79%

“…There is evidence that the systemic administration of nitrite does not reduce renal I/R in the rat (23). However, we investigated whether direct topical application of sodium nitrite to the renal surface in vivo reduces renal dysfunction, injury, and inflammation in a rat model of I/R injury.…”

mentioning

confidence: 97%

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

212

159

View full text Add to dashboard Cite

show abstract

“…This concept has led to studies testing nitrite as a direct NO donor in experimental ischemia models, such as hypoxiainduced pulmonary vasoconstriction, 18 hemorrhagic stroke, 19 hepatic and cardiac I/R injury, 13 and renal I/R injury. 20 Nitrite exerted profound dose-dependent protective effects against hepatic and myocardial I/R, although it did not provide protection in renal I/R injury, suggesting a unique metabolism of nitrite in each tissue. 15,20 Cerebral ischemia also decreases the extracellular pH and oxygen level in the brain.…”

Section: Discussionmentioning

confidence: 95%

“…20 Nitrite exerted profound dose-dependent protective effects against hepatic and myocardial I/R, although it did not provide protection in renal I/R injury, suggesting a unique metabolism of nitrite in each tissue. 15,20 Cerebral ischemia also decreases the extracellular pH and oxygen level in the brain. Therefore, NO can be generated efficiently in the ischemic brain by direct reduction of nitrite.…”

Section: Discussionmentioning

confidence: 95%

Early Intravenous Infusion of Sodium Nitrite Protects Brain Against In Vivo Ischemia-Reperfusion Injury

Jung

Chu

et al. 2006

Stroke

231

202

View full text Add to dashboard Cite

Background and Purpose-The rate of nitric oxide (NO) generation from nitrite is linearly dependent on reductions in oxygen and pH levels. Recently, nitrite-derived NO has been reported to exert a profound protection against liver and heart ischemia-reperfusion injury. In this study, we hypothesized that nitrite would be reduced to NO in the ischemic brain and exert NO-dependent neuroprotective effects. Methods-Cerebral ischemia-reperfusion injury was induced by intraluminal thread occlusion of middle cerebral artery in the adult male rats. Solutions of sodium nitrite were infused intravenously at the time of reperfusion. Sodium nitrate and carboxy-PTIO (30 minutes before ischemic surgery), a direct NO scavenger, were infused for comparisons. Results-Nitrite reduced infarction volume and enhanced local cerebral blood flow and functional recovery. The effects were observed at concentrations of 48 nmol and 480 nmol, but not at 4800 nmol nitrite and 480 nmol nitrate. The neuroprotective effects of nitrite were inhibited completely by the carboxy-PTIO. The 480 nmol nitrite attenuated dihydroethidium activity, 3-nitrotyrosine formation, and lipid peroxidation in the ischemic brain. Conclusions-Nitrite exerted profound neuroprotective effects with antioxidant properties in the ischemic brains. These results suggest that nitrite, as a biological storage reserve of NO, may be a novel therapeutic agent in the setting of acute stroke.

show abstract

“…In experimental settings, intravenously administered sodium nitrite has been reported to protect against ischemia-reperfusion injury in the heart and liver (Duranski et al, 2005) but not the kidney (Basireddy et al, 2006), and was recently described as a neuroprotectant (Jung et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Nitrite Does Not Provide Additional Protection to Thrombolysis in a Rat Model of Stroke with Delayed Reperfusion

Schatlo

Henning

Pluta

et al. 2007

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

An adjuvant therapy to prolong the therapeutic window for stroke patients is urgently needed. This randomized, blinded, placebo-controlled study investigated adjuvant intravenous sodium nitrite with recombinant tissue plasminogen activator (rtPA) in middle cerebral artery occlusion (MCAO) with 6 and 2 h of ischemia followed by reperfusion in Sprague-Dawley rats (n = 59). Quantitative diffusion, T 1 -, T 2 -weighted, and semiquantitative perfusion imaging were performed before and after reperfusion and at 48 h after ischemia to determine the spatiotemporal evolution of stroke. After 48 h animals were killed and examined to evaluate infarct size and evidence of hemorrhagic transformation. Factor VIII immunostaining was performed to assess vessel morphology. Nitrite treatment (6 h group: 37.5 lmol for more than 90 mins; 2 h group: 26.25 and 1.75 lmol for more than 60 mins) did not reduce infarct volume 48 h after MCAO compared with saline-treated placebo groups after 6 or 2 h of MCAO. Stroke progression from baseline to 48 h, based on the apparent diffusion coefficient and relative cerebral blood flow deficits before and after reperfusion and T 2 -weighted hyperintensity at 48 h, did not differ between treated and control animals. These results suggest that nitrite is not a protective adjuvant therapy to delayed rtPA administration after ischemic stroke in rats.

show abstract

Effects of sodium nitrite on ischemia-reperfusion injury in the rat kidney

Cited by 66 publications

References 56 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

Early Intravenous Infusion of Sodium Nitrite Protects Brain Against In Vivo Ischemia-Reperfusion Injury

Nitrite Does Not Provide Additional Protection to Thrombolysis in a Rat Model of Stroke with Delayed Reperfusion

Contact Info

Product

Resources

About