Nitric oxide and prostanoids protect the renal outer medulla from radiocontrast toxicity in the rat.

Agmon, Yoram; Peleg, Hagit; Greenfeld, Ziv; Rosen, Seymour; Brezis, Mayer

doi:10.1172/jci117421

Cited by 322 publications

(257 citation statements)

References 46 publications

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“…In rats, the inhibition of prostaglandin or NO synthesis was found to blunt the increase in outer medullary blood flow induced by radiocontrast and to aggravate regional hypoxia (7,25). Similarly, as reviewed elsewhere (41), altered protective mechanisms bring about the susceptibility to develop CIN in high-risk patients.…”

Section: Risk Factors For Cin Predispose To Medullary Oxygen Insufficmentioning

confidence: 76%

“…This group of researchers (24) noted a similar decline in outer medullary regional blood flow, using both laser Doppler needle probes and hydrogen washout techniques; however, at very high volumes of injected radiocontrast, outer medullary regional microcirculation markedly increased (25)(26)(27), as long as NO or prostaglandin synthesis remained intact (25). Thus, so far, the impact of radiocontrast on outer medullary perfusion remains a matter of debate, with the different patterns of response possibly related to the type, volume, and route of administration of the dye.…”

Section: Radiocontrast-induced Decrease In Renal Oxygen Supplymentioning

confidence: 85%

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Renal Parenchymal Hypoxia, Hypoxia Adaptation, and the Pathogenesis of Radiocontrast Nephropathy

Heyman¹,

Rosen²,

Rosenberger³

2008

Clinical Journal of the American Society of Nephrology

209

164

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Background and objectives: Renal parenchymal PO 2 declines after the administration of iodinated radiocontrast agents, reaching critically low levels of approximately 10 mmHg in medullary structures.Design, setting, participants, & measurements: In this review, the causes of renal parenchymal hypoxia and its potential role in the pathogenesis of contrast nephropathy are appraised.Results: Commonly associated predisposing factors are associated with a propensity to enhance renal hypoxia. Indeed, animal models of radiocontrast nephropathy require the induction of such predisposing factors, mimicking clinical scenarios that lead to contrast nephropathy in high-risk individuals. In these models, in association with medullary hypoxic damage, a transient local cellular hypoxia response is noted, initiated at least in part by hypoxia-inducible factors. Some predisposing conditions that are distinguished by chronically aggravated medullary hypoxia, such as tubulointerstitial disease and diabetes, are characterized by a priori upregulation of hypoxia-inducible factors, which seems to confer tolerance against radiocontrastrelated hypoxic tubular damage. Renal dysfunction under such circumstances likely reflects to some extent altered intrarenal hemodynamics, rather than acute tubular injury.Conclusions: Real-time, noninvasive novel methods may help to differentiate between evolving tubular damage and altered hemodynamics and in the design of appropriate preventive interventions.

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Section: Risk Factors For Cin Predispose To Medullary Oxygen Insufficmentioning

confidence: 76%

Section: Radiocontrast-induced Decrease In Renal Oxygen Supplymentioning

confidence: 85%

Renal Parenchymal Hypoxia, Hypoxia Adaptation, and the Pathogenesis of Radiocontrast Nephropathy

Heyman¹,

Rosen²,

Rosenberger³

2008

Clinical Journal of the American Society of Nephrology

209

164

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“…16 Decrease in NO production, a potent vasodilator, has also been shown and suggested as one of the underlying mechanisms contributing to vasoconstriction and CIN pathophysiology. 17,18 Because direct renal tubular damage caused by reactive oxygen species has been confirmed to play a role in CIN pathogenesis by many studies, 19,20 many agents with antioxidative properties have been evaluated for avoidance of kidney injury.…”

Section: Discussionmentioning

confidence: 99%

Does Nebivolol Prevent Contrast‐Induced Nephropathy in Humans?

Günebakmaz

Kaya

Koç

et al. 2012

Clinical Cardiology

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Background:An experimental study showed that nebivolol is an effective agent in contrast‐induced nephropathy (CIN) prophylaxis.Hypothesis:We hypothesized that prophylactic nebivolol use had protective effects on renal function in human beings subjected to iodinated contrast agent since it has vasodilatory effect and antioxidant properties.Methods:The present study enrolled 120 patients scheduled for coronary angiography and ventriculography. All patients were hydrated with intravenous isotonic saline. The patients in group I received 600 mg N‐acetylcysteine every 12 hours for 4 days. The patients in group II received 5 mg nebivolol every 24 hours for 4 days. The patients in group III were only hydrated. The primary endpoint was the occurrence of CIN. The secondary endpoint was the change in serum creatinine (Cr) levels at 2 days and 5 days after the contrast exposure.Results:Nine (22.5%) patients in group I developed CIN, as did 8 patients (20.0%) in group II and 11 patients (27.5%) in group III (P = 0.72). Changes in mean Cr level from baseline to day 2 were not statistically significant in all groups. However, we detected a statistically significant increase in mean Cr levels at day 5 compared with baseline levels in group I and group III (from 1.42 ± 0.13 to 1.52 ± 0.26, p2 = 0.02; and from 1.43 ± 0.14 to 1.55 ± 0.30, p2 = 0.01, respectively). Although an increase was detected in mean Cr level from baseline to the 5‐day Cr level in group II, this did not reach statistical significance (from 1.40 ± 0.12 to 1.48 ± 0.23, P = 0.06).Conclusions:Pretreatment with nebivolol is protective against nephrotoxic effects of contrast media. © 2012 Wiley Periodicals, Inc.The authors have no funding, financial relationships, or conflicts of interest to disclose.

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“…In the kidney, nNOS is expressed in cells of the macula densa and seems to participate in tubuloglomerular feedback, but has minimal effect on medullary perfusion (51,52), in contrast to eNOS (53). NOS inhibitors have been shown to induce hypoxic medullary damage in models of renal ischemia, highlighting the role of NO in maintaining regional renal blood flow under these conditions (54). Despite having a common end product (NO), activating different types of NOS can have very different effects on renal tissue, depending on both the temporal profile and topography of NO production by each NOS enzyme (42).…”

Section: Microvascular Dysfunction and The Balance Between Vasoconstrmentioning

confidence: 99%

“…Conversely, infusing nonselective NOS inhibitors that block eNOS activity has been shown to worsen both cortical and medullary blood flow and oxygenation (45,62). Indeed, eNOS-derived NO may act in a paracrine fashion, affecting surrounding cells and preventing vascular dysfunction by inhibiting platelet aggregation and preventing leukocyte activation (63), as well as having a direct vasodilatory effect (54). The inability of hypoxic endothelial cells to produce NO could thus have detrimental effects and participate in renal damage (64).…”

Section: Microvascular Dysfunction and The Balance Between Vasoconstrmentioning

confidence: 99%

Renal Hypoxia and Dysoxia After Reperfusion of the Ischemic Kidney

Legrand

Mik

Johannes³

et al. 2008

Mol Med

237

169

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Ischemia is the most common cause of acute renal failure. Ischemic-induced renal tissue hypoxia is thought to be a major component in the development of acute renal failure in promoting the initial tubular damage. Renal oxygenation originates from a balance between oxygen supply and consumption. Recent investigations have provided new insights into alterations in oxygenation pathways in the ischemic kidney. These findings have identified a central role of microvascular dysfunction related to an imbalance between vasoconstrictors and vasodilators, endothelial damage and endothelium-leukocyte interactions, leading to decreased renal oxygen supply. Reduced microcirculatory oxygen supply may be associated with altered cellular oxygen consumption (dysoxia), because of mitochondrial dysfunction and activity of alternative oxygen-consuming pathways. Alterations in oxygen utilization and/or supply might therefore contribute to the occurrence of organ dysfunction. This view places oxygen pathways' alterations as a potential central player in the pathogenesis of acute kidney injury. Both in regulation of oxygen supply and consumption, nitric oxide seems to play a pivotal role. Furthermore, recent studies suggest that, following acute ischemic renal injury, persistent tissue hypoxia contributes to the development of chronic renal dysfunction. Adaptative mechanisms to renal hypoxia may be ineffective in more severe cases and lead to the development of chronic renal failure following ischemia-reperfusion. This paper is aimed at reviewing the current insights into oxygen transport pathways, from oxygen supply to oxygen consumption in the kidney and from the adaptation mechanisms to renal hypoxia. Their role in the development of ischemia-induced renal damage and ischemic acute renal failure are discussed.

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Nitric oxide and prostanoids protect the renal outer medulla from radiocontrast toxicity in the rat.

Cited by 322 publications

References 46 publications

Renal Parenchymal Hypoxia, Hypoxia Adaptation, and the Pathogenesis of Radiocontrast Nephropathy

Renal Parenchymal Hypoxia, Hypoxia Adaptation, and the Pathogenesis of Radiocontrast Nephropathy

Does Nebivolol Prevent Contrast‐Induced Nephropathy in Humans?

Renal Hypoxia and Dysoxia After Reperfusion of the Ischemic Kidney

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