The Use of the Endothelin Receptor Antagonist, Tezosentan, Before or After Renal Ischemia Protects Renal Function1

Sm, Wilhelm; Nt, Stowe; Av, Robinson; Ja, Schulak

doi:10.1097/00007890-200101270-00007

Cited by 53 publications

(30 citation statements)

References 18 publications

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“…In immunohistochemical study to determine the localization of ET-1 peptide in the postischemic kidney, an enhanced staining pattern was observed in necrotic tubular cells more markedly in NCX1 ϩ/ϩ mice than in NCX1 ϩ/Ϫ mice. When the present study was in progress, similar localization pattern of ET-1 peptide in the kidney after the ischemia and 24 h of reperfusion was demonstrated by Wilhelm et al (2001). Previously, Wilhelm et al (1999) demonstrated increased ET-1 expression in the peritubular capillary network of the kidney after ischemia.…”

Section: Acute Renal Failure and Nasupporting

confidence: 83%

Attenuation of Ischemia/Reperfusion-Induced Renal Injury in Mice Deficient in Na⁺/Ca²⁺Exchanger

Yamashita

Kita²,

Iwamoto³

et al. 2003

J Pharmacol Exp Ther

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Using Naϩ /Ca 2ϩ exchanger (NCX1)-deficient mice, the pathophysiological role of Ca 2ϩ overload via the reverse mode of NCX1 in ischemia/reperfusion-induced renal injury was investigated. Because NCX1 Ϫ/Ϫ homozygous mice die of heart failure before birth, we used NCX1 ϩ/Ϫ heterozygous mice. NCX1 protein in the kidney of heterozygous mice decreased to about half of that of wild-type mice. Expression of NCX1 protein in the tubular epithelial cells and Ca 2ϩ influx via NCX1 in renal tubules were markedly attenuated in the heterozygous mice. Ischemia/ reperfusion-induced renal dysfunction in heterozygous mice was significantly attenuated compared with cases in wild-type mice. Histological renal damage such as tubular necrosis and proteinaceous casts in tubuli in heterozygous mice were much less than that in wild-type mice. Ca 2ϩ deposition in necrotic tubular epithelium was observed more markedly in wild-type than in heterozygous mice. Increases in renal endothelin-1 content were greater in wild-type than in heterozygous mice, and this reflected the difference in immunohistochemical endothelin-1 localization in necrotic tubular epithelium. When the preischemic treatment with KB-R7943 was performed, the renal functional parameters of both NCX1 ϩ/ϩ and NCX1 ϩ/Ϫ acute renal failure mice were improved to the same level. These findings strongly support the view that Ca 2ϩ overload via the reverse mode of Na ϩ /Ca 2ϩ exchange, followed by renal endothelin-1 overproduction, plays an important role in the pathogenesis of ischemia/reperfusion-induced renal injury.Renal ischemia is characterized by the depletion of ATP and the development of intracellular acidosis, which alter cellular ionic homeostasis. In particular, elevated intracellular Ca 2ϩ concentration causes cellular injury during ischemia and leads to irreversible renal damage during reperfusion (Schrier et al., 1987). An increase in the intracellular Na ϩ concentration has been shown to correlate with Ca 2ϩ

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Section: Acute Renal Failure and Nasupporting

confidence: 83%

Attenuation of Ischemia/Reperfusion-Induced Renal Injury in Mice Deficient in Na⁺/Ca²⁺Exchanger

Yamashita

Kita²,

Iwamoto³

et al. 2003

J Pharmacol Exp Ther

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“…One available evidence is that ET-1 is first expressed in increased quantities in the peritubular capillary network shortly after the onset of renal ischemia and then transported across the basement membrane of the adjacent tubular epithelial cell, which are then sloughed off during the development of acute tubular necrosis. 41) Since changes in renal ET-1 contents were parallel to those in renal venous NA levels, one might speculate that ET-1 overproduction in the post-ischemic kidney resulted from the enhanced NA release from renal sympathetic nerves. In a recent study, we found that ischemia/reperfusion-induced ARF was attenuated by a surgical or pharmacological blockade of renal sympathetic nerve, followed by a suppression of elevated renal venous NA levels.…”

Section: Discussionmentioning

confidence: 98%

Tempol Protects against Ischemic Acute Renal Failure by Inhibiting Renal Noradrenaline Overflow and Endothelin-1 Overproduction

Fujii

Takaoka

Ohkita

et al. 2005

Biological & Pharmaceutical Bulletin

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Ischemic acute renal failure (ARF) is a frequent clinical syndrome with high morbidity and mortality.1) Reperfusion of previously ischemic renal tissue initiates a complex cellular events that results in injury and the eventual death of renal cells due to a combination of apoptosis and necrosis.2)The molecular mechanisms underlying the ischemia/reperfusion-induced renal injury are poorly understood, but it has been reported that several causal factors (ATP depletion, reactive oxygen species, phospholipase activation, neutrophil infiltration, vasoactive peptides etc.) are contributive to the pathogenesis of this renal damage.3) Enhancement of renal sympathetic nerve activity and its consequent effect on noradrenaline (NA) overflow from the nerve endings has also been considered as one of the factors which cause the ischemia/reperfusion-induced renal injury. 4,5) In a recent study, we found that ischemia/reperfusion-induced ARF was attenuated by a surgical or pharmacological blockade of renal sympathetic nerve, followed by a suppression of elevated renal venous NA levels. 6) 4-Hydroxy-2,2,6,6-tetramethyl piperidinoxyl (tempol) is a membrane-permeable and metal-independent superoxide dismutase mimetic that has been shown to be specific for superoxide anion (O 2 Ϫ ). 7,8) Several studies have demonstrated that tempol could reduce the renal dysfunction and injury caused by ischemia/reperfusion, mainly through its free radical scavenging activity.9,10) It is accumulating evidence that oxidative stress is one of causal factors in developing various cardiovascular diseases and that antioxidative agents and substances can attenuate cardiovascular diseases such as hypertension and post-ischaemic organ damage. 11,12) In addition, recent studies have shown that tempol-induced reduction in O 2 Ϫ production leads to decreased activity of renal sympathetic nerve, which may be contributive to the hypotensive action of tempol. 13,14) These findings led us to evaluate the relationship between tempol-induced improvement on the postischemic ARF and renal sympathetic nervous system.In the present study, we investigated the effect of tempol treatment on ischemia/reperfusion-induced renal dysfunction, tissue injury and NA levels in renal venous plasma, which are elevated in the post-ischemic kidney and involved in the post-ischaemic ARF. [4][5][6] In addition, we examined the effect of tempol on renal endothelin-1 (ET-1) overproduction, which is a possible mediator of the pathogenesis of the postischaemic ARF. [15][16][17] MATERIALS AND METHODS Animals and Experimental DesignMale SpragueDawley rats (10 weeks of age, Japan SLC, Shizuoka, Japan) were used. Animals were housed in a light-controlled room with a 12 h light/dark cycle and were allowed ad libitum access to food and water. Experimental protocols and animal care methods in the experiments were approved by the Experimental Animal Committee at Osaka University of Pharmaceutical Sciences. Two weeks before the study (at 8 weeks of age), the right kidney was removed through a smal...

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“…This agent is a substrate for ET␣ receptors, found on Ito cells, and ET␤ receptors, found on endothelial cells and Kupffer cells. 107 In rats given tezosentan before reper- fusion, serum glutamic oxaloacetic transaminase release was significantly lower, and at 24 hours, histology was markedly improved over that of controls. There was also a reduction in chemokines (interleukin-1␤ and MIP-2) released from the Kupffer cells.…”

Section: Experimental Strategies For the Manipulation Of Marginal Donorsmentioning

confidence: 97%

“…There was also a reduction in chemokines (interleukin-1␤ and MIP-2) released from the Kupffer cells. 107 Soluble forms of the adhesion molecule receptor blockers prevent neutrophils and platelets from adhering to endothelial cell surface. Brain death increases sensitivity to IR injury and CIT and may contribute to immunogenicity.…”

Section: Experimental Strategies For the Manipulation Of Marginal Donorsmentioning

confidence: 99%

The utility of marginal donors in liver transplantation

Busuttil¹

2003

Liver Transplantation

628

508

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The shortage of organs has led centers to expand their criteria for the acceptance of marginal donors. The combination of multiple marginal factors seems to be additive on graft injury. In this review, the utility of various marginal donors in patients requiring liver transplantation will be described, including older donors, steatotic livers, non-heart-beating donors, donors with viral hepatitis, and donors with malignancies. The pathophysiology of the marginal donor will be discussed, along with strategies for minimizing the ischemia reperfusion injury experienced by these organs. Finally, new strategies for improving the function of the marginal/expanded donor liver will be reviewed. (Liver Transpl 2003;9:651-663.)

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The Use of the Endothelin Receptor Antagonist, Tezosentan, Before or After Renal Ischemia Protects Renal Function1

Cited by 53 publications

References 18 publications

Attenuation of Ischemia/Reperfusion-Induced Renal Injury in Mice Deficient in Na⁺/Ca²⁺Exchanger

Attenuation of Ischemia/Reperfusion-Induced Renal Injury in Mice Deficient in Na⁺/Ca²⁺Exchanger

Tempol Protects against Ischemic Acute Renal Failure by Inhibiting Renal Noradrenaline Overflow and Endothelin-1 Overproduction

The utility of marginal donors in liver transplantation

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The Use of the Endothelin Receptor Antagonist, Tezosentan, Before or After Renal Ischemia Protects Renal Function1

Cited by 53 publications

References 18 publications

Attenuation of Ischemia/Reperfusion-Induced Renal Injury in Mice Deficient in Na+/Ca2+Exchanger

Attenuation of Ischemia/Reperfusion-Induced Renal Injury in Mice Deficient in Na+/Ca2+Exchanger

Tempol Protects against Ischemic Acute Renal Failure by Inhibiting Renal Noradrenaline Overflow and Endothelin-1 Overproduction

The utility of marginal donors in liver transplantation

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Product

Resources

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Attenuation of Ischemia/Reperfusion-Induced Renal Injury in Mice Deficient in Na⁺/Ca²⁺Exchanger

Attenuation of Ischemia/Reperfusion-Induced Renal Injury in Mice Deficient in Na⁺/Ca²⁺Exchanger