The effect of endothelin antagonists on renal ischaemia-reperfusion injury and the development of acute renal failure in the rat

Huang, Chunlong; Huang, Chunhua; Hestin, D.; Dent, Paul C.; Barclay, Paul T.; Collis, Michael G.; Johns, Edward J.

doi:10.1093/ndt/17.9.1578

Cited by 26 publications

(19 citation statements)

References 15 publications

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“…Of all the vasoconstrictive agents, ET-1 seems to be particularly important, because its level increased after ischemia and blockage of the ET pathway by endothelin A receptor antagonists protects against renal IRI (12). In the present study, the expression of ET-1 in kidney was increased following IRI but was suppressed by IMD overexpression, likewise, through the antioxidative ability of IMD.…”

Section: Discussionsupporting

confidence: 51%

Intermedin protects against renal ischemia-reperfusion injury by inhibition of oxidative stress

Qiao

Liu

et al. 2013

American Journal of Physiology-Renal Physiology

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Reactive oxygen species (ROS) play a critical role in renal ischemia-reperfusion injury (IRI). Intermedin (IMD) reportedly protected against myocardial IRI via its antioxidant effects; however, its protective role in renal IRI has not been investigated. We overexpressed IMD in rat kidneys and examined how the kidneys respond to renal IRI. Eukaryotic expression plasmid encoding the rat IMD gene or control empty vector was transfected into the left kidney using an ultrasound-microbubble-mediated delivery system. This method yielded high expression of IMD in kidney cells. Renal IRI was induced by clamping the left renal artery followed by reperfusion. In response to IRI, overexpression of IMD in the kidney significantly improved renal function and pathology compared with the kidney transfected with control plasmid. We investigated the mechanisms by which IMD protects against renal IRI. We examined renal superoxide dismutase (SOD) activity and malondialdehyde (MDA) content and found SOD activity was significantly increased, while MDA level was markedly decreased in kidneys transfected with IMD, suggesting ROS production and oxidative stress were reduced by IMD overexpression. We also measured myeloperoxidase (MPO) activity, tubular cell apoptosis, and the expression of intercellular adhesion molecule-1 (ICAM-1), P-selectin, and endothelin-1 (ET-1) in the kidney. Renal MPO activity and the expression of ICAM-1, P-selectin, and ET-1 stimulated by IRI were significantly inhibited by IMD overexpression. Moreover, IMD overexpression prevented kidney cells from apoptosis caused by IRI. Our results demonstrate that overexpression of IMD in the kidney protects against renal IRI, apparently by reducing oxidative stress, consequently suppressing inflammation and vasoconstrictor production and apoptosis.

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Section: Discussionsupporting

confidence: 51%

Intermedin protects against renal ischemia-reperfusion injury by inhibition of oxidative stress

Qiao

Liu

et al. 2013

American Journal of Physiology-Renal Physiology

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“…This is consistent with the results of a previous study showing increased interleukin-8 levels and elevated numbers of neutrophilic granulocytes in the urine of DGF patients (Yarlagadda et al, 2008). The different perfusion intensities in different regions of the renal cortex suggest uneven distribution of resistance to renal microcirculation in DGF patients, which may be related to the pathological changes of terminal vasculature induced by ischemic reperfusion in the transplanted kidney (Inman et al, 2003;Huang et al, 2002). This may also be the mechanism of difference in the study by Angelescu et al (2003) (Figure 1).…”

Section: Discussionsupporting

confidence: 92%

“…Using a thermal dissipation probe inserted into the cortex of the transplanted kidney, Angelescu et al (2003) found lower microcirculatory perfusion in DGF patients than in patients with a normally functioning transplanted kidney. In addition, ischemic reperfusion has been shown to result in increased serum levels of endothelin and endothelin-1, but decreased levels of the vasodilator nitric oxide, which increases vascular resistance in the transplanted kidney (Schilling et al, 1996;Huang et al, 2002;Inman et al, 2003;Perico et al, 2004;Zlotnick et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Ultrasonic imaging characteristics of transplanted kidneys with delayed graft function

Liang¹,

Cai²,

Jiang³

et al. 2014

Genet. Mol. Res.

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ABSTRACT. We investigated the ultrasonic imaging characteristics of transplanted kidneys with delayed graft function (DGF). Ultrasonography was performed in 44 patients after kidney transplantation, and a time-intensity analysis was performed to compare the differences between patients with normal graft function (NGF) and those with DGF. Compared with the NGF group, the DGF group had earlier arrival time, shorter time to peak, and higher arrival intensity and peak intensity (P < 0.05). The variation-ofintensity parameters in different renal cortices increased, whereas the variation-of-time parameter decreased, in those with DGF (P < 0.05). In conclusion, compared with the NGF group, the microcirculation perfusion of transplanted kidneys in the DGF group showed higher perfusion with earlier arrival time, shorter time to peak, and higher arrival intensity and peak intensity. In addition, the 6879 ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 13 (3): 6878-6884 (2014) Ultrasonic imaging of delayed graft function intensity variations of contrast agent in different renal cortices from patients with DGF were greater, whereas the variations in perfusion time were smaller than those in patients with NGF.

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“…The major drawback of most reports, however, is the fact, that ERAs were administrated prior to and during the ischaemic period. Later application during the reflow period was ineffective in most cases [73–77]. Importantly, the dual ET receptor antagonist tezosentan has recently been shown to prevent the rise in serum creatinine as well as tubular necrosis, and to improve inulin clearance even when administrated after ischaemia [71], suggesting that dual ERA may be potentially useful in the clinical setting.…”

Section: Role Of Endothelin In the Pathophysiology Of Acute Renal Faimentioning

confidence: 99%

Role of endothelin and endothelin receptor antagonists in renal disease

Neuhofer¹,

Pittrow²

2006

Eur J Clin Investigation

108

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Endothelin (ET)-1 is a potent vasoconstrictor peptide with pro-inflammatory, mitogenic, and pro-fibrotic properties that is closely involved in both normal renal physiology and pathology. ET-1 exerts a wide variety of biological effects, including constriction of cortical and medullary vessels, mesangial cell contraction, stimulation of extracellular matrix production, and inhibition of sodium and water reabsorption along the collecting duct, effects that are primarily mediated in an autocrine/paracrine manner. Increasing evidence indicates that the ET system is involved in an array of renal disorders. These comprise chronic proteinuric states associated with progressive glomerular and tubulointerstitial fibrosis, including diabetic and hypertensive nephropathy, glomerulonephritis and others. In addition, ET-1 is causally linked to renal disorders characterized by increased renal vascular resistance, including acute ischaemic renal failure, calcineurin inhibitor toxicity, endotoxaemia, hepatorenal syndrome and others. Furthermore, derangement of the ET system may be involved in conditions associated with inappropriate sodium and water retention; for example, in congestive heart failure and hepatic cirrhosis. Both selective and non-selective ET receptor antagonist have been developed and tested in animal models with promising results. As key events in progressive renal injury like inflammation and fibrosis are mediated via both ET(A) and ET(B) receptors, while constrictor effects are primarily transduced by ET(A) receptors, dual ET receptor blockade may be superior over selective ET(A) antagonism. Several compounds have been developed with remarkable effects in several models of acute and progressive renal injury. Thus, clinical studies are required to assess whether these results can be confirmed in humans, hopefully leading to novel and effective therapeutic options with few side effects.

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The effect of endothelin antagonists on renal ischaemia-reperfusion injury and the development of acute renal failure in the rat

Abstract: The data show that both the ET(A)/ET(B) and selective ET(A)-receptor antagonist ameliorated the ischaemia-reperfusion injury when given in the peri-ischaemic period but not when the ET(A)-receptor antagonist was given for 60 min at 100 micro g/kg/min after the ischaemic period.

Cited by 26 publications

References 15 publications

Intermedin protects against renal ischemia-reperfusion injury by inhibition of oxidative stress

Intermedin protects against renal ischemia-reperfusion injury by inhibition of oxidative stress

Ultrasonic imaging characteristics of transplanted kidneys with delayed graft function

Role of endothelin and endothelin receptor antagonists in renal disease

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