Regulation of the Renal Endothelin System in the Two-Kidney, One Clip Renal Hypertensive Rat

Diekmann, Fritz; Zart, Rüdiger; Thöne-Reineke, Christa; Bauer, Christian; Neumayer, Hans‐Hellmut; Hocher, Berthold

doi:10.1097/00005344-200036001-00058

Cited by 6 publications

(9 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To understand, in some details, the molecular mechanisms involved in the up‐regulation of ET A and ET B2 receptors, we tested two specific inhibitors: one was MG‐132 (0.2, 1, 5 μM), an ubiquitin–proteasome inhibitor , which is capable of suppressing IκBα phosphorylation and degradation and subsequently inhibiting NF‐κB nuclear translocation , and the other was BMS345541, a highly selective IκBα inhibitor that inhibits the catalytic subunits of IκB kinase (IKK)‐1 and IKK‐2 and blocks NF‐κB‐mediated gene transcription .…”

Section: Resultsmentioning

confidence: 99%

“…This suggests that inhibition of IκBα phosphorylation leads to down‐regulation of the ET B2 receptors, while down‐regulation of the ET A receptors requires inhibition of both phosphorylation and ubiquitination of IκB. Increased expression of the endothelin receptors in the renal smooth muscle cells together with increased level of ET‐1 in blood during renal ischaemia might have a synergistic effect on the pathogenesis of renal vascular disease.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Nuclear Factor‐kappaB‐Mediated Endothelin Receptor Up‐Regulation Increases Renal Artery Contractility in Rats

Xie

Wang

Zhang

et al. 2013

Basic Clin Pharma Tox

View full text Add to dashboard Cite

Increased renal artery contractility leads to renal vasospasm and ischaemia as well as kidney damage. This study was designed to examine the hypothesis that organ culture of renal arteries induces transcriptional up-regulation of endothelin type A (ET A ) and type B2 (ET B2 ) receptors in the smooth muscle cells via activation of nuclear factor-kappaB (NF-jB) and subsequently increases renal artery contractility. Rat renal artery segments were organ-cultured for 6 or 24 hr to increase endothelin receptor-mediated contraction. To dissect molecular mechanisms involved in this process, inhibitors for NF-jB signalling pathway (MG-132 and BMS345541), transcription (actinomycin D) and translation (cycloheximide) were used during organ culture. Endothelin receptors were studied using a sensitive myograph (functional contractility), real-time PCR (mRNA analysis) and immunohistochemistry (protein localization). Compared with fresh segments, contractile responses to endothelin-1 (non-selective endothelin receptor agonist) and sarafotoxin 6c (selective ET B receptor agonist) were significantly increased in the segments after 24 hr of organ culture; ET B2 receptor-mediated maximal contraction increased from 2.7 AE 0.5 to 135.3 AE 5.1 (p < 0.001), and potency (pEC 50 ) of ET A receptor agonist increased from 8.20 AE 0.04 to 8.72 AE 0.07 (p < 0.001). This was in parallel with increased corresponding mRNA and protein expression for ET A and ET B2 receptors. BMS345541, MG-132, actinomycin D or cyclohexamide, respectively, suppressed the up-regulation of ET A and ET B2 receptors. Immunostaining performed with specific antibody showed that IjB was phosphorylated during organ culture. In conclusion, activation of NF-jB mediates up-regulation of ET A and ET B2 receptors and subsequently increases renal artery contractility, which may contribute to renal vasospasm and ischaemia as well as kidney damage.Increased renal vascular contractility and resistance trigger a cascade of events that lead to reduced renal blood flow, renal ischaemia and dysfunction, and even structural injury of kidney [1,2]. This cascade is often seen in endotoxaemic shockinduced renal ischaemia [3,4], renal artery stenosis [1] and severe renal artery spasm after blunt abdominal trauma [5], percutaneous transluminal renal angioplasty [6] and abdominal neuroblastoma removal [7]. However, the underlying molecular mechanisms that are responsible for the increased renal artery contractility and reduced renal blood flow are still not fully understood. Fenhammar et al. [4] reported that treatment with the dual endothelin receptor antagonist tezosentan in a porcine model of endotoxaemic shock attenuates the reduction of renal microcirculation and total renal blood flow, suggesting that endothelin-1 (ET-1) and its receptors are involved in the renal ischaemia. A recent study demonstrates that ET-1 released during endotoxaemia acts via endothelin type A (ET A ) receptors to impair renal blood flow and cause acute kidney injury [3]. To provide novel knowledge a...

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Nuclear Factor‐kappaB‐Mediated Endothelin Receptor Up‐Regulation Increases Renal Artery Contractility in Rats

Xie

Wang

Zhang

et al. 2013

Basic Clin Pharma Tox

View full text Add to dashboard Cite

show abstract

“…In this model, benefits of ET A antagonism are not apparent. In the clipped kidney, ET A in the renal medulla are up-regulated, 91 however, fibrotic atrophy is enhanced by ET A antagonism. 92 This suggests that a minimum degree of renal perfusion is required for ET A blockade to be beneficial rather than deleterious in CKD.…”

Section: One-clip Goldblatt Modelmentioning

confidence: 96%

Endothelin in Nondiabetic Chronic Kidney Disease: Preclinical and Clinical Studies

Culshaw

MacIntyre

Dhaun

et al. 2015

Seminars in Nephrology

View full text Add to dashboard Cite

“…Rats were anesthetized with intraperitoneally injection of ketamine hydrochloride (60 mg/kg) and xylazine (7.5 mg/kg) and underwent left renal artery constriction with a silver clip (internal gap of 0.20 mm) as described previously (Kunes 1993;Diekmann et al 2000;Nystrom et al 2002). In sham-clipped group, the same procedure was done without using silver clip.…”

Section: Preparation Of 2k1c Hypertensive Ratsmentioning

confidence: 99%

Effect of hypertension and its reverse on serum nitric oxide concentration and vascular permeability in two-kidney one-clip hypertensive rats

Khazaei¹,

Zarei²,

Sharifi³

et al. 2011

gpb

View full text Add to dashboard Cite

Abstract. The aim of this study was to evaluate the effect of hypertension and its reverse on serum nitric oxide (NO) concentration and endothelial permeability in two-kidney one-clip (2K1C) hypertensive rats. 28 male Wistar rats were divided into four groups: 1) 2K1C for 12 weeks; 2) sham-clipped for 12 weeks; 3) 2K1C for 12 weeks and unclipped for 12 weeks; 4) sham-clipped for 12 weeks and unclipped for 12 weeks. Blood samples were taken before experiment, 12 th week and 24 th week (in groups 3 and 4). Coronary vascular and aortic endothelial permeability were determined by extravasation of Evans blue dye method. Serum NO level was significantly lower in hypertensive group compare with sham group (4.21 ± 1.28 vs. 9.47 ± 1.34 µmol/l, respectively). Reversal of hypertension did not improve serum NO concentration in 2K1C group (4.21 ± 1.28 vs. 4.32 ± 1.34 µmol/l). Coronary vascular and aortic endothelial permeability were not different between hypertensive and normotensive groups and reversal of hypertension did not alter endothelial permeability. Lower serum NO concentration in 2K1C hypertensive rats even after reversal of hypertension suggested that in addition to NO, other mechanisms could be involved in surgical reversal of hypertension. Hypertension and its reverse did not change endothelial permeability at least in this model of hypertension.

show abstract

Regulation of the Renal Endothelin System in the Two-Kidney, One Clip Renal Hypertensive Rat

Cited by 6 publications

References 0 publications

Nuclear Factor‐kappaB‐Mediated Endothelin Receptor Up‐Regulation Increases Renal Artery Contractility in Rats

Nuclear Factor‐kappaB‐Mediated Endothelin Receptor Up‐Regulation Increases Renal Artery Contractility in Rats

Endothelin in Nondiabetic Chronic Kidney Disease: Preclinical and Clinical Studies

Effect of hypertension and its reverse on serum nitric oxide concentration and vascular permeability in two-kidney one-clip hypertensive rats

Contact Info

Product

Resources

About