Effect of Ketanserine in Cyclosporine-lnduced Renal Dysfunction in Rats

Darlametsos, I.; Morphake, P.; Bariéty, J; Hornych, A; Tsipas, G.; Gkikas, G.; Papanikolaou, Nikolaos

doi:10.1159/000188592

Cited by 15 publications

(8 citation statements)

References 26 publications

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“…In this model we investigated a potential protection by levemopamil (L), a calcium channel blocker with 5-HT (5-HT2) receptor antagonist activity (Hofmann et al, 1989). This drug has been shown previously in rats to preserve the function of the transplanted kidney following warm and cold ischaemia (Mills et al, 1987) or to protect the kidney from cyclosporine-induced damage (Darlametsos et al, 1995). It also reduced infarct size following cerebral artery occlusion (Nakayama et al, 1988).…”

Section: Discussionmentioning

confidence: 90%

“…More recently, 5-HT was demonstrated to be a potent vasoconstrictor in the kidney (Endlich et al, 1993) and also to play a pathogenetic role in acute clinical (Sidel'nikov & Sivoraksha, 1990) and experimental renal damage (Darlametsos et al, 1995). 5-HT is released from enterochromaffin cells and, more importantly, from platelets, but may also be produced in proximal tubule cells (Sole et al, 1986).…”

Section: Discussionmentioning

confidence: 99%

“…That 5-hydroxytryptamine (5-HT) plays a role in the regulation of renal haemodynamics via 5-HT2 receptors has been demonstrated by various authors Endlich et al, 1993). The potential role of 5-HT in acute renal damage has been studied in the rat kidney after transplantation following warm and cold ischaemia (Mills et al, 1987) as well as following cyclosporine administration (Darlametsos et al, 1995). A pathogenic role of 5-HT was suggested in patients with haemorrhagic fever and ARF (Sidel'nikov & Sivoraksha, 1990).…”

Section: Introductionmentioning

confidence: 99%

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Calcium entry and 5‐HT₂ receptor blockade in oliguric ischaemic acute renal failure: effects of levemopamil in conscious rats

Kramer

Rosberg

Bäcker

et al. 1996

British J Pharmacology

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1 Unilateral left renal artery occlusion for 1 h in a group of 8 untreated female Sprague-Dawley rats resulted in oliguric acute renal failure (ARF) persisting for more than 6 h after reflow, i.e. after reperfusion of the kidney by removal of the arterial clamp. In a second group of 8 rats with left unilateral ARF the effects of levemopamil (L), a calcium entry blocker with 5-hydroxytryptamine2 (5-HT2) receptor antagonistic properties, were studied. Rats received L as a continuous infusion (6 mg kg-' h-') from 1 h before ischaemia until 6 h after reflow. 2 Endogenous creatinine clearance, an estimate of glomerular filtration rate (GFR), of left ischaemic kidneys of untreated rats was almost completely abolished and urine flow was 0.05 + 0.02 and 0.03 + 0.01 ml h'-100 g' body weight (body wt.) at 2 and at 6 h of reflow, respectively. In contrast, left ischaemic kidneys of L-treated rats revealed significantly higher GFR (0.10 + 0.02 and 0.03+0.01 mlmin-' g kidney weight (k.wt.); P<0.01) and urine flow (0.51+0.05 and 0.15 +0.04 ml h-' 100 g' body wt.; P<0.05) at 2 and 6 h of reflow, respectively. 3 At 6 h of reflow, mitochondria from the cortex of left ischaemic kidneys of untreated rats showed significantly reduced ATP synthesis when compared to right intact kidneys (0.06 + 0.02 vs 0.26+0.02 ymol ATP mg-' protein min-' (P<0.01)). In contrast, in L-treated rats, ATP synthesis of left ischaemic kidneys was largely preserved (0.17+0.01 ymol ATP mg-' protein min-').4 Ischaemia of left kidneys resulted in a significant decrease in medullary Na-K-ATPase activity to 9.6+2.4 as compared to 20.4+3.7 ,umol Pi h-' mg-' protein in the intact right kidneys which was not prevented by L (9.4+2.4 ymol Pi h-' mg-' protein).5 In untreated rats the calcium content in cortical mitochondria from left ischaemic kidneys had risen 2 fold to 23.0+1.8 at 6 h of reflow as compared to 12.2 + 0.3 nmol mg-' protein in right intact kidneys (P<0.01). This rise in mitochondrial calcium was not significantly attenuated by treatment with L (19.9 + 1.7 nmol mg'-protein). 6 The results show that L transiently converted oliguria into non-oliguria during the early phase after reflow in ischaemic ARF, i.e. after reperfusion following 1 h of complete interruption of renal perfusion. The present data suggest indirectly that the 5-HT2-antagonistic properties of L rather than its calcium channel blocking action maintains GFR at low level and protects mitochondrial function early after reflow in this model of ischaemic ARF.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Calcium entry and 5‐HT₂ receptor blockade in oliguric ischaemic acute renal failure: effects of levemopamil in conscious rats

Kramer

Rosberg

Bäcker

et al. 1996

British J Pharmacology

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“…Our data clearly indicated that urinary TxB 2 was lower in both the normal and postischaemic kidney of WF rats, whereas excretion of the vasodilator PGE 2 , the main prostanoid in the kidney, was similarly increased in both WH and WF rats. The ratio between vasodilator (PGE 2 ) and vasoconstrictor (TxA 2 ) autacoids, which is routinely used as an indicator of the direct role of vasoconstrictor factors in the development of renal failure, [52][53][54] appeared to be higher in WF than WH rats after I/R. Interestingly, COX-2 activity has been reported to depend on nNOS activity.…”

Section: Discussionmentioning

confidence: 99%

Protection of Wistar‐Furth rats against postischaemic acute renal injury: Role for nitric oxide and thromboxane?

Voisin

Declèves

Hubert

et al. 2014

Clin Exp Pharma Physio

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The Wistar-Furth (WF) rat strain is usually used in models of full major histocompatibility complex-mismatched kidney transplantation. Because these rats have been demonstrated to be resistant to several models of chronic kidney disease, the aim of the present study was to investigate their potential resistance to renal ischaemia-reperfusion (I/R) injury compared with another strain, namely Wistar-Hanover (WH) rats. Anaesthetized male WH and WF rats were submitted to I/R by occlusion of the left renal artery and contralateral nephrectomy. Urine, blood and tissue samples were collected at different time points after I/R to evaluate renal function, inflammation and tubular injury, along with determination of nitric oxide synthase (NOS) expression and thromboxane A2 (TxA2 ) production. Post-ischaemic renal function was better preserved in WF than WH rats, as evidenced by reduced levels of creatininaemia, urinary neutrophil gelatinase-associated lipocalin excretion and proteinuria. In addition, WF rats had less intrarenal inflammation than WH rats after I/R injury. These observations were associated with maintenance of neuronal NOS expression, along with lower induction of inducible NOS expression in WF versus WH rats. Moreover, WF rats excreted a significantly lower amount of TxB2 . The results indicate that WF rats are more resistant to an I/R injury than WH rats in terms of renal function and inflammation. These observations are associated with differential regulation of intrarenal NOS expression, as well as a reduction in thromboxane production, which could contribute to a better outcome for the postischaemic kidney in WF rats.

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“…[1,2] CsA nephrotoxicity is characterized by intense renal vasoconstriction that induces a fall in renal blood flow and in the glomerular filtration rate. Morphological changes to the kidney, consisting of tubular diffusion vacuolization, single-cell necrosis, [9] and microcalcification are fully reversible. However, even with normal blood levels or during long-term dosage, CsA can produce chronic hypertension and can be the cause of irreversible impairment of renal function.…”

Section: Introductionmentioning

confidence: 99%

Nifedipine Attenuates Changes in Nitric Oxide Levels, Renal Oxidative Stress, and Nephrotoxicity Induced by Cyclosporine

Chander¹,

Chopra²

2005

LRNF

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Cyclosporine A (CsA) is a potent and effective immunosuppressive agent, but its action is frequently accompanied by severe renal toxicity. The causes for the nephrotoxicity of CsA have not been fully elucidated. Intrarenal vasoconstriction induced by several different mediators, both in humans and experimental animals, have been proposed. To determine if the renal alterations are mediated directly by cyclosporine or by secondary hemodynamic alterations induced by cyclosporine, we evaluated if nifedipine prevents these alterations. Eight groups of rats were employed in this study, group 1 served as control, group 2 rats were treated with CsA (20 mg/mL, s.c. for 21 days), groups 3, 4, and 5 received CsA along with various doses of nifedipine (5, 10, and 20 mg/kg, p.o.) 24 h before and 21 days concurrently, groups 6, 7, and 8 received L-NAME (10 mg/kg i.p.), propranolol (10 mg/kg i.p.), and aminoguanidine (100 mg/kg p.o.), respectively, along with CsA. Renal function was assessed by measuring serum creatinine, blood urea nitrogen, creatinine, and urea clearance. Tissue and urine nitrite and nitrate levels were measured to estimate the total nitric oxide levels. The renal oxidative stress was measured by renal malondialdehyde levels, reduced glutathione levels, and enzymatic activity of catalase and superoxide dismutase. Renal morphological alterations were assessed by histopathological examination. CsA administration for 21 days resulted in a marked renal oxidative stress, and significantly deranged the renal functions as well as renal morphology. Treatment with nifedipine (10, 20 mg/kg) significantly improved the renal dysfunction, tissue and urine total nitric oxide levels, and renal oxidative stress and prevented the alterations in renal morphology. These results clearly demonstrate that nifedipine is beneficial as a protective agent against nephrotoxicity induced by CsA, and the protection afforded by nifedipine appears to be mediated by an increase in endothelial nitric oxide release.

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Effect of Ketanserine in Cyclosporine-lnduced Renal Dysfunction in Rats

Cited by 15 publications

References 26 publications

Calcium entry and 5‐HT₂ receptor blockade in oliguric ischaemic acute renal failure: effects of levemopamil in conscious rats

Calcium entry and 5‐HT₂ receptor blockade in oliguric ischaemic acute renal failure: effects of levemopamil in conscious rats

Protection of Wistar‐Furth rats against postischaemic acute renal injury: Role for nitric oxide and thromboxane?

Nifedipine Attenuates Changes in Nitric Oxide Levels, Renal Oxidative Stress, and Nephrotoxicity Induced by Cyclosporine

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Effect of Ketanserine in Cyclosporine-lnduced Renal Dysfunction in Rats

Cited by 15 publications

References 26 publications

Calcium entry and 5‐HT2 receptor blockade in oliguric ischaemic acute renal failure: effects of levemopamil in conscious rats

Calcium entry and 5‐HT2 receptor blockade in oliguric ischaemic acute renal failure: effects of levemopamil in conscious rats

Protection of Wistar‐Furth rats against postischaemic acute renal injury: Role for nitric oxide and thromboxane?

Nifedipine Attenuates Changes in Nitric Oxide Levels, Renal Oxidative Stress, and Nephrotoxicity Induced by Cyclosporine

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Calcium entry and 5‐HT₂ receptor blockade in oliguric ischaemic acute renal failure: effects of levemopamil in conscious rats

Calcium entry and 5‐HT₂ receptor blockade in oliguric ischaemic acute renal failure: effects of levemopamil in conscious rats