PDE5 inhibition against acute renal ischemia reperfusion injury in rats: does vardenafil offer protection?

Kyriazis, Iason; Kagadis, George C.; Kallidonis, Panagiotis; Georgiopoulos, Ioannis; Marazioti, Antonia; Geronasiou, Aikaterini; Liourdi, Despoina; Loudos, George; Schinas, Vasilios; Apostolopoulos, Dimitris; Papadaki, Helen; Flordellis, Christodoulos S.; Nikiforidis, George; Papapetropoulos, Andreas; Liatsikos, Evangelos

doi:10.1007/s00345-012-0980-4

Cited by 15 publications

(10 citation statements)

References 12 publications

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“…The most notable changes in the ischemic kidney that can be seen by light microscopy are broad areas of necrosis, the most common in the cortico-medullary zone, brush border loss and a large number of PAS positive casts in the renal medulla [27], [29]. Morphological changes in the kidneys isolated from rats with induced ischemic ARF, exactly correspond to the previous description.…”

Section: Discussionsupporting

confidence: 84%

Losartan Improved Antioxidant Defense, Renal Function and Structure of Postischemic Hypertensive Kidney

Ivanov

Mihailović-Stanojević

Milanović

et al. 2014

PLoS ONE

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Ischemic acute renal failure (ARF) is a highly complex disorder involving renal vasoconstriction, filtration failure, tubular obstruction, tubular backleak and generation of reactive oxygen species. Due to this complexity, the aim of our study was to explore effects of Angiotensin II type 1 receptor (AT1R) blockade on kidney structure and function, as well as oxidative stress in spontaneously hypertensive rats (SHR) after renal ischemia reperfusion injury. Experiments were performed on anaesthetized adult male SHR in the model of ARF with 40 minutes clamping the left renal artery. The right kidney was removed and 40 minutes renal ischemia was performed. Experimental groups received AT1R antagonist (Losartan) or vehicle (saline) in the femoral vein 5 minutes before, during and 175 minutes after the period of ischemia. Biochemical parameters were measured and kidney specimens were collected 24h after reperfusion. ARF significantly decreased creatinine and urea clearance, increased LDL and lipid peroxidation in plasma. Treatment with losartan induced a significant increase of creatinine and urea clearance, as well as HDL. Lipid peroxidation in plasma was decreased and catalase enzyme activity in erythrocytes was increased after losartan treatment. Losartan reduced cortico-medullary necrosis and tubular dilatation in the kidney. High expression of pro-apoptotic Bax protein in the injured kidney was downregulated after losartan treatment. Our results reveal that angiotensin II (via AT1R) mediates the most postischemic injuries in hypertensive kidney through oxidative stress enhancement. Therefore, blockade of AT1R may have beneficial effects in hypertensive patients who have developed ARF.

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Section: Discussionsupporting

confidence: 84%

Losartan Improved Antioxidant Defense, Renal Function and Structure of Postischemic Hypertensive Kidney

Ivanov

Mihailović-Stanojević

Milanović

et al. 2014

PLoS ONE

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“…This promotes protein phosphorylation, cell growth, and survival giving protection against cellular injury (8,19). Kyrialzis et al found that the vardenafil, another selective PDE-5 inhibitor, administered immediately before reperfusion, did not improve renal function in an in situ renal warm ischemic rodent model (23). Sildenafil may also trigger other protective mechanisms independent of endothelial NO synthase and inducible NO synthase upregulation (22).…”

Section: Discussionmentioning

confidence: 99%

Sildenafil Citrate in a Donation After Circulatory Death Experimental Model of Renal Ischemia-Reperfusion Injury

Hosgood

Randle²,

Patel³

et al. 2014

Transplantation

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“…43,44 In addition, multiple studies proved that ERK activation was commonly protective in renal IRI. 44,45 By the contrast, IRI dramatically increased phosphorylated ERK1/2 expression and promoted apoptosis have also been reported. 46 In our present work, we found that the expression of phosphorylated ERK1/2 was significantly elevated which accompanied with renal function decrease at 24 h after ROSC in NS group.…”

Section: Discussionmentioning

confidence: 86%

<p>Edaravone Ameliorates Renal Warm Ischemia-Reperfusion Injury by Downregulating Endoplasmic Reticulum Stress in a Rat Resuscitation Model</p>

Zheng

et al. 2020

DDDT

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Background: This study was conducted to explore whether the effect of edaravone (5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol3-one, EDR) can ameliorate renal warm ischemia-reperfusion injury (IRI) by modulating endoplasmic reticulum stress (ERS) and its downstream effector after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) in a rat model. Methods: The rats (n=10) experienced anaesthesia and intubation followed by no CA inducement were defined as the Sham group. Transoesophageal alternating current stimulation was employed to establish 8 min of CA followed by conventional CPR for a resuscitation model. The rats with successful restoration of spontaneous circulation (ROSC) randomly received EDR (3 mg/kg, EDR group, n=10) or equal volume normal saline solution (the NS group, n=10). At 24 hr after ROSC, serum creatinine (SCR), blood urea nitrogen (BUN) levels, and cystatin-C (Cys-C) levels were determined and the protein level of glucose-regulated protein (GRP78), C/EBP homologous protein (CHOP), extracellular signal-regulated kinase (ERK), phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), Bax/Bcl-2, and caspase-3 were detected by Western blot method. Results: At 24 hrs after ROSC, SCR, BUN and Cys-C were obviously increased and the proteins expression, including GRP78, CHOP and p-ERK1/2, cleaved-caspase 3 Bax/Bcl-2 ratio, were significantly upregulated in the NS group compared with the Sham group (p<0.05). The remarkable improvement of these adverse outcomes was observed in the EDR group (p<0.05). Conclusion: In conclusion, we found that EDR ameliorates renal warm IRI by downregulating ERS and its downstream effectors in a rat AKI model evoked by CA/CPR. These data may provide evidence for future therapeutic benefits of EDR against AKI induced by CA/CPR.

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PDE5 inhibition against acute renal ischemia reperfusion injury in rats: does vardenafil offer protection?

Abstract: Vardenafil attenuates renal IRI. Based on similar results from relevant studies on other PDE-5 inhibitors in renal and cardiac IRI, it can be assumed that all PDE-5 inhibitors share a common mechanism of cytoprotection.

Cited by 15 publications

References 12 publications

Losartan Improved Antioxidant Defense, Renal Function and Structure of Postischemic Hypertensive Kidney

Losartan Improved Antioxidant Defense, Renal Function and Structure of Postischemic Hypertensive Kidney

Sildenafil Citrate in a Donation After Circulatory Death Experimental Model of Renal Ischemia-Reperfusion Injury

<p>Edaravone Ameliorates Renal Warm Ischemia-Reperfusion Injury by Downregulating Endoplasmic Reticulum Stress in a Rat Resuscitation Model</p>

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