Literature DB >> 23143734

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

Iason Kyriazis1, George C Kagadis, Panagiotis Kallidonis, Ioannis Georgiopoulos, Antonia Marazioti, Aikaterini Geronasiou, Despοina Liourdi, George Loudos, Vasilios Schinas, Dimitris Apostolopoulos, Helen Papadaki, Christodoulos Flordellis, George C Nikiforidis, Andreas Papapetropoulos, Evangelos Nu Liatsikos.   

Abstract

PURPOSE: To evaluate the effect of vardenafil on renal function after renal ischemia-reperfusion (IR) injury (IRI) in a rat model.
MATERIALS AND METHODS: Seventy-one Wistar rats were divided into 7 groups including (1) a vehicle-treated group, (2) a vehicle pretreated-IR group, (3-6) vardenafil pretreated-IR groups in doses of 0.02, 0.2, 2 and 20 μg/kg, respectively, (7) a group of IR followed by treatment with 2 μg/kg of vardenafil. Vardenafil or vehicle solution was administered one hour before unilateral nephrectomy and the induction of 45 min of ischemia on the contralateral kidney by clamping of renal pedicle. Four hours of reperfusion were allowed after renal ischemia. Studied parameters were serum creatinine, fractional excretion of sodium (FENa), and histological evaluation of renal specimens. In addition, renal tissue cGMP levels, ERK1/2 phosphorylation as well as renal function by renal scintigraphy were also evaluated.
RESULTS: Administration of vardenafil before the induction of ischemia resulted in a significant reduction in creatinine and FENa levels as well as in less histological lesions observed in treated kidneys in comparison with the vehicle-treated group. The underlying mechanism of cytoprotection was cGMP depended and involved the phosphorylation of ERK proteins. Renal scintigraphy confirmed that PDE5 inhibition attenuates renal IRI.
CONCLUSIONS: 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.

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Year:  2012        PMID: 23143734     DOI: 10.1007/s00345-012-0980-4

Source DB:  PubMed          Journal:  World J Urol        ISSN: 0724-4983            Impact factor:   4.226


  11 in total

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