Bibliographic Details
| Title: |
Pretreatment of sildenafil attenuates ischemia-reperfusion renal injury in rats. |
| Authors: |
Dae Eun Choi, Jin Young Jeong, Beom Jin Lim, Chung, Sarah, Yoon Kyung Chang, Sang Ju Lee, Xi Ryang Na, Seok Young Kim, Young Tai Shin, Kang Wook Lee |
| Superior Title: |
American Journal of Physiology: Renal Physiology; Aug2009, Vol. 297, pF362-F370, 9p, 7 Graphs |
| Subject Terms: |
SILDENAFIL, ISCHEMIA treatment, TREATMENT of reperfusion injuries, KIDNEY disease treatments, SPRAGUE Dawley rats, NITRIC oxide, PHOSPHORYLATION, THERAPEUTICS |
| Abstract: |
Sildenafil was the first selective inhibitor of phosphodiesterase-5 (PDE5) to be widely used for treating erectile dysfunction. Many recent studies have investigated the cardioprotective role of sildenafil in animal models. We evaluated the protective effects of sildenafil in experimental renal ischemia-reperfusion (IR) injury in two studies. In study 1, male Sprague-Dawley rats were divided into four groups: sham, sildenafil-treated sham, vehicle-treated IR, and sildenafil-treated JR groups. In study 2, we divided the rats into two groups: sildenafil-treated JR rats and PD98059 (ERK inhibitor)+sildenafil-treated JR rats. Functional parameters of the kidney were evaluated at the molecular and structural levels. Blood urea nitrogen (BUN) and serum creatinine levels were lower in sildenafil-treated IR rats than in vehicle-treated JR rats. The expression of inducible (iNOS) and endothelial nitric oxide synthase (eNOS) proteins in sildenafil-treated JR rats was significantly higher than in vehicle-treated JR rats. Pretreatment with sildenafil in JR rats increased ERK phosphorylation and reduced the renal Bax/BcI-2 ratio, renal caspase-3 activity, and terminal dUTP nick end-labelingpositive apoptotic cells. In contrast, PD98059 treatment increased BUN and serum creatinine levels and attenuated the sildenafil-induced expression of pERK, iNOS, eNOS, and Bcl-2. PD98059 also increased caspase-3 activity but did not decrease the sildenafil-induced accumulation of cGMP. In conclusion, this study suggests that sildenafil has antiapoptotic effects in experimental JR renal injury via ERK phosphorylation, induction of iNOS and eNOS production, and a decrease in the BaxlBcl-2 ratio. [ABSTRACT FROM AUTHOR] |
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| Database: |
Complementary Index |
