Pretreatment of sildenafil attenuates ischemia-reperfusion renal injury in rats

被引：100

作者：

Choi, Dae Eun ^{[1
]}

Jeong, Jin Young ^{[1
]}

Lim, Beom Jin ^{[2
]}

Chung, Sarah ^{[1
]}

Chang, Yoon Kyung ^{[3
]}

Lee, Sang Ju ^{[3
]}

Na, Ki Ryang ^{[1
]}

Kim, Seok Young ^{[3
]}

Shin, Young Tai ^{[1
]}

Lee, Kang Wook ^{[1
]}

机构：

[1] Chungnam Natl Univ Hosp, Taejon, South Korea

[2] Gangnam Severance Hosp, Seoul, South Korea

[3] Daejeon St Mary Hosp, Taejon, South Korea

来源：

AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY | 2009年 / 297卷 / 02期

关键词：

apoptosis; ERK; NITRIC-OXIDE SYNTHASE; PHOSPHODIESTERASE-5; INHIBITION; ISCHEMIA/REPERFUSION INJURY; HYPOXIA/REOXYGENATION INJURY; HEART-FAILURE; KIDNEY; APOPTOSIS; CARDIOPROTECTION; TRANSPLANTATION; ACTIVATION;

D O I：

10.1152/ajprenal.90609.2008

中图分类号：

Q4 [生理学];

学科分类号：

071003 ;

摘要：

Choi DE, Jeong JY, Lim BJ, Chung S, Chang YK, Lee SJ, Na KR, Kim SY, Shin YT, Lee KW. Pretreatment of sildenafil attenuates ischemia-reperfusion renal injury in rats. Am J Physiol Renal Physiol 297: F362-F370, 2009. First published May 27, 2009; doi:10.1152/ajprenal.90609.2008.-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 IR groups. In study 2, we divided the rats into two groups: sildenafil-treated IR rats and PD98059 (ERK inhibitor) + sildenafil-treated IR 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 IR rats. The expression of inducible (iNOS) and endothelial nitric oxide synthase (eNOS) proteins in sildenafil-treated IR rats was significantly higher than in vehicle-treated IR rats. Pretreatment with sildenafil in IR rats increased ERK phosphorylation and reduced the renal Bax/Bcl-2 ratio, renal caspase-3 activity, and terminal dUTP nick end-labeling-positive 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 IR renal injury via ERK phosphorylation, induction of iNOS and eNOS production, and a decrease in the Bax/Bcl-2 ratio.

引用

页码：F362 / F370

页数：9

共 47 条

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