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Alterations in the phosphodiesterase type 5 pathway and oxidative stress correlate with erectile function in spontaneously hypertensive rats
Authors:Weixiang He  Jianmin Liu  Daoquan Liu  Jundong Hu  Ye Jiang  Mingzhou Li  Qian Wang  Ping Chen  Guang Zeng  Deqiang Xu  Xinghuan Wang  Michael E. DiSanto  Xinhua Zhang
Affiliation:1. Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan China ; 2. Department of Urology, First People''s Hospital of Xiaochang County, Hubei China ; 3. Department of Urology, People''s Hospital of Qichun County, Hubei China ; 4. Department of Surgery and Biomedical Sciences, Cooper Medical School of Rowan University, Camden NJ, USA
Abstract:To explore how alterations in the phosphodiesterase type 5 (PDE5) signalling pathway and oxidative stress correlate with changes in the expression of relaxation and contraction molecules and erectile dysfunction (ED) in the corpus cavernosum smooth muscle (CCSM) of spontaneously hypertensive rats (SHR). In this study, SHR and Wistar‐Kyoto (WKY) rats were used. Erectile function was determined by apomorphine test and electrical stimulation (ES) of cavernous nerve. Masson''s trichrome staining and confocal microscopy were performed. Nitric oxide synthase (NOS), PDE5, phosphorylated‐PDE5 and α1‐adrenergic receptor (α1AR) were determined by RT‐PCR and Western blotting while oxidative stress in CC was determined by colorimetric analysis. SHR exhibited obvious ED. CC of SHR showed less SM but more collagen fibres. The expression of NOS isoforms in SHR was significantly decreased while all α1AR isoforms were increased. In addition, PDE5 and phosphorylated‐PDE5 were down‐regulated and its activity attenuated in the hypertensive rats. Meanwhile, the SHR group suffered oxidative stress, which may be modulated by endoplasmic reticulum stress and NADPH oxidase up‐regulation. Dysregulation of NOS and α1AR, histological changes and oxidative stress in CC may be associated with the pathophysiology of hypertension‐induced ED. In addition, PDE5 down‐regulation may lead to the decreased efficacy of PDE5 inhibitors in some hypertensive ED patients and treatment of oxidative stress could be used as a new therapeutic target for this type of ED.
Keywords:corpus cavernosum   erectile dysfunction   hypertension   oxidative stress   phosphodiesterase type 5   spontaneously hypertensive rats
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