Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.
Department of Urology, First People's Hospital of Xiaochang County, Hubei, China.
J Cell Mol Med. 2020 Dec;24(24):14280-14292. doi: 10.1111/jcmm.16045. Epub 2020 Oct 29.
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.
探讨 5 型磷酸二酯酶（PDE5）信号通路的改变以及氧化应激与自发性高血压大鼠（SHR）海绵体平滑肌（CCSM）中松弛和收缩分子的表达变化与勃起功能障碍（ED）的相关性。在这项研究中，使用了 SHR 和 Wistar-Kyoto（WKY）大鼠。通过阿扑吗啡试验和海绵体神经电刺激（ES）来确定勃起功能。进行了马松三色染色和共聚焦显微镜检查。通过 RT-PCR 和 Western blot 测定了一氧化氮合酶（NOS）、PDE5、磷酸化-PDE5 和 α1-肾上腺素能受体（α1AR），而通过比色分析测定了 CC 中的氧化应激。SHR 表现出明显的 ED。SHR 的 CC 显示 SM 减少但胶原纤维增多。NOS 同工型在 SHR 中的表达明显降低，而所有 α1AR 同工型均增加。此外，在高血压大鼠中，PDE5 和磷酸化-PDE5 下调，其活性减弱。同时，SHR 组发生氧化应激，这可能受内质网应激和 NADPH 氧化酶上调调节。CC 中的 NOS 和 α1AR 失调、组织学变化和氧化应激可能与高血压引起的 ED 的病理生理学有关。此外，PDE5 下调可能导致某些高血压 ED 患者 PDE5 抑制剂的疗效降低，而氧化应激的治疗可以作为这种 ED 的新治疗靶点。
